Jumat, 01 Juli 2011

Buah Sirsak dapat menyembuhkan penyakit Colestelor


Sirsak

(Annona muricata, Linn. (Latin))

Sinonim :
--

Familia :
Annonaceae

Ditulis Oleh : Tjung teck
Buah Sersak dapat menyembuhkan penyakit Colestelor karena banyak mengandung zat asam yang tinggi dan ini ternyata bisa di konsumsi setiap hari menurunkan atau membersikan minyak darah dalam Altereli dalam saluran darah.

Sersak juga dapat di peroleh di mana saja dan ini merupakan ciri khas aneka buah-buahan yang baik dalam makanan yang terkandung di dalamnya berupa vitamin c dan asam Amino,B1 dan vitamin yg lain yang terkandung di dalamnya dan zar serat yang tinggi yang terapat di dalam buah sersak ini yang sehingga bisa mengobati berbagi penyakit seperti,bisul,sakit pinggang,Ambaein,kangker,tomor,penyakit kantung keni,anak menceret,dan sebagianya itu,akan tetapi buah sersak ini juga merupakan suatu konsumsi bentuk minuman beraneka ragam jus dalam bentuk muniman yang sangat menyegarkan dahaga diwaktu terik matahari yang panas,buah sersak ini juga berguna untuk menurunkan colestelor dimana telalu banyak makan yang berlebihan seperti minyak,gorengan,daging,siput,udang,ikan,cumi-cumi,makan laut,dan sebaginya yang sehingga menimbulkan penyakit yang menyerang tiba-tiba seperti halnya serangan jantung akibat colestelor yang tinggi dengan makan yang tidak teratur dengan banyak makan yang berlemak dan kurang olah raga,sehingga resiko terserang penyakit jantung pun bisa terjadi di setiap saat,jadi untuk menjaga kesehatan akan tubuh manusia ini dengan juga banyak mengurangi makan yang mengandung lemak dan siput makanan laut,lebih banyak makan sayuran dan buah-buhan yang mengandung berbagai vitamin di dalamnya,banyak berolah raga,kurangi makan yang gorengan dan pedas ini merupakan faktor penunjang hidup sehat.

Sirsak (Annona muricata) berupa tumbuhan atau potion yang berbatang utama berukuran kecil dan rendah. Daunnya berbentuk bulat telur agak tebal dan pada permukaan bagian atas yang halus berwarna hijau tua sedang pada bagian bawahnya mempunyai warna lebih muda. Tumbuhan ini dapat tumbuh di sembarang tempat. Tetapi untuk memperoleh hasil buah yang banyak dan besar-besar, maka yang paling balk ditanam di daerah yang tanahnya cukup mengandung air. Di Indonesia, sirsak tumbuh dengan baik pada daerah yang mempuyai ketinggian kurang dari 1000 meter di atas permukaan laut. Nama Sirsak itu sendiri sebenarnya berasal dari bahasa Belanda Zuurzak yang kuranglebih berarti kantung yang asam. Buah Sirsak yang sudah masak lebih berasa asam daripada manis. Pengembangbiakan sirsak yang paling baik adalah melalui okulasi dan akan menghasilkan buah pada usia 4 tahunan setelah ditanam.

Orang sering terserang penyakit bisul yang merupakan akibat darah yang kurang bersih dengan banyak makan yang kurang bergizi atau tercermar oleh limbah kimia yang berlebihan dalam makanan baik sayuran,buahan,daging,ikan dan makan laut,sehingga darah menjadi tidak sehat dan tercemar oleh limbah itu,sehingga pertumbuhan badan dan metabolisme pun tergangu olehnya ,sehingga muncul penyakit berupa bisul,kanker,benjolan,dan pertumbuhan tubuh yang tidak normal mestinya,jadi banyak mengkomsumsi buah sersak bisa memperkecil resiko terserang penyakit tentunya jantung berupa colestelor ini.Setiap saat di waktu yang besamaan di mana menu makanan akan di sajikan di waktu makan pagi,siang,malam,dan ini bisa di sajikan dalam bentuk aneka minuman buah-buahan yang sangat menyegarkan,dengan menimun segelas sirsak maka colestelor juga bisa berkurang dari hasil makan yang berlebihan seperti makan yang benyak mengandung lemak,dan makanan laut itu.

Khasiat dan manfaat untuk pengobatan:

Ambeien
Bahan: buah sirsak yang sudah masak;
Cara membuat: diperas untuk diambil airnya sebanyak 1 gelas;
Cara menggunakan : diminum 2 kali sehari, pagi dan sore.

Sakit Kandung Air Seni
Bahan: buah sirsak setengah masak, gula dan garam secukupnya;
Cara membuat: semua bahan tersebut dimasak dibuat kolak;
Cara menggunakan : dimakan biasa, dan dilakukan secara rutin setiap hari selama 1 minggu berturut-turut.

Bayi Mencret
Bahan: buah-sirsak yang sudah masak;
Cara membuat: buah sirsak diperas dan disaring untuk diambil airnya;
Cara menggunakan : diminumkan pada bayi yang mencret sebanyak 2-3 sendok makan.

Anyang-anyangen (sering kecing tetapi sedikit dan terasa sakit)
Bahan: sirsak setengah masak dan gula pasir secukupnya;
Cara membuat: sirsak dikupas dan direbus dengan gula bersama-sama dengan air sebanyak 2 gelas; Cara menggunakan : disaring dan diminum.

Sakit Pinggang
Bahan: 20 lembar daun sirsak;
Cara membuat: direbus dengan 5 gelas air sampai mendidih hingga tinggal3 gelas;
Cara menggunakan : diminum 1 kali sehari 3/4 gelas.

Bisul
Bahan: daun sirsak yang masih muda secukupnya;
Cara membuat: ditumbuk halus dan ditambah 1/2 sendok air, diaduk sampai merata;
Cara menggunakan : ditempelkan pada bagian bisul.

Colestelor
Bahan: buah sersak yang masih muda secukupnya
Cara membuat:di jus buang bijiknya di tambah 1/2 sendok air,di aduk sampai rata dan gula secukupnya
Cara menggunakan : diminum berbentuk jus aneka minuman buah.
Dapat mengurangi resiko serangan jantung,kanker,tumor,benjolan
Cara menggunakan : diminum 2 kali sehari, pagi dan sore.

Wortel vitamin A untuk kesehatan Mata


Ditulis oleh : Tjung teck
Wortel Vitamin A untuk kesehatan Mata dan mengandung banyak Vitamin A dari setiap batang Wortel ini.

Wortel merupakan makan yang bergizi tinggi disaat kalau kita lihat setiap konsumsi setiap makan hidangan pagi hari,siang hari,malam hari ini bisa dijadikan makan yang sangat melejatkan setiap makan,seperti halanya di dalam kehidupan dimana disaat jamuan makan ini tiba maka setiap menu makanan juga terlihat wortel sangat dominan dalam setiap hidangan makanan ini,halnya dengan setiap perkembangan jaman terus menerus maka wortel juga sebagai minuman yang berciri khas tersendiri dari setiap hidangan minuman ini,kalau dalam menu makan wortel ini juga tersedia dalam bentuk makan seperti campuran telur yang wortel di iris dan di campurkan ke dalam telur dan di kocok menjadi satu sehingga juga di goreng dan menghasilakan telur dan wortel dalam bentuk sajian makanan pagi,siang maupun malam itu,wortel ini juga bisa di lihat setiap restoran,penjajah kaki lima,kedai buah-buahan,dan sebaginya itu,juga bisa menjajikan beraneka minuman yang tentunya dari wortel itu seperti halnya dengan segelas jug wortel yang segar itu,dan wortel ini juga pada jaman dahulu di belah hutan merupakan suatu ciri khas makanan hewan kelinci atau marmut yang merupakan makanan pokok kelinci itu,kalau jaman sekarang sudah banyak di ketemukan wortel ini di belahan dunia baik Asia dan Eropa sebagai sayuran dan buah-buahan,semua ini pun terdapat tentunya di daerah pertanian seperti di dearah yang dingin dan pergunungan atau dataran tinggi yang tanahnya subur dengan cuacar yang cukup untuk pertanian wortel ini,seperti kalau di Indonesia terdapat di daerah dataran tinggi seperti halnya di berastagi Medan,puncak di Bandung,dan sebaginya itu.

Disaat seseorang kekurangan akan vitamin A maka banyak mengkonsumsi wortel akan memperbaiki jaringan mata yang rusak akibat stress bagian bola mata karena banyak melihat buku misalnya,lelah melihat komputer,capek,dan lain-lain itu,namun semua itu juga dapat di teruskan dengan banyak melatih diri dengan kondisi mata yang lelah menjadi lebih semangat lagi,begitu juga disaat seorang terserang pemyakit mata seperti mata merah,mata bengkak dan sebaginya itu juga bisa membantu dengan pertumbuhan dari fase persembuhan dengan banyak mengkumsumsi wortel ini.

Dalam jurnal ISHS Acta Horticulturae 604 yang ditulis oleh M. Kleemann, W.J. Florkowski berjudul Bitternes of Carrot as Quality of Indicator disebutkan cita rasa pada wortel ditentukan oleh kandungan senyawa-senyawa terpena. Yaitu gula bebas, terpenoid yang mudah menguap, karbonil, fenolat, pyrazines and asam amino bebas. Senyawa-senyawa itu biasanya memberi cita rasa harum dan segar pada wortel. Tetapi pada konsentrasi tinggi, malah menyebabkan cita rasa yang tidak menyenangkan. Yang terakhir ini disebabkan oleh faktor genetika, kondisi penanaman, serangan hama dan serangga, penanganan pasca panen dan kondisi atmosfer penyimpanan.

Seperti halnya bisa di lihat dengan disaat setelah produksi wortel ini berjalan dengan disaat dari pencabutan dan di masukan dalam kerangjang atau di kemas dan di bawak ke kota atau pusat pasar dan di jual dengan keadaan yang segar disaat pagi hari kalau kita belanja dan melihat wortel yang indah dan sangat segar untuk di makan atau komsumsi dengan berbagai ragan cara masakan dan minuman khas tersendiri,Ketika itu juga terpikir dalam untuk memiliki dan membelinya untuk sajian menu makan pagi hari dan sebaginya itu.walapun disaat membeli ada juga yang kurang segar akibat dengan layu akibat dari terjemur matahari dan tersimpan beberapa hari ini.dan disaat untuk makan kandungan vitaminnya pun berkurang.

Penelitian di Jerman baru-baru ini membuktikan hal-hal tersebut. Wortel-wortel yang memiliki rasa pahit rupanya mempunyai kandungan zat kimia bernama isocumarin atau 6-methoxymellein atau 3-methyl-6-methoxy-8-hydroxy-3,4-dihydro-isocumarin dalam konsentrasi tinggi. Zat ini diproduksi oleh wortel di kala stress.

Disaat kalau kita memesan menu makan di suatu tempat seperti halnya restroran ini baik untuk mulai memesan segelas wortel segar dengan dicampur oleh es dan dapat di minum dengan segar dimana jamuan makan berikutnya akan di hidangkan itu.disaat perut terasa kosong dan mulai meminum segela wortel akan lebih nikmat dan lebih baik untuk kesehatan dan kesegeran akan bola mata ini.

Selasa, 05 April 2011

Science Brain and Behavior contiuned 25

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send projections to the ventral thalamus and then to the premotor cortex.The basal ganglia
also receive widely and densely distributed projections from dopamine-producing
cells in the substantia nigra. Dopamine appears to be necessary for circuits in the basal
ganglia to function, and so it may indirectly participate in implicit-memory formation.
The connection from the cortex to the basal ganglia in the implicit-memory system
is unidirectional. Thus, most of the neocortex receives no direct information regarding
the activities of the basal ganglia, which Mishkin believes accounts for the
unconscious nature of implicit memories. In order for memories to be conscious, there
must be direct feedback to the neocortical regions involved. (Recall that, in the explicitmemory
system, the medial temporal regions send connections back to the neocortical
regions.)
Mishkin’s model shows why people with dysfunction of the basal ganglia, as occurs
in Parkinson’s disease, have deficits in implicit memory, whereas people with injuries to
the frontal or temporal lobes have relatively good implicit memories, even though they
may have profound disturbances of explicit memory. In fact, some people with
Alzheimer’s disease are able to play games expertly, even though they have no
recollection of having played them before.Daniel Schacter (1983) wrote of a golfer with
Alzheimer’s disease who retained his ability to play golf, despite some impairment of his
explicit knowledge of the events of having played a round, as indexed by his inability to
find shots or to remember his strokes on each hole. This man’s medial temporal system
was severely compromised by the disease, but his basal ganglia were unaffected.
HOW DO WE LEARN AND REMEMBER? ! 501
Korsakoff’s syndrome. Permanent loss
of the ability to learn new information
(anterograde amnesia) and to retrieve old
information (retrograde amnesia) caused
by diencephalic damage resulting from
chronic alcoholism or malnutrition that
produces a vitamin B1 deficiency.
(A) (B)
Prefrontal
cortex
Rest of
neocortex
Sensory and motor
information
Temporal-lobe
structures
Medial
thalamus
From brainstem to cortex systems
Acetylcholine
Serotonin
Noradrenaline
Prefrontal
cortex
Amygdala
Rhinal cortex Hippocampus
Neocortex
Thalamus
Basal
forebrain
Figure 13-14
Neural Circuit Proposed
for Explicit Memory
(A) General neuroanatomical
areas controlling explicit
memory. (B) Circuit diagram
showing the flow of
information, beginning with
inputs from the sensory and
motor systems, which are not
considered part of the
memory circuit.
Figure 13-15
Unidirectional Neural
Circuit Proposed
for Implicit Memory
(A) General anatomical areas
controlling implicit memory.
(B) Circuit diagram showing
the unidirectional flow of
information, beginning with
inputs from the sensory and
motor systems, which are
not considered part of the
memory circuit.
(A) (B)
Rest of
neocortex
Sensory
and motor
information
Basal
ganglia
Ventral
thalamus
Premotor
cortex
Substantia
nigra
Dopamine
Substantia
nigra
Amygdala
Basal Thalamus
ganglia
Premotor cortex
Review the locations of the basal
ganglia on the CD-ROM in the module
on the Central Nervous System
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502 ! CHAPTER 13
Korsakoff’s Syndrome
Focus on Disorders
Over the long term, alcoholism, especially when accompanied
by malnutrition, produces defects of memory. Joe R.
was a 62-year-old man who was hospitalized because his
family complained that his memory had become abysmal.
His intelligence was in the average range, and he had no obvious
sensory or motor difficulties. Nevertheless, he was unable
to say why he was in the hospital and usually stated that
he was actually in a hotel.
When asked what he had done the previous night, he
typically said that he “went to the Legion for a few beers with
the boys.” Although he had, in fact, been in the hospital, it
was a sensible response because that is what he had done
on most nights in the preceding 30 years. Joe R. was not certain
of what he had done for a living but believed that he had
been a butcher. In fact, he had been a truck driver for a local
delivery firm. His son was a butcher, however, and so, once
again, his story was related to something in his life.
Joe’s memory for immediate events was little better. On
one occasion, we asked him to remember having met us,
and then we left the room. On our return 2 or 3 minutes
later, he had no recollection of ever having met us or of having
taken psychological tests that we administered.
Joe R. had Korsakoff’s syndrome, a condition named after
Sergei Korsakoff, a Russian physician who in the 1880s first
called attention to a syndrome that accompanies chronic alcoholism.
The most obvious symptom is severe loss of memory,
including amnesia for both information learned in the
past (retrograde amnesia) and information learned since the
onset of the memory disturbance (anterograde amnesia).
One unique characteristic of the amnesic syndrome in Korsakoff
patients is that they tend to make up stories about past
events, rather than admit that they do not remember. Like
those of Joe R., however, these stories are generally plausible
because they are based on actual experiences.
Curiously, Korsakoff patients have little insight into their
memory disturbance and are generally indifferent to suggestions
that they have a memory problem. In fact, such patients
are generally apathetic to things going on around them. Joe
R. was often seen watching television when the set was not
turned on.
The cause of Korsakoff’s syndrome is a thiamine (vitamin
B1) deficiency resulting from prolonged intake of large
quantities of alcohol. Joe R. had a long history of drinking a
26-ounce bottle of rum every day, in addition to a “few beers
with the boys.” The thiamine deficiency results in the death
of cells in the midline diencephalon, including especially
the medial regions of the thalamus and the mammillary bodies
of the hypothalamus.
Most Korsakoff patients also show cortical atrophy,
especially in the frontal lobe. With the appearance of the
Korsakoff symptoms, which can happen quite suddenly,
prognosis is poor. Only about 20 percent of patients show
much recovery after a year on a vitamin B1–enriched diet.
Joe R. has shown no recovery after several years and will
spend the rest of his life in a hospital setting.
These PET scans, from a normal patient (larger image) and a
Korsakoff patient (inset), demonstrate reduced activity in the
frontal lobe of the diseased brain. (The frontal lobes are at the
bottom center of each scan.) Red and yellow represent areas of
high metabolic activity versus the lower level of activity in the
darker areas.
Courtesy Dr. Peter R. Martin from Alcohol Health & Research World,
Spring 1985, 9, cover.
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Neural Circuit for Emotional Memories
We now consider a third type of memory, emotional memory. Whether emotional
memories are implicit or explicit is not altogether clear; in fact, they seemingly could
be both. Certainly people can react with fear to specific stimuli that they can identify,
and we have seen that they can also fear situations for which they do not seem to have
specific memories.
Indeed, a common pathology is a panic disorder in which people show marked
anxiety but cannot identify a specific cause. For this reason, emotional memory can be
seen as a special form of memory. Emotional memory also has a unique anatomical
component—namely, the amygdala—discussed in detail in Chapter 11 and mentioned
earlier in the present chapter in regard to fear conditioning, in which the amygdala
seems to be responsible for our feelings of anxiety toward stimuli that by themselves
would not normally produce fear.
Emotional memory has been studied most thoroughly in fear conditioning by
pairing noxious stimuli, such as foot shock,with a tone (see Experiment 13-1).Michael
Davis (1992) and Joseph LeDoux (1995) used this type of experiment to demonstrate
that the amygdala is critical to emotional memory. Damage to the amygdala abolishes
emotional memory but has little effect on implicit or explicit memory.
The amygdala has close connections with the medial temporal cortical structures,
as well as with the rest of the cortex. It sends projections to structures controlling the
production of autonomic responses—namely, the hypothalamus and periaqueductal
gray matter (PAG) of the brainstem (Figure 13-16). In addition, the amygdala is connected
to the implicit-memory system through its connections with the basal ganglia.
The amygdala has connections to systems that control autonomic functions (e.g.,
blood pressure and heart rate) as well as connections to the hypothalamus and its control
of hormonal systems.
Fear is not the only type of emotional memory that is coded by the amygdala. A
study of severely demented patients by Bob Sainsbury and Marjorie Coristine (1986)
nicely illustrates this point. The patients were believed to have severe cortical abnormalities
but intact amygdalar functioning.
The researchers first established that the ability of these patients to recognize photographs
of close relatives was severely impaired. The patients were then shown four
photographs, one of which depicted a relative (either a sibling or a child) who had visited
in the past 2 weeks. The task was to identify the person whom they liked better
than the others. Although the subjects were unaware that they knew anyone in the
group of photographs, they consistently preferred the photographs of their relatives.
This result suggests that, although the explicit, and probably implicit, memory of the
HOW DO WE LEARN AND REMEMBER? ! 503
Retrograde amnesia. Inability to
remember events that took place before
the onset of amnesia.
Anterograde amnesia. Inability to
remember events subsequent to a
disturbance of the brain such as head
trauma, electroconvulsive shock, or
certain neurodegenerative diseases.
Emotional memory. Memory for the
affective properties of stimuli or events.
Hypothalamus
Amygdala
(A) (B) Frontal, parietal, temporal,
occipital, and cingulate cortices
Hypothalamus
and PAG
Striatum
Medial temporal
Amygdala cortex
Figure 13-16
Neural Circuit Proposed for
Emotional Memory (A) The key
structure in emotional memory is
the amygdala. (B) Circuit diagram
showing the flow of information
in emotional memory.
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relative was gone, each patient still had an emotional memory that guided his or her
preference.
Emotionally arousing experiences tend to be vividly remembered, a fact confirmed
by findings from both animal and human studies. James McGaugh (2004) concluded
that emotionally significant experiences, both pleasant and unpleasant, must activate
hormonal and brain systems that act to “stamp in” these vivid memories.
He noted that many neural systems likely take part, but the basolateral part of the
amygdala is critical. The general idea is that emotionally driven hormonal and chemical
systems (likely cholinergic and noradrenergic) stimulate the amygdala, which in
turn modulates the laying down of memory circuits in the rest of the brain, especially
in the medial temporal and prefrontal regions and basal ganglia. People with amygdala
damage would thus not be expected to have enhanced memory for emotion-laden
events, and they do not (Cahill et al., 1995).
STRUCTURAL BASIS OF BRAIN PLASTICITY
We have encountered three different categories of memory and the different brain circuits
that underlie each type.Our next task is to consider how the neurons in these circuits
change to store the memories. The consensus among neuroscientists is that the
changes take place at the synapse, in part because that is where neurons influence one
another.
This idea dates back to 1928,when Spanish anatomist Santiago Ramón y Cajal suggested
that the process of learning might produce prolonged morphological changes in
the efficiency of the synapses activated in the learning process. This idea turned out to
be easier to propose than to study. The major challenge that researchers still encounter
as they investigate Cajal’s suggestion is knowing where in the brain to look for synaptic
changes that might correlate with memory for a specific stimulus.
This task is formidable. Imagine trying to find the exact location of the neurons
responsible for storing your grandmother’s name. You would face a similar challenge
in trying to find the neurons responsible for the memory of an object in a monkey’s
brain as the monkey performs the visual-recognition task illustrated in Figure 13-11B.
Investigators have approached the problem of identifying synaptic change in two distinctly
different ways.
The first approach is to study simple neural systems. Recall from the experiments
in Chapter 5 that the study of Aplysia revealed that changes in the properties of the
synapse take place when animals learn the association between a noxious stimulus and
a cue signaling the onset of the stimulus. We saw as well that synaptic changes take
In Review .
Certain neural structures and circuits are associated with different types of learning and
memory. One system, consisting of the prefrontal cortex and the medial temporal lobe
and regions related to them, is the likely neural location of explicit memory. A second
system, consisting of the basal ganglia and neocortex, forms the neural basis for implicit
memory. A third system, which includes the amygdala and its associated structures, forms
the neural basis for emotional memory. Presumably, when we learn different types of information,
changes take place in synapses in these systems, and these changes produce
our memories of the experiences. We now turn to the question of what these synaptic
changes might be.
504 ! CHAPTER 13
Aplysia
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place in hippocampal slices in which long-term potentiation (LTP) is induced. The
identification of synaptic change is possible in Aplysia and in LTP because we know
where in the nervous system to look. But we have little information about where to
look for memory-storing synapses in mammals.
Accordingly, a second approach to finding the neural correlates of memory aims
to determine that synaptic changes are correlated with memory in the mammalian
brain. The next step is to localize the synaptic changes to specific neural pathways. Then
the task is to analyze the nature of the synaptic changes themselves.
The goal of this section is to describe the studies that have identified the presence
of synaptic changes correlated with various types of experience.We first consider the
general research strategy.We then look at the gross neural changes correlated with different
forms of experience, ranging from living in specific environments to learning
specific tasks or having specific experiences to the chronic administration of trophic
factors, hormones, and addictive drugs.We shall see that the general synaptic organization
of the brain is modified in a strikingly similar manner by each of these diverse
forms of experience.
Measuring Synaptic Change
In principle, experience could cause the brain to change in either of two ways: by modifying
existing circuitry or by creating novel circuitry. In actuality, the plastic brain uses
both strategies.
MODIFYING EXISTING CIRCUITS
The simplest way to find synaptic change is to look for gross changes in the morphology
of dendrites, which are essentially extensions of the neuron membrane that allow
more space for synapses. Because complex neurons, such as pyramidal cells, have 95
percent of their synapses on the dendrites, measurement of the changes in dendritic
extent can be used to infer synaptic change.
Cells that have few or no dendrites have limited space for inputs, whereas cells
that have complex dendritic structure may have space for tens of thousands of inputs.
More dendrites mean more connections, and fewer dendrites mean fewer connections.
Change in dendritic structure, therefore, implies change in synaptic
organization.
A striking feature of dendrites is that their shape is highly changeable. Dale
Purves and his colleagues (Purves & Voyvodic, 1987) labeled cells in the dorsal-root
ganglia of living mice with a special dye that allowed them to visualize the cells’ dendrites.
When they examined the same cells at intervals ranging from a few days to
weeks, they identified obvious qualitative changes in dendritic extent, as represented
in Figure 13-17.We can assume that new dendritic branches have new synapses and
that lost branches mean lost synapses.
An obvious lesson from the Purves studies is that the morphology of neurons is
not static. Instead, neurons change their structure in response to their changing experiences.
As they search for neural correlates of memory, researchers can take advantage
of this changeability by studying the changes in dendritic morphology that
are correlated with specific experiences, such as the learning of some task.
What do changes in dendritic morphology reveal? Let us consider the case in
which a given neuron generates more synaptic space. The new synapses that are
formed can be either additional synapses between neurons that were already connected
with the neuron in question or synapses between neurons that were not
formerly connected. Examples of these distinctly different synapse types are illus-
HOW DO WE LEARN AND REMEMBER? ! 505
Labeled
with dye
88–90
days later
Figure 13-17
Dendritic Plasticity Reconstructions of
parts of the dendrites of three mouse
superior cervical ganglion cells observed
at an interval of 3 months. Changes in both
the extension and the retraction of
particular dendritic branches are evident.
Adapted from “Imaging Mammalian Nerve Cells and
Their Connections over Time in Living Animals,” by
D. Purves and J. T. Voyvodic, 1987, Trends in
Neuroscience, 10, p. 400.
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trated in Figure 13-18 (see also “Dendritic Spines, Small but
Mighty” on page 181).
New synapses can result either from the growth of new
axon terminals or from the formation of synapses along
axons as they pass by dendrites. In both cases, however, the
formation of new synapses corresponds to changes in the
local circuitry of a region and not to the development of
new connections between distant parts of the brain. The
formation of new connections between widely separated
brain regions would be very difficult in a fully grown brain
because of the dense plexus of cells, fibers, and blood vessels
that lies in the way. Review “Optimizing Connections in the Brain” on
page 35.
Thus, the growth of new synapses indicates modifications to basic circuits
that are already in the brain. This strategy has an important implication
for the location of synaptic changes underlying memory. During development,
the brain forms circuits to process sensory information and to produce
behavior. These circuits are most likely to be modified to form memories, just as
in the Martin study discussed earlier (see Figure 13-6).
CREATING NOVEL CIRCUITS
Before the mid-1990s, the general assumption was that the mammalian brain did not
make new neurons in adulthood. The unexpected discovery in the 1970s that the brains
of songbirds such as canaries grow new neurons to produce songs in the mating season
led researchers to reconsider the possibility that the adult mammalian brain, too,
might be capable of generating new neurons. This possibility can be tested directly by
injecting animals with a compound that is taken up by cells when they divide to produce
new cells, including neurons.
When such a compound, bromode-oxyuridine (BrdU), is injected into adult rats,
dividing cells incorporate it into their DNA. In later analysis, a specific stain can be used
to identify the new neurons. Figure 13-19 shows such an analysis in the rat olfactory
bulb and hippocampus.
This technique has now yielded considerable evidence that the mammalian brain,
including the primate brain, can generate neurons destined for the olfactory bulb, hippocampal
formation, and possibly even the neocortex of the frontal and temporal lobes
(Eriksson et al., 1998; Gould et al., 1999). The reason is not yet clear, but adult neurogenesis
may enhance brain plasticity, particularly with respect to processes underlying
learning and memory. For example, Elizabeth Gould and her colleagues (1999) showed
that the generation of new neurons in the hippocampus is enhanced when animals learn
explicit-memory tasks such as the Morris water task (see Figure 13-3). Furthermore, as
we shall see, the generation of these new neurons appears to be increased by experience.
506 ! CHAPTER 13
Olfactory bulb Hippocampus
Figure 13-19
Neurogenesis in Adult
Rats Confocal microscopic
photographs: cells stained
red with an antibody
(called NeuN) to neurons
are neurons; cells stained
green with an antibody to
bromode-oxyuridine (BrdU)
are new cells including
both neurons and glia; cells
stained yellow are positive
for both red and green and
are new neurons.
Axon 1
Axon 2
Axon 3
Axon 1
New axon
New axon
New axon
collateral
Axon 2
Axon 3
(A) Before experience
(C) Various observed shapes of new dendritic spines
(B) After experience
Single synapse
on dendritic
spine
Formation of
new synapses
from new axon
terminals
Formation of
new synapses
from original
terminals
Figure 13-18
Effects of Experience (A) Three
inputs to a dendrite of a pyramidal cell.
Each axon forms a synapse with a
different dendritic spine. (B) Formation
of multiple spine heads. Either the
original axons may divide and innervate
two spine heads or new axons or
axon collaterals (dotted outlines)
may innervate the new spine heads.
(C) Single dendritic spines may sprout
multiple synapses.
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Enriched Experience and Plasticity
One way to stimulate the brain is to house animals in environments that provide some
form of generalized sensory or motor experience. Such an experiment is described in
Chapter 6: Donald Hebb took laboratory rats home and let them have the run of his
kitchen. After an interval, Hebb compared the “enriched” rats with another group of
rats that had remained in cages in his laboratory at McGill University, training both
groups to solve various mazes.
The enriched animals performed better, and Hebb concluded that one effect of the
enriched experience was to enhance later learning. This important conclusion laid the
foundation for the initiation of Head Start in the United States. This program provides
academic experiences for disadvantaged pre-school-aged children.
When subsequent investigators have worked with rats, they have opted for a more
constrained enrichment procedure that uses some type of “enriched enclosure.” For
example, in our own studies, we place groups of six rats in enclosures. These enclosures
give animals a rich social experience as well as extensive sensory and motor
experience.
The most obvious consequence of such experience is an increase in brain weight
that may be on the order of 10 percent relative to cage-reared animals, even though the
enriched rats typically weigh less, in part because they get more exercise. The key question
is, What is responsible for the increased brain weight? A comprehensive series
of studies by Anita Sirevaag and William Greenough (1988) used light- and electronmicroscopic
techniques to analyze 36 different aspects of cortical synaptic, cellular, and
vascular morphology in rats raised either in cages or in complex environments. The
simple conclusion was that there is a coordinated change not only in the extent of dendrites
but also in glial, vascular, and metabolic processes in response to differential experiences
(Figure 13-20).
Animals with enriched experience have not only more synapses per neuron but
also more astrocytic material, more blood capillaries, and higher mitochondrial volume.
(Higher mitochondrial volume means greater metabolic activity.) Therefore,
clearly, when the brain changes in response to experience, the expected neural changes
take place, but there are also adjustments in the metabolic requirements of the larger
neurons.
Gerd Kempermann and his colleagues (1998) sought to determine whether experience
actually alters the number of neurons in the brain. To test this idea, they compared
the generation of neurons in the hippocampi of mice housed in complex
environments with that of mice reared in laboratory cages. They located the number
of new neurons by injecting the animals with BrdU several times in the course of their
complex-housing experience.
HOW DO WE LEARN AND REMEMBER? ! 507
Enriched rat enclosure
Dendrite
length
Astrocyte
processes
Vascular
volume
Synapses/
neurons
0 10 20 30 40 50
Percent increase
Figure 13-20
Consequences of Enrichment Schematic summary of some cortical changes
that take place in response to experience. Note that such changes are found
not only in neurons but also in astrocytes and vasculature. Based on data from
“Differential Rearing Effects on Rat Visual Cortex Synapses. I. Synaptic and Neuronal Density
and Synapses per Neuron,” by A. Turner and W. T. Greenough, 1985, Brain Research, 329,
pp. 195–203; “Differential Rearing Effects on Rat Visual Cortex Synapses. III. Neuronal and Glial
Nuclei,” by A. M. Sirevaag and W. T. Greenough, 1987, Brain Research, 424, pp. 320–332; and
”Experience-Dependent Changes in Dendritic Arbor and Spine Density in Neocortex Vary with
Age and Sex,” by B. Kolb, R. Gibb, and G. Gorny, 2003, Neurobiology of Learning and Memory,
79, pp. 1–10.
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The BrdU was incorporated into new neurons that were generated in the brain
during the experiment. When they later looked at the hippocampi, they found more
new neurons in the complex-housed rats than in the cage-housed rats. Although the
investigators did not look in other parts of the brain, such as the olfactory bulb, similar
changes can reasonably be expected to have taken place in other structures. This result
is exciting because it implies that experience not only can alter existing circuitry
but also can influence the generation of new neurons and thus new circuitry.
Sensory or Motor Training and Plasticity
The studies showing neuronal change in animals housed in complex environments
demonstrate that large areas of the brain can be changed with such experience. This
finding leads us to ask whether specific experiences would produce synaptic changes in
localized cerebral regions.One way to approach this question is to give animals specific
experiences and then see how their brains have been changed by those experiences.Another
way is to look at the brains of people who have had a lifetime of some particular
experience.We will consider each of these research strategies separately.
MANIPULATING EXPERIENCE EXPERIMENTALLY
Perhaps the most convincing study of this sort was done by Fen-Lei Chang and William
Greenough (1982). They took advantage of the fact that the visual pathways of the laboratory
rat are about 90 percent crossed. That is, about 90 percent of the connections
from the left eye to the cortex project through the right lateral geniculate nucleus to
the right hemisphere, and vice versa for the right eye.
Chang and Greenough placed a patch over one eye of each rat and then trained the
animals in a maze. The visual cortex of only one eye would receive input about the
maze, but the auditory, olfactory, tactile, and motor regions of both hemispheres would
be equally active as the animals explored the maze. (Chang and Greenough also severed
the corpus callosum so that the two hemispheres could not communicate and
share information about the world.)
A comparison of the neurons in the two hemispheres revealed that those in the visual
cortex of the trained hemisphere had more extensive dendrites. The researchers
concluded that some feature associated with the encoding, processing, or storage of visual
input from training was responsible for the formation of new synapses, because
the hemispheres did not differ in other respects.
Complementary studies have been conducted by Randy Nudo and his colleagues
on the motor systems of monkeys. In the discussions of both the sensory and the motor
systems in Chapters 8 through 11, you learned that the sensory and motor worlds are
represented by cortical maps. For example, in the motor system are maps of the body
that represent discrete muscles and movements (see Experiment 10-4).
In the course of mapping the motor cortex of monkeys, Nudo and his colleagues
(1997) noted striking individual differences in their topography. The investigators
speculated that the individual variability might be due to each animal’s experiences up
to the time in life at which the cortical map was derived. To test this idea directly, they
trained two groups of squirrel monkeys to retrieve banana-flavored food pellets either
from a small or a large food well. A monkey was able to insert its entire hand into the
large well but only one or two fingers into the small well, as illustrated in the Procedures
section of Experiment 13-2.
Monkeys in the two groups were matched for number of finger flexions, which totaled
about 12,000 for the entire study. The monkeys trained on the small well improved
with practice,making fewer finger flexions per food retrieval as training proceded.Maps
of forelimb movements were produced by microelectrode stimulation of the cortex. The
508 ! CHAPTER 13
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maps showed systematic changes in the animals trained with the
small, but not the large, well. Presumably, these changes are due to the
more demanding motor requirements of the small-well condition.
The results of this experiment demonstrate that the functional topography
of the motor cortex is shaped by learning new motor skills,
not simply by repetitive motor use.
Most studies demonstrating plasticity in the motor cortex have
been performed on laboratory animals in which the cortex has been
mapped by microelectrode stimulation. Now the development of
new imaging techniques, such as transcranial magnetic stimulation
(TMS) and functional magnetic resonance imaging (fMRI),makes it
possible to show parallel results in humans who have special motor
skills. For example, there is an increased cortical representation of the
fingers of the left hand in musicians who play string instruments and
an increased cortical representation of the reading finger in Braille
readers. (We return to the details of these imaging techniques in
Chapter 14.)
Thus, the functional organization of the motor cortex is altered
by skilled use in humans. It can also be altered by chronic injury in
humans and laboratory animals (see Figure 10-26). Jon Kaas (2000)
showed that, when the sensory nerves from one limb are severed in
monkeys, large-scale changes in the somatosensory maps ensue. In
particular, in the absence of input, the relevant part of the cortex no
longer responds to stimulation of the limb, which is not surprising.
This cortex does not remain inactive, however. Rather, the deafferented
cortex begins to respond to input from other parts of the
body. The region that formerly responded to the stimulation of the
hand now responds to stimulation on the face, whose area is normally
adjacent to the hand area.
Similar results can be found in the cortical maps of people who
have had limbs amputated. For example, Vilayanur Ramachandran
(1993) found that,when the face of a limb amputee is brushed lightly
with a cotton swab, the person has a sensation of the amputated hand
being touched. Figure 13-21 illustrates the rough map of the hand
that Ramachandran was actually able to chart on the face. The likely
explanation is that the face area in the motor cortex has expanded to
occupy the deafferented limb cortex, but the brain circuitry still responds
to the activity of this cortex as representing input from the
limb. This response may explain the “phantom limb” pain often experienced
by amputees.
The idea that experience can alter cortical maps can be demonstrated
with other types of experience. For example, if animals are
trained to make certain digit movements over and over again, the
cortical representation of those digits expands at the expense of the
remaining motor areas. Similarly, if animals are trained extensively to
discriminate among different sensory stimuli such as tones, the auditory
cortical areas responding to those stimuli increase in size.
As indicated in the Focus on New Research at the beginning of
this chapter, one effect of musical training is to alter the motor representations
of the digits used to play different instruments, and we can speculate that
musical training is also likely to alter the auditory representations of specific sound frequencies.
Both changes are essentially forms of memory, and the underlying synaptic
changes are likely to take place on the appropriate sensory or motor cortical maps.
HOW DO WE LEARN AND REMEMBER? ! 509
Retrievals per day
0
1200
1000
800
600
400
200
0 2 4 6 8 10 12 14 16
Day of training Day of training
Retrievals per day
0
1200
1000
800
600
400
200
0 2 4 6 8 10 12 14 16
Difficult task
Procedures
Results
Simple task
EXPERIMENT 13-2
Question: Does the learning of a fine motor skill alter the cortical motor map?
The digit representation in the brain of the animal with the more
difficult task is larger, corresponding to the neuronal changes
necessary for the acquired skill.
Conclusion
One group of monkeys
was trained to retrieve
food from a small well.
Another group of monkeys
was trained to retrieve
food from a large well.
The motor representation of digit, wrist, and
arm was mapped.
Both groups were allowed 12,000 finger flexions. The smallwell
task was more difficult and required the learning of a fine
motor skill in order to match performance of the simpler task.
KEY
Digit Wrist/forearm Digit, wrist, and forearm
Adapted from “Adaptive Plasticity in Primate Motor
Cortex as a Consequence of Behavioral Experience and
Neuronal Injury,” by R. J. Nudo, E. J. Plautz, and G. W.
Milliken, 1997, Seminars in Neuroscience, 9, p. 20.
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EXPERIENCE-DEPENDENT CHANGE IN THE HUMAN BRAIN
According to the Ramachandran amputee study, the human brain appears to change
with altered experience. This study did not directly examine neuronal change, however;
neuronal change was inferred from behavior. The only way to directly examine synaptic
change is to look directly at brain tissue. Although the experimental manipulation
of experiences in people followed by an examination of their brains is not an option,
the brains of people who died from nonneurological causes can be examined and the
structure of their cortical neurons can be related to their experiences.
One way to test this idea is to look for a relation between neuronal structure and
education. Arnold Scheibel and his colleagues conducted many such studies in the
1990s (Jacobs & Scheibel, 1993; Jacobs, Scholl, & Scheibel, 1993). In one study, they
found a relation between the size of the dendrites in Wernicke’s area (a cortical language
area) and the amount of education. The cortical neurons from the brains of deceased
people with a college education had more dendritic branches than did those
from people with a high-school education, which, in turn, had more dendritic material
than did those from people with less education. People who have more dendrites
may be more likely to go to college, but that possibility is not easy to test.
Another way to look at the relation between human brain structure and behavior is
to correlate the functional abilities of people with their neuronal structure. For example,
one might expect to find differences in language-related areas between people with high
and low verbal abilities. This experiment is difficult to conduct, because it presupposes
behavioral measures taken before death and such measures are not normally available.
However, Scheibel and his colleagues took advantage of the now well-documented
observation that, on average, the verbal abilities of females are superior to those of
males. When they examined the structure of neurons in Wernicke’s area, they found
that females have more extensive dendritic branching there than males do. Furthermore,
in a subsequent study, they found that this sex difference was present as early as
age 9, suggesting that such sex differences emerge within the first decade. In fact, on
average, young girls tend to have significantly better verbal skills than young boys do.
Finally, these investigators approached the link between experience and neuronal
morphology in a slightly different way. They began with two hypotheses. First, they
suggested that there is a relation between the complexity of dendritic branching and
the nature of the computational tasks performed by a brain area.
To test this hypothesis, they examined the dendritic structure of neurons in different
cortical regions that handle different computational tasks. For example, when
they compared the structure of neurons corresponding to the somatosensory representation
of the trunk with those for the fingers, they found the latter to have morecomplex
cells. They reasoned that the somatosensory inputs from receptive fields on
the chest wall would constitute less of a computational challenge to cortical neurons
than would those from the fingers and that the neurons representing the chest would
therefore be less complex.
This hypothesis was shown to be correct (Figure 13-22). Similarly, when Scheibel’s
group compared the cells in the finger area with those in the supramarginal gyrus
(SMG), a region of the parietal lobe that is associated with higher cognitive processes
(that is, thinking), they found the SMG neurons to be more complex.
The group’s second hypothesis was that dendritic branching in all regions is subject
to experience-dependent change.As a result, the researchers hypothesized that predominant
life experience (e.g., occupation) should alter the structure of dendrites.Although
they did not test this hypothesis directly, they did make an interesting observation.
In their study comparing cells in the trunk area, the finger area, and the SMG, they
found curious individual differences. For example, especially large differences in trunk
and finger neurons were found in the brains of people who had a high level of finger dexterity
maintained over long periods of time (e.g., career word processors). In contrast,
510 ! CHAPTER 13
Ball
of thumb
Thumb
Pinkie finger
(A)
(B)
Cotton swab
Index finger
Figure 13-21
Cortical Reorganization When
the face of an amputee is stroked
lightly with a cotton swab (A), the
person experiences the touch as the
missing hand being lightly touched
(B) as well as experiencing touch to the
face. The deafferented cortex forms a
representation of the amputated hand
on the face. As in the normal map of
the somatosensory cortex, the thumb is
disproportionately large. Adapted from
“Behavioral and Magnetoencephalographic
Correlates of Plasticity in the Adult Human
Brain,” by V. S. Ramachandran, 1993, Proceedings
of the National Academy of Sciences, USA, 90,
p. 10418.
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no difference between trunk and finger neurons was found in a sales representative.One
would not expect a good deal of specialized finger use in this occupation, which would
mean less-complex demands on the finger neurons.
In summary, although the studies showing a relation between experience and neural
structure in humans are based on correlations rather than on actual experiments, the
findings are consistent with those observed in experimental studies of other species.We
are thus led to the general conclusion that specific experiences can produce localized
changes in the synaptic organization of the brain. Such changes likely form the structural
basis of memory.
Plasticity, Hormones, Trophic Factors, and Drugs
Articles in newspapers and popular magazines often report that drugs can damage
your brain. Some drugs certainly do act as toxins and can selectively kill brain regions,
but a more realistic mode of action of drugs is to change the brain. Although not many
studies have looked at drug-induced morphological changes, there is evidence that
some compounds can greatly change the synaptic organization of the brain. These
compounds include hormones, neurotrophic factors, and psychoactive drugs.We will
briefly consider each category.
HORMONES
As stated in earlier chapters, the levels of circulating hormones play a critical role both in
determining the structure of the brain and in eliciting certain behaviors in adulthood.Although
the structural effects of hormones were once believed to be expressed only in the
course of development, current belief is that adult neurons also can respond to hormonal
manipulations with dramatic structural changes.We will consider the actions of two types
of hormones detailed in Chapter 7, gonadal hormones and stress-related hormones.
We encountered the gonadal hormones in Chapters 6, 7, and 11. Research findings
have established that there are differences in the structure of neurons in the cortices of
male and female rats and that these differences depend on gonadal hormones.What is
more surprising, perhaps, is that gonadal hormones continue to influence cell structure
and behavior in adulthood.
Elizabeth Hampson and Doreen Kimura (1988) showed that the performance
of women on various cognitive tasks changes throughout the menstrual cycle as their estrogen
levels fluctuate.Changes in estrogen level appear to alter the structure of neurons
and astrocytes in the neocortex and hippocampus, which likely account for at least part
of the behavioral fluctuation. Figure 13-23 illustrates changes in the dendritic spines in
the hippocampal cells of female rats at different phases of their 4-day estrous cycle.As the
estrogen level rises, the number of synapses rises; as the estrogen level drops, the number
of synapses declines (Chapter 11).
Curiously, the influence of estrogen on cell structure may be different in the hippocampus
and neocortex. Jane Stewart found, for example, that,when the ovaries ofmiddle-
aged female rats are removed, estrogen levels drop sharply, producing an increase in
the number of spines on pyramidal cells throughout the neocortex but a decrease in spine
HOW DO WE LEARN AND REMEMBER? ! 511
Wernicke’s
area
Somatosensory
area
Finger
area
Trunk
area
Language
area
Figure 13-22
Experience and Neural Complexity
Confirmation of Scheibel’s hypothesis
that cell complexity is related to the
computational demands required of the
cell. Neurons that represent the trunk
area of the body have relatively less
computational demand than do cells
representing the finger region. In turn,
cells engaged in more-cognitive
functions (such as language, as in
Wernicke’s area) have greater
computational demand than do
those engaged in finger functions.
Figure 13-23
Hormones and Neuroplasticity Sections of dendrites from hippocampal cells during
times of high and low levels of estrogen during the rat’s 4-day estrous cycle reveal many
more dendritic spines during the period when estrogen levels are high. Adapted from
“Naturally Occurring Fluctuation in Dendritic Spine Density on Adult Hippocampal Pyramidal Neurons,”
by C. S. Woolley, E. Gould, M. Frankfurt, and B. S. McEwen, 1990, Journal of Neuroscience, 10, p. 4038.
Estrogen
levels high
Estrogen
levels low
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density in the hippocampus (Stewart & Kolb, 1994). How these synaptic changes might
influence processes such as memory is not immediately obvious, but the question is reasonable—
especially because menopausal women also experience sharp drops in estrogen
levels and a corresponding decline in verbal memory ability.
This question is also relevant to middle-aged men, who show a slow decline in
testosterone levels that is correlated with a drop in spatial ability. Rats that are gonadectomized
in adulthood show an increase in cortical spine density, much like the
ovariectomized females, although we do not know how this change is related to spatial
behavior. Nonetheless, a reasonable supposition is that testosterone levels might influence
spatial memory throughout life.
When the body is stressed, the pituitary gland produces adrenocorticotrophic
hormone (ACTH), which stimulates the adrenal cortex to produce steroid hormones
known as glucocorticoids (see Figure 7.20). Important in protein and carbohydrate metabolism,
controlling sugar levels in the blood and the absorption of sugar by cells,
glucocorticoids have many actions on the body, including the brain. Robert Sapolsky
(1992) proposed that glucocorticoids can sometimes be neurotoxic.
In particular, he found that, with prolonged stress, cells in the hippocampus appear
to be killed by glucocorticoids. Elizabeth Gould and her colleagues (1998) showed that
even brief periods of stress can reduce the number of new granule cells produced in the
hippocampus in monkeys,presumably through the actions of stress hormones.Evidence
of neuron death and reduced neuron generation in the hippocampus has obvious implications
for the behavior of animals, especially for processes such as spatial memory.
In sum, hormones can alter the synaptic organization of the brain and even the number
of neurons in the brain. Little is known today about the behavioral consequences of
such changes, but hormones can likely alter the course of plastic changes in the brain.
NEUROTROPHIC FACTORS
In the discussion on the origins of neurons in Chapter 6 you learned about neurotrophic
factors, chemical compounds that signal stem cells to develop into neurons or
glia. Neurotrophic compounds, listed in Table 13-2, also act to reorganize neural circuits.
The first neurotrophic factor was discovered in the peripheral nervous system
more than a generation ago; it is known as nerve growth factor (NGF). Nerve growth
factor is trophic (i.e., having to do with the process of nutrition) in the sense
that it stimulates neurons to grow dendrites and synapses, and, in some cases,
it promotes the survival of neurons.
Trophic factors are produced in the brain by neurons and glia. Trophic factors
can affect neurons both through cell-membrane receptors and by actually
entering the neuron to act internally on its operation. For example, trophic factors
may be released postsynaptically to act as signals that can influence the
presynaptic cell. Recall from Chapter 5 that the Hebb synapse, a synapse that
changes with use so that learning takes place, is hypothesized to employ just
such a mechanism.
Experience stimulates their production, and so neurotrophic factors have
been proposed as agents of synaptic change. For example, brain-derived neurotrophic
factor (BDNF) is increased when animals solve specific problems such
as mazes. This finding has led to speculation that the release of BDNF may enhance
plastic changes, such as the growth of dendrites and synapses.
Unfortunately, although many researchers would like to conclude that
BDNF has a role in learning, this conclusion does not necessarily follow. The behavior
of animals when they solve mazes differs from their behavior when they
remain in cages, and so we must first demonstrate that changes in BDNF, NGF,
or any other trophic factor are actually related to the formation of new synapses.
512 ! CHAPTER 13
Molecules Exhibiting
Neurotrophic Activities
Proteins initially characterized as neurotrophic
factors
Nerve growth factor (NGF)
Brain-derived neurotrophic factor (BDNF)
Neurotrophin 3 (NT-3)
Ciliary neurotrophic factor (CNTF)
Growth factors with neurotrophic activity
Fibroblast growth factor, acidic (aFGF or FGF-1)
Fibroblast growth factor, basic (bFGF or FGF-2)
Epidermal growth factor (EGF)
Insulin-like growth factor (ILGF)
Transforming growth factor (TGF)
Lymphokines (interleukin 1, 3, 6 or IL-1, IL-3, IL-6)
Protease nexin I, II
Cholinergic neuronal differentiation factor
Table 13-2
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Nevertheless, if we assume that trophic factors do act as agents of synaptic change, then
we should be able to use the presence of increased trophic factor activity during learning
as a marker of where to look for changed synapses associated with learning and memory.
PSYCHOACTIVE DRUGS
Many people commonly use stimulant drugs such as caffeine, and some use more psychoactively
stimulating drugs such as nicotine, amphetamine, or cocaine. The longterm
consequences of abusing psychoactive drugs are now well documented, but the
question of why these drugs cause problems remains to be answered. One explanation
for the behavioral changes associated with chronic psychoactive drug abuse is that the
brain is changed by the drugs.
One experimental demonstration of these changes is drug-induced behavioral
sensitization, often referred to simply as behavioral sensitization. Drug-induced behavioral
sensitization is the progressive increase in behavioral actions in response to repeated
administration of a drug, even when the amount given in each dose does not
change. Behavioral sensitization occurs with most psychoactive drugs, including amphetamine,
cocaine, morphine, and nicotine.
As the Results section in Experiment 5-3 shows,Aplysia becomes more sensitive to a
stimulus after repeated exposure to it. Psychoactive drugs appear to have a parallel action:
they lead to increased behavioral sensitivity to their actions. For example, a rat given
a small dose of amphetamine may show an increase in activity.When the rat is given the
same dose of amphetamine on subsequent occasions, the increase in activity is progressively
larger. If no drug is given for weeks or even months, and then the amphetamine is
given in the same dose as before, behavioral sensitization continues, which means that
some type of long-lasting change must have taken place in
the brain in response to the drug. Drug-induced behavioral
sensitization can therefore be viewed as a memory for
a particular drug.
The parallel between drug-induced behavioral sensitization
and other forms of memory leads us to ask if the
changes in the brain after behavioral sensitization are
similar to those found after other forms of learning. They
are. For example, there is evidence of increased numbers
of receptors at synapses and of more synapses in sensitized
animals.
In a series of studies, Terry Robinson and his colleagues
found a dramatic increase in dendritic growth and
spine density in rats that were sensitized to amphetamine,
cocaine, or nicotine relative to rats that received injections
of a saline solution (Robinson & Kolb, 2004). Experiment
13-3 compares the effects of amphetamine and saline
treatments on cells in the nucleus accumbens. Neurons
in the amphetamine-treated brains have more dendritic
branches and increased spine density. Repeated exposure
to psychoactive stimulant drugs thus alters the structure
of cells in the brain. These changes in turn may be related
to “learned addictions.”
These plastic changes were not found throughout the
brain. Rather, they were localized to such regions as the prefrontal cortex and nucleus
accumbens, both of which receive a large dopamine projection. Recall from Chapters
7 and 11 that dopamine is believed to play a significant role in the rewarding properties
of drugs (Wise, 2004). Other psychoactive drugs also appear to alter neuronal
HOW DO WE LEARN AND REMEMBER? ! 513
Nerve growth factor (NGF)
Neurotrophic factor that stimulates
neurons to grow dendrites and synapses
and, in some cases, promotes the survival
of neurons.
Drug-induced behavioral
sensitization. Escalating behavioral
response to the repeated administration of
a psychomotor stimulant such as
amphetamine, cocaine, or nicotine; also
called behavioral sensitization.
Amphetamine Saline
Rats that show sensitization
to amphetamine have
increased dendritic growth
and spine density…
…relative to salinetreated
rats that
served as controls.
Animals received multiple doses of
amphetamine. Neurons were drawn from
nucleus accumbens.
Nucleus
accumbens
The sensitization induced by repeated exposure to amphetamine
changes the structure of neurons in certain brain areas.
Conclusion
Question: What effect do repeated doses of amphetamine, a psychomotor stimulant, have
on neurons?
EXPERIMENT 13-3
Procedure
Results
Adapted from “Persistent Structural Adaptations in
Nucleus Accumbens and Prefrontal Cortex Neurons
Produced by Prior Experience with Amphetamine,”
by T. E. Robinson and B. Kolb, 1997, Journal of
Neuroscience, 17, p. 8495.
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structure: marijuana, morphine, and certain antidepressants change dendritic length
and spine density, although in somewhat different ways from those of stimulants. For
example, morphine produces a decrease in dendritic length and spine density in the
nucleus accumbens and prefrontal cortex (Robinson & Kolb, 2004).
What do changes in synaptic organization induced by drugs mean for later experience-
dependent plasticity? If rats are given amphetamine, cocaine, or nicotine for 2
weeks before being placed in complex environments, the expected increases in dendritic
length and spine density in the cortex do not happen (Kolb et al., 2003). This is not because
the brain can no longer change: giving the animals additional drug doses can still
produce change. Rather, something about prior drug exposure alters the way in which
the brain later responds to experience.Why prior drug exposure has this effect is now
yet known but, obviously, drug taking can have long-term effects on brain plasticity.
RECOVERY FROM BRAIN INJURY
The nervous system appears to be conservative in its use of mechanisms related to behavioral
change. This message is important: it implies that, if we wish to change the
brain, such as after injury or disease, then we should look for treatments that will produce
the types of neural changes that we have found to be related to learning, memory,
and other forms of behavioral change.
Partial recovery of function is common after brain injury, and the average person
would probably say that the process of recovery requires that the injured person relearn
lost skills, whether walking, talking, or using the fingers. But what exactly does recovery
entail? After all, a person with brain trauma or brain disease has lost neurons, and so the
brain may be missing critical structures that are needed for learning or memory.
Recall, for example, that H.M. has shown no recovery of his lost memory capacities,
even after 50 years of practice in trying to remember information. The requisite
neural structures are no longer there, and so relearning is simply not possible. In
H.M.’s case, the only solution would be to replace his lost medial temporal structures,
a procedure that at present is not feasible. But other people, such as Donna, whom we
meet next, do show some recovery.
Donna’s Experience with Brain Injury
Donna began dancing lessons when she was 4 years old, and she was a “natural.” By the
time she finished high school she had the training and skill necessary for a career with
a major dance company. Donna remembers vividly the day that she was chosen to play
In Review .
Experience produces plastic changes in the brain, including the growth of dendrites, the
formation of synapses, and the production of new neurons. Further, like environmental
stimulation, hormones, neurotrophic factors, and psychoactive drugs appear to be able to
produce long-lasting effects on brain morphology that are strikingly similar to those observed
when animals show evidence of memory for sensory events. These structural
changes include not only changes in synaptic organization, as inferred from the dendritic
analyses, but also changes in the numbers of neurons, at least in the hippocampus. Thus,
the neural changes that correlate with memory are similar to those observed in other situations
of behavioral change.
514 ! CHAPTER 13
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a leading role in The Nutcracker. She had marveled at the costumes as she
watched the popular Christmas ballet as a child, and now she would dance in
those costumes!
Although her career as a dancer was interrupted by the births of two children,
Donna never lost interest in dancing. In 1968, when both her children
were in school, she began dancing again with a local company. To her amazement,
she could still perform most of the movements, although she was rusty
on the classic dances that she had once memorized so meticulously. Nonetheless,
she quickly relearned. In retrospect, she should not have been so surprised,
because she had always had an excellent memory.
One evening in 1990, while on a bicycle ride, Donna was struck by a drunk
driver. Although she was wearing a helmet, she suffered a traumatic brain injury
that put her in a coma for several weeks.As she regained consciousness, she
was confused and had difficulty talking and understanding others. Her memory was
very poor, she had spatial disorientation and often got lost, she had various motor disturbances,
and she had difficulty recognizing anyone but her family and closest friends.
In the ensuing 10 months, Donna regained most of her motor abilities and language
skills, and her spatial abilities improved significantly.Nonetheless, she was shorttempered
and easily frustrated by the slowness of her recovery, symptoms that are
typical of people with brain trauma. She suffered periods of depression.
She also found herself prone to inexplicable surges of panic when doing simple
things. On one occasion early in her rehabilitation, she was shopping in a large supermarket
and became overwhelmed by the number of salad dressing choices. She ran
from the store, and only after she sat outside and calmed herself could she go back inside
to continue shopping.
Two years later, Donna was dancing once again, but she now found it very difficult
to learn new steps. Her emotions were still unstable, which was a strain on her family,
but her episodes of frustration and temper outbursts became much less frequent. A
year later, they were gone and her life was not obviously different from that of other
middle-aged women.
Some cognitive changes persisted, however. Donna seemed unable to remember
the names or faces of new people she met and was unable to concentrate if there were
distractions such as a television or radio playing in the background. She could not
dance as she had before her injury, although she did work at it diligently. Her balance
on sudden turns gave her the most difficulty. Rather than risk falling, she retired from
her life’s first love.
Donna’s experiences demonstrate the human brain’s capacity for continuously
changing its structure and ultimately its function throughout a lifetime. On the basis of
what we have learned in this chapter, we can identify three different ways in which
Donna could recover from her brain injury: she could learn new ways to solve problems,
she could reorganize the brain to do more with less, and she could generate new neurons
to produce new neural circuits.We will briefly examine these three possibilities.
Three-Legged Cat Solution
The simplest solution to recovery from brain injury is to compensate in a manner that
we call the “three-legged cat solution.” Cats that lose a leg to accident (and subsequent
veterinary treatment) quickly learn to compensate for the missing limb and once again
become mobile; they can be regarded as having shown recovery of function. The limb
is still gone, but the behavior has changed in compensation.
A similar explanation can account for many instances of apparent recovery of
function after brain injury. Imagine a right-handed person who has a stroke that leads
HOW DO WE LEARN AND REMEMBER? ! 515
The brain changes to correspond to the
new experiences and new abilities of these
dancers. When Donna returned to dancing
after a 10-year break, she retained much
of her skill, even though she had not
practiced at all. After her accident, Donna
had to relearn how to talk, walk, and
dance. She did not go through the same
learning process that she had experienced
as a child, but her brain had to change in
some way to allow her to regain her lost
abilities. That change had limits, however,
because she never recovered the ability
that these young women have—that is, to
learn new dances.
Digital Stock
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to the loss of the use of the right hand and arm. Unable to
write with the affected limb, she switches to her left hand.
This type of behavioral compensation is presumably associated
with some sort of change in the brain. After all,
if a person learns to use the opposite hand to write, some
changes in the nervous system must underlie this new
skill.
New-Circuit Solution
A second way to recover from brain damage is for the brain
to change its neural connections to overcome the neural
loss. This way is most easily accomplished by processes
that are similar to those that we considered for other forms
of plasticity. That is, the brain forms new connections that
allow it to “do more with less.”
Although this change in the brain would seem to be
logical, such changes appear to be fairly small. As a result,
there is relatively modest recovery in most instances
of brain injury, unless there is some form of intervention.
Stated differently, recovery from brain damage can be increased
significantly if the person engages in some form
of behavioral or pharmacological therapy. The therapy
must play a role in stimulating the brain to make new
connections and to do more with less.
Behavioral therapy, such as speech therapy or physiotherapy,
presumably increases brain activity, which
facilitates the neural changes. In a pharmacological intervention,
the patient takes a drug known to influence brain
plasticity. An example is nerve growth factor.When NGF
is given to animals with strokes that damaged the motor
cortex, there is an improvement in motor functions, such
as reaching with the forelimb to obtain food (Experiment
13-4).
The behavioral changes are correlated with a dramatic
increase in dendritic branching and spine density in
the remaining, intact motor regions. The morphological
changes are correlated with improved motor functions, such as
reaching with the forelimb to obtain food, as illustrated in Experiment
13-2 (Kolb et al., 1997). Recovery is by no means complete,
which is not surprising, because brain tissue is still missing.
In principle, we might expect that any drug that stimulates
the growth of new connections would help people recover from
brain injury. There is one important constraint, however. The
neural growth must be in regions of the brain that could influence
a particular lost function. For example, if a drug stimulated the
growth of synapses on cells in the visual cortex, we would not expect to find enhanced
recovery of hand use. The visual neurons play no direct role in moving the hand.
Rather, we would need a drug that stimulates the growth of synapses on neurons
that can control hand use, such as neurons in the premotor or prefrontal cortex.As mentioned
earlier, amphetamine has this action, and so we might predict that amphetamine
will stimulate motor recovery. This possibility is now undergoing clinical trials.
Bryan Kolb
Remaining
motor cortex
Stroke
Motor cortex
Nerve growth factor stimulates dendritic growth and increased spine
density in both normal and injured brains. These neuronal changes are
correlated with improved motor function after stroke.
Conclusion
Question: Does nerve growth factor stimulate recovery from stroke, influence neural structure,
or both?
EXPERIMENT 13-4
Procedure
Results
Control NGF
Lesion NGF + lesion
NGF increases dendrites
and spines.
Animals received a cortical stroke. Some were treated with
NGF; others were not. Skilled reaching was assessed.
Lesion reduces
dendrites and spines.
NGF after a stroke reverses
loss of dendrites and spines.
Adapted from “Nerve Growth Factor Treatment
Prevents Dendritic Atrophy and Promotes Recovery
of Function after Cortical Injury,” by B. Kolb, S. Cote,
A. Ribeiro-da-Silva, and A. C. Cuello, 1997,
Neuroscience, 76, p. 1146.
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Lost-Neuron-Replacement Solution
The idea that brain tissue could be transplanted from one animal to another goes back
to the beginning of the twentieth century. There is now good evidence that tissue from
fetal brains can be transplanted and will grow and form some connections in the new
brain. Unfortunately, in contrast with transplanted hearts or livers, transplanted brain
tissue functions poorly. The procedure seems most suited to conditions in which a
small number of functional cells are required, such as in the replacement of dopamineproducing
cells in Parkinson’s disease or in the replacement of superchiasmatic cells to
restore circadian rhythms.
In fact, by 2004, dopamine-producing cells had been surgically transplanted into
the striata of many Parkinson patients. Although the disease has not been reversed,
some patients, especially the younger ones, have shown functional gains that justify the
procedure. Nonetheless, the fact that the tissue is taken from aborted human fetuses
raises serious ethical issues that will not be easily resolved.
There is a second way to replace lost neurons. Because experience can induce the
brain to generate new neurons, we know that the brain is capable of making neurons
in adulthood. The challenge is to get the brain to do it after an injury.
The first breakthrough in this research was made by Brent Reynolds and Sam Weiss
(1992). Cells lining the ventricle of adult mice were removed and placed in a culture
medium. The researchers demonstrated that, if the correct trophic factors are added,
the cells begin to divide and can produce new neurons and glia. Furthermore, if the
trophic factors—particularly epidermal growth factor (EGF)—are infused into the
ventricle of a living animal, the subventricular zone generates cells that migrate into
the striatum and eventually differentiate into neurons and glia.
In principle, it ought to be possible to use trophic factors to stimulate the subventricular
zone to generate new cells in the injured brain. If these new cells were to migrate
to the site of injury and essentially to regenerate the lost area, then it might be
possible to restore at least some lost function. It seems unlikely that all lost behaviors
could be restored, however, because the new neurons would have to establish the same
connections with the rest of the brain that the lost neurons once had. This task would
be daunting, because the connections would have to be formed in an adult brain that
already had billions of connections. Nonetheless, there is at least reason to hope that
such a treatment might someday be feasible.
There may be another way to use trophic factors to stimulate neurogenesis and enhance
recovery.Recall that regions such as the hippocampus and olfactory bulb normally
produce new neurons in adulthood and that the number of neurons in these areas can be
influenced by experience. It is possible, therefore, that we could stimulate the generation
of new neurons in intact regions of the injured brains and that these neurons could help
the brain develop new circuits to restore partial functioning.Thus, experience and trophic
factors are likely to be used in studies of recovery from brain injury in the coming years.
In Review .
Learning to recover from brain injury poses a special problem, because the brain may lose
large areas of neurons and their associated functions. Three ways to compensate for the loss of
neurons are: learn new ways to solve problems, reorganize the brain to do more with less, and
replace the lost neurons. Although complete recovery is not currently practical, all three strategies
can be used to enhance recovery from injury. Moreover, rehabilitation programs will likely
begin to look at the possibility of combining these three ways to further enhance recovery. In
each case, however, recovery entails taking advantage of the brain’s capacity to change.
HOW DO WE LEARN AND REMEMBER? ! 517
Epidermal growth factor (EGF).
Neurotrophic factor that stimulates the
subventricular zone to generate cells that
migrate into the striatum and eventually
differentiate into neurons and glia.
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SUMMARY
How does the brain learn and remember? Two distinctly different forms of learning and
memory may be referred to as implicit and explicit. The neural circuits underlying them
are distinctly different: the reciprocal system for explicit (conscious) memory includes
medial temporal structures; the unidirectional system for implicit (unconscious) memory
includes the basal ganglia. Multiple subsystems within the explicit and implicit systems
control different aspects ofmemory. Emotional memory, a third form, has characteristics
of both implicit and explicit memory. The neural circuits for emotional memory are
unique in that they include the amygdala. Finally, episodic memory includes not only a
record of events (episodes) that occurred but also our presence there and our role in the
events. The frontal lobe likely plays a unique role in this autobiographical memory.
What changes take place in the brain in response to experience? The brain has the capacity
for structural change, which is presumed to underlie functional change. The
brain changes in two fundamental ways in response to experience. First, changes take
place in existing neural circuits. Second, novel neural circuits are formed, both by new
connections among existing neurons and by the generation of new neurons.
What stimulates plastic change in the brain? The key to brain plasticity is neural activity.
Through such activity, synapses are formed and changed. Neural activity can be
induced by general or specific experience, as well as by electrical or chemical stimulation
of the brain. Chemical stimulation may range from hormones to neurotrophic
compounds to psychoactive drugs.Much of the brain is capable of plastic change with
experience. Different experiences lead to changes in different neural systems.
How might brain plasticity stimulate recovery from injury? Plastic changes after brain
injury parallel those seen when the brain changes with experience. Changes related to
recovery do not always occur spontaneously, however, and must be stimulated either
by behavioral training or by the stimulating effects of psychoactive drugs or neurotrophic
factors. The key to stimulating recovery from brain injury is to produce an increase
in the plastic changes underlying the recovery.
KEY TERMS
REVIEW QUESTIONS
1. How does experience change the brain?
2. What are the critical differences between the studies of learning conducted by
Pavlov and those conducted by Thorndike?
amnesia, p. 488
anterograde amnesia, p. 503
conditioned response (CR),
p. 484
conditioned stimulus (CS),
p. 484
declarative memory, p. 489
drug-induced behavioral
sensitization, p. 513
emotional memory, p. 503
entorhinal cortex, p. 497
epidermal growth factor
(EGF), p. 517
episodic memory, p. 492
explicit memory, p. 488
eye-blink conditioning,
p. 484
fear conditioning, p. 484
implicit memory, p. 488
instrumental conditioning,
p. 486
Korsakoff ’s syndrome,
p. 501
learning set, p. 488
memory, p. 484
nerve growth factor (NGF),
p. 513
neuritic plaque, p. 498
parahippocampal cortex,
p. 497
Pavlovian conditioning,
p. 484
perirhinal cortex, p. 497
priming, p. 490
procedural memory, p. 489
retrograde amnesia, p. 503
unconditioned response
(UCR), p. 484
unconditioned stimulus
(UCS), p. 484
visuospatial learning,
p. 486
518 ! CHAPTER 13
neuroscience interact ive
Many resources are available for
expanding your learning on line:
www.worthpublishers.com/kolb/
chapter13
Try some self-tests to reinforce your
mastery of the material. Look at some
of the updates on current research.
You’ll also be able to link to other sites
that will reinforce what you’ve learned.
www.alz.org
Learn more about what happens when
memory function deteriorates in
Alzheimer’s disease.
On your CD-ROM, you can review the
brain anatomy that underlies learning
and memory in the module on the
Central Nervous System.
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3. Distinguish among explicit, implicit, and emotional memory:What are the
circuits for each?
4. What is the structural basis of neuroplasticity, and what are various methods for
studying its relation to behavior?
5. Why are there changes in sensory representations after amputation of a limb?
6. What mechanisms might account for recovery from brain injury?
FOR FURTHER THOUGHT
1. Imagine that a person has a stroke and loses a large part of the left hemisphere,
rendering him unable to speak. Imagine further that a treatment has been
devised in which new neurons can be generated to replace the lost brain regions.
What would be the behavioral consequences of this brain regeneration? Would
the person be the same as he was before the stroke? (Hint: The new cells would
have no experiences.)
2. How do we learn from experience?
3. Our life is filled with experiences that alter brain organization. How might
different experiences interact with one another?
RECOMMENDED READING
Florence, S. L., Jain, N., & Kaas, J. H. (1997). Plasticity of somatosensory cortex in primates.
Seminars in Neuroscience, 9, 3–12. Jon Kaas and his colleagues are leaders in the study
of brain plasticity. This very readable review introduces the reader to the exciting
discoveries that Kaas and his colleagues are making in the study of cortical plasticity in
monkeys.
Fuster, J. M. (1995).Memory in the cerebral cortex. Cambridge, MA: MIT Press. Joaquin
Fuster has summarized the evidence on how the cortex codes information for storage
and retrieval, and he presents a cogent theory of how the cortex allows us to learn and
to remember.
Gazzaniga, M. S. (Ed.). (2000). The new cognitive neurosciences. Cambridge, MA: MIT Press.
This edited book spans the entire field of cognitive neuroscience. There is something
for everyone in this broad and well-written collection of chapters.
Hebb, D. O. (1949). The organization of behavior. New York:Wiley. Although this book was
written 50 years ago, it remains the clearest introduction to the fundamental questions
about how the brain can learn.
Kolb, B., & Whishaw, I. Q. (1998). Brain plasticity and behavior. Annual Review of Psychology,
49, 43–64. The authors provide a general review of the field of brain plasticity and
behavior. Any student writing a paper on this topic would do well to start with this
article and its extensive bibliography.
Sapolsky, R. M. (1992). Stress, the aging brain, and the mechanisms of neuron death.
Cambridge, MA: MIT Press. Robert Sapolsky is a leading researcher and theorist
interested in the role of hormones and brain function. This very readable text not only
introduces the reader to the basic facts but also provides a provocative broth of ideas.
Squire, L. (1987).Memory and brain. New York: Oxford University Press. Larry Squire is
perhaps the most visible cognitive neuroscientist studying brain mechanisms
underlying memory. This monograph is the best single volume describing what is
known about the organization of the brain and memory.
Wise, R. A. (2004). Dopamine, learning and motivation. Nature Neuroscience Reviews, 5,
483–494. A provocative review that leads to the conclusion that dopamine is necessary
not only for reward but even for learning.
HOW DO WE LEARN AND REMEMBER? ! 519
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Focus on Comparative Biology: Animal Intelligence
The Nature of Thought
Characteristics of Human Thought
The Neural Unit of Thought
Cognition and the Association Cortex
Knowledge about Objects
Spatial Cognition
Attention
Focus on New Research: Pay Attention!
Planning
Imitation and Understanding
Studying the Human Brain
and Cognition
Methods of Cognitive Neuroscience
Focus on Disorders: Neuropsychological Assessment
The Power of Cognitive Neuroscientific Analysis
Cerebral Asymmetry in Thinking
Anatomical Asymmetry
Functional Asymmetry in Neurological Patients
Functional Asymmetry in the Normal Brain
The Split Brain
Explaining Cerebral Asymmetry
The Left Hemisphere, Language, and Thought
Variations in Cognitive Organization
Sex Differences in Cognitive Organization
Handedness and Cognitive Organization
Focus on Disorders: The Sodium Amobarbital Test
Synesthesia
Focus on Disorders: A Case of Synesthesia
Intelligence
The Concept of General Intelligence
Multiple Intelligences
Divergent and Convergent Intelligence
Intelligence, Heredity, Environment, and the Synapse
Consciousness
Why Are We Conscious?
What Is the Neural Basis of Consciousness?
520 !
C H A P T E R 14
How Does the Brain Think?
Left: Carolina Biological Supply/Phototake. Middle: Paul Chesley/Tony Stone.
Right: Scott Camazine & Sue Trainor/Photo Researchers.
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He can also label various items made of metal (chain, key,
grate, tray, toy truck), wood (clothespin, block), and plastic
or paper (cup, box). Most surprising of all, he can use words
to identify, request, and refuse items and to respond to
questions about abstract ideas, such as the color, shape,
material, relative size, and quantity of more than 100 different
objects.
Alex’s thinking is often quite complex. Suppose he is
presented with a tray that contains the following seven
items: a circular rose-colored piece of rawhide, a piece of
purple wool, a three-corner purple key, a four-corner yellow
piece of rawhide, a five-corner orange piece of rawhide,
a six-corner purple piece of rawhide, and a purple
metal box. If he is then asked, “What shape is the purple
hide?” he will answer correctly, “Six-corner.” To come up
with this answer, Alex must comprehend the question, locate
the correct object of the correct color, determine the
answer to the question about that object’s shape, and encode
his answer into an appropriate verbal response.
This task is not easy to do. After all, there are four
pieces of rawhide and three purple objects, so Alex cannot
respond to just one attribute. He has to mentally combine
the concepts of rawhide and purple and find the object that
possesses them both. Then he has to figure out the object’s
shape. Clearly, considerable mental processing is required,
but Alex succeeds at such tasks time and
again.
Alex also demonstrates that he understands what
he is saying. If he requests one object and is presented
with another, he is likely to say no and repeat his original
request. In fact, when given incorrect objects on
numerous occasions in formal testing, he said no and
repeated his request 72 percent of the time, said no
without repeating his request 18 percent of the time,
and made a new request the other 10 percent of the
time. Such responses suggest that Alex’s requests lead
to an expectation in his mind. He knows what he is
asking for, and he expects to get it.
Alex’s cognitive abilities are unexpected in a
bird. We all know that parrots can talk, but most of
us assume that there is no real thought behind their words.
Alex proves otherwise. In the past 30 years, there has been
Animal Intelligence
Focus on Comparative Biology
A fundamental characteristic of intelligent animals is
that they think. We begin to explore how the brain
thinks and where thinking takes place in the brain by examining
thought in an intelligent nonhuman animal—
an African gray parrot named Alex, pictured here with
Irene Pepperberg (1990, 1999), who has been studying
Alex’s ability to think and use language for nearly three
decades.
A typical session with Alex and Pepperberg might proceed
as follows (Mukerjee, 1996): Pepperberg shows Alex
a tray with four corks. “How many?” she asks. “Four,” Alex
replies. She then shows him a metal key and a green plastic
one.
“What toy?”
“Key.”
“How many?”
“Two.”
“What’s different?”
“Color.”
Alex does not just have a vocabulary; the words have
meaning to him. He can correctly apply English labels to
numerous colors (red, green, blue, yellow, gray, purple,
orange), shapes (two-, three-, four-, five-, six-corner), and
materials (cork, wood, rawhide, rock, paper, chalk, wool).
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Alex, an African gray parrot, and Irene Pepperberg, along with
items of various shapes and colors, which Alex can count,
describe, and answer questions about.
Wm. Munoz
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ing must be an activity of complex neural circuits and not
of some particular region in the brain.
great interest in the intellectual capacities of chimpanzees
and dolphins, but Alex’s mental life appears to be just as
rich as those two large-brained mammals.The fact that birds
such as Alex are capable of forms of “thought” is a clue to
the neural basis of thinking. At first, a logical presumption
may be that thinking, which humans are so good at, must
be due to some special property of the massive human neocortex.
But birds do not possess a neocortex. Rather, birds
evolved specific brain nuclei that function much as the layers
of the cortex do. This difference in organization of the
forebrain between birds and mammals implies that think-
522 ! CHAPTER 14
The idea of neural circuits is the essence of Donald Hebb’s concept that cell
assemblies (networks of neurons) represent objects or ideas, and the interplay
among those networks results in complex mental activity. As you have seen in
the last few chapters, connections among neurons are not random but rather are organized
into systems (e.g., the visual, auditory, and motor systems) and subsystems
(such as the dorsal and ventral streams of vision). Thinking, therefore, must be due
to the activity of many different systems, which in the mammalian brain are in the
cortex.
This chapter examines the organization of the neural systems and subsystems that
control thinking. Our first task is to define the mental processes that we wish to study.
In other words,What is the nature of thought? We then consider the cortical regions
that play the major roles in thinking. You have encountered all these regions before in
the course of studying vision, audition, and movement. Here we examine how these
same regions may function to produce thought.
One characteristic of how the cortex is organized to produce thought is that fundamentally
different types of thinking are carried out in the left and right cerebral
hemispheres. As a result, this chapter also explores the asymmetrical organization of
the brain. Another distinguishing feature of human thought is that there are individual
differences in the ways that people think.We consider several sources of these differences,
including those related to sex and to what we call intelligence. Finally, we
address consciousness and how it may relate to the neural control of thought.
THE NATURE OF THOUGHT
The study of thought, language, memory, emotion, and motivation is tricky because
these mental processes are abstract. They cannot be seen. They can be inferred from
behavior and are best thought of as psychological constructs, ideas that result from a
set of impressions. The mind constructs the idea as being real, even though it is not a Cell assembly. Hypothetical group of
neurons that become functionally
connected because they receive the same
sensory inputs. Hebb proposed that cell
assemblies were the basis of perception,
memory, and thought.
Psychological construct. Idea,
resulting from a set of impressions, that
some mental ability exists as an entity;
examples include memory, language, and
emotion.
Human
Cerebrum Cerebellum Cerebrum Cerebellum
Parrot
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tangible thing. Thought is a psychological construct built from the impression that
people are constantly monitoring events and behaviors in their minds.
We have the impression that people are good or bad at forming these things that
we call thoughts, even though thoughts do not really exist as things.We run into trouble,
however, when we try to locate constructs such as thought or memory in the brain.
The fact that we have English words for these constructs does not mean that the brain
is organized around them. Indeed, it is not.
For instance, although people talk about memory as a unitary thing, the brain does
not treat memory as something unitary that is localized in one particular place (Chapter
13). In fact, there are many forms of memory, each of which is treated differently
by quite widely distributed brain circuits. Thus, this psychological construct of memory
that we think of as being a single thing turns out not to be unitary at all.
Even though making assumptions about psychological constructs such as memory
and thought is risky, we should certainly not give up searching for how the brain produces
them. The assumption of a neurological basis for psychological constructs has
perils, but it does not mean that we should fail to consider brain locations for these
constructs. After all, thought, memory, emotion, motivation, and other constructs are
the most interesting activities performed by the brain.
Psychologists typically use the term cognition to describe the processes of thought.
The term cognition means “knowing.” It refers to the processes by which we come to
know about the world.
For behavioral neuroscientists, cognition usually entails the ability to pay attention
to stimuli, whether external or internal, to identify these stimuli, and to plan
meaningful responses to them. External stimuli are those that stimulate neural activity
in our sensory receptors. Internal stimuli include cues from the autonomic nervous
system as well as from neural processes related to constructs such as memory and
motivation.
Characteristics of Human Thought
Although human cognition is widely believed to have unique characteristics, in what
ways, exactly, is it unique? Many may answer that human thought is verbal,whereas the
thought of other animals is nonverbal. Language is presumed to give humans an edge
in thinking, and in some ways it does:
Language provides the brain with a way to categorize information, allowing us to
easily group together objects, actions, and events that have factors in common.
Language provides a means of organizing time, especially future time. It enables us
to plan our behavior around time (such as “Monday at 3:00 PM”) in ways that nonverbal
animals cannot.
Perhaps most important, human language has syntax—sets of rules about how
words are put together to create meaningful utterances (Chapter 9).
Linguists argue that, although other animals, such as chimpanzees, can use and
recognize a large number of sounds (about three dozen for chimps), they do not
arrange these sounds in different orders to produce new meanings. Because of this lack
of syntax, chimpanzee language is literal and inflexible (but see “The Origins of Spoken
Language” on page 11). Human language, in contrast, has enormous flexibility, which
enables us to talk about virtually any topic, even highly abstract ones. In this way, our
thinking is carried beyond a rigid here and now.
HOW DOES THE BRAIN THINK? ! 523
Cognition. Act or process of knowing or
coming to know; in psychology, used to
refer to the processes of thought.
Syntax. Ways in which words are put
together to form phrases, clauses, or
sentences; proposed to be a unique
characteristic of human language.
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The importance of syntax to human thinking is illustrated by Oliver Sacks’s description
of Joseph, an 11-year-old deaf boy who was raised without sign language for
his first 10 years, and so was never exposed to syntax. According to Sacks:
Joseph saw, distinguished, used; he had no problems with perceptual categorization
or generalization, but he could not, it seemed, go much beyond this,
hold abstract ideas in mind, reflect, play, plan.He seemed completely literal—
unable to juggle images or hypotheses or possibilities, unable to enter an
imaginative or figurative realm. . . . He seemed, like an animal, or an infant,
to be stuck in the present, to be confined to literal and immediate perception.
. . . (Sacks, 1989, p. 40)
As stated in Chapter 9, language, including syntax, develops innately in children
because the brain is programmed to use words in a form of universal grammar. However,
in the absence of words—either spoken or signed—there can be no development
of grammar. And, without the flexibility of language that grammar allows, there can
also be no “higher level” thought.
Without syntactical language, thought is stuck in the world of concrete, here-andnow
perceptions. Syntactical language, in other words, influences the very nature of
our thinking.We will return to this idea when we consider the differences between the
thought processes of the left and right hemispheres.
In addition to arranging words in syntactical patterns, the human brain appears to
have a passion for stringing together events, movements, and thoughts. For example,
we combine notes into melodies,movements into dances, and images into movies.We
design elaborate rules for games and governments. To conclude that the human brain
is organized to structure events, movements, and thoughts into chains seems reasonable.
Syntax is merely one example of this innate human way of thinking about the
world.
We do not know how this propensity to string things together evolved, but one
possibility is that there is natural selection for stringing movements together. Stringing
movements together into sequences can be highly adaptive. For instance, it would allow
for building houses or weaving fibers into cloth.
William Calvin (1996) proposed that the most important motor sequences to ancient
humans were those used in hunting. Throwing a rock or a spear at a moving target
is a complex act that requires much planning. Sudden ballistic movements, such as
throwing, last less than an eighth of a second and cannot be corrected by feedback. The
brain has to plan every detail of these movements and then spit them out as a smoothflowing
sequence.
A modern-day football quarterback does so when he throws a football to a receiver
who is running a zigzag pattern to elude a defender. A skilled quarterback can hit the
target on virtually every throw, stringing his movements together rapidly in a continuous
sequence with no pauses or gaps. This skill is unique to humans. Although chimpanzees
can throw objects, their throws are not accurate. No chimpanzee could learn
to throw a ball to hit a moving target.
The human predisposition to sequence movements may have encouraged our development
of language. Spoken language, after all, is a sequence of movements of the
tongue and mouth. Viewed in this way, the development of language is a by-product
of a brain that was already predisposed to operate by stringing movements, events, or
even ideas together.
A critical characteristic of human motor sequencing is that we are able to create
novel sequences with ease.We constantly produce new sentences, and composers and
choreographers earn a living creating new sequences in music and dance. Creating
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novel sequences of movements or thoughts is a function of the frontal lobes. People
with damaged frontal lobes have difficulty generating novel solutions to problems, and
they are described as lacking imagination. As you know, the frontal lobes are critical to
the organization of behavior; it turns out that they are critical to the organization of
thinking as well.One of the major differences between the human brain and the brains
of other primates is the size of the frontal lobes.
The Neural Unit of Thought
What exactly goes on within the brain to produce what we call thinking? In the discussion
of Alex the parrot, we concluded that thinking must result from the activity of
complex neural circuits rather than being the property of some particular region in the
brain. One way to identify the role of neural circuits is to consider the responses of individual
neurons during cognitive activity.
William Newsome and his colleagues (1995) took this approach in training monkeys
to identify the presence of apparent motion in a set of moving dots on a television
screen. Experiment 14-1 shows their procedure. The researchers varied the difficulty of
the task by manipulating the number of dots that moved in the same direction. For instance,
if all the dots are made to move in the same direction, perceiving the whole array
of dots as moving in that direction is very easy. If only a small percentage of the dots are
HOW DOES THE BRAIN THINK? ! 525
Random dot movement
(no apparent motion
perceived)
Semirandom dot movement
(still no apparent
motion perceived)
Semicoordinated dot
movement (threshold level
needed to perceive
apparent motion)
Coordinated dot movement
(apparent motion
strongly perceived)
Monkeys were trained to identify
apparent motion in a set of
moving dots on a TV screen.
After the monkeys were trained in the task, investigators recorded from single neurons
in visual area V5, which contains cells that are sensitive to motion in a preferred
direction. The neural responses to the four different patterns of movement shown above
The increase in firing rate correlates with the monkey’s perception of motion, suggesting that
perception is influenced by individual neurons, not by the summed activity of many neurons.
Conclusion
Question: How do individual neurons mediate cognitive activity?
EXPERIMENT 14-1
Procedure
Results
Baseline response Baseline response Moderate response Strong response
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made to move in the same direction, however, perceiving apparent motion in that direction
is much more difficult.
In fact, a threshold number of dots moving together is required to create apparent
motion. If the number of dots moving in the same direction is too small, the viewer
gets an impression of random movement. Apparently, on the basis of the proportion
of dots moving in the same direction, the brain decides whether dots are moving in a
consistent direction.
After the monkeys had been trained in the task, the investigators recorded from
single neurons in visual area V5, which contains cells that are sensitive to movement in
a preferred direction. Consider a neuron that is sensitive to motion in the vertical direction.
Such a neuron responds with a vigorous burst of action potentials when there
is vertical movement in its receptive field. But, just as the observer has a threshold for
the perception of coherent motion in one direction, so, too, does the neuron. In other
words, if at some point random activity of the dots increases to a level at which it obscures
movement in a neuron’s preferred direction, that neuron will stop responding
because it does not detect any consistent pattern.
So the question becomes: How does the activity of any given neuron correlate with
the perceptual threshold for apparent motion? On the one hand, if our perception of
apparent motion results from the summed activity of many dozens, or even thousands,
of neurons, there should be little correlation between the activity of any one neuron
and that perception. On the other hand, if our perception of apparent motion is influenced
by individual neurons, then there should be a strong correlation between the
activity of a single cell and that perception.
The results of the experiment were unequivocal: the sensitivity of individual neurons
was very similar to the perceptual sensitivity of the monkeys to apparent motion.
In other words, if individual neurons failed to respond to the stimulus, the monkeys
behaved as if they did not perceive any apparent motion. This finding is curious. Given
the large number of V5 neurons, one would think that perceptual decisions are based
on the responses of a large pool of neurons. But Newsome’s results show that the activity
of individual cortical neurons is correlated with perception.
Still, there must be some way of converging the inputs of individual neurons to arrive
at a consensus. This convergence of inputs can be explained by Hebb’s idea of a
cell assembly—an ensemble of neurons that represents a complex concept. In this case,
the ensemble of neurons represents a sensory event (apparent motion), which the activity
of the ensemble detects.
Such cell assemblies could be distributed over fairly large regions of the brain or
they could be confined to smaller areas, such as cortical columns. Cognitive scientists
have developed computer models of these circuits and have demonstrated that they are
capable of sophisticated statistical computations with reasonably high efficiency. The
performance of other complex tasks, such as Alex the parrot’s detection of an object’s
color, also are believed to entail ensembles of neurons. These cell assemblies provide
the basis for cognition. Different ensembles combine together,much like words in language,
to produce coherent thoughts.
What is the contribution of individual neurons to a cell assembly? Each neuron acts
as a computational unit. As Experiment 14-1 shows, even one solitary neuron is capable
of deciding on its own when to fire if its summed inputs indicate that movement is
taking place. Neurons are the only elements in the brain that combine evidence and
make decisions. They are the foundation of thought and cognitive processes.
The combination of these individual neurons into novel neural networks produces
complex mental representations, such as ideas. Our next step is to determine where
the cell assemblies for various complex cognitive processes are located in the human
brain.
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COGNITION AND THE ASSOCIATION CORTEX
In Chapters 8 through 11, we considered the regions of the cortex responsible for deciphering
inputs from sensory receptors and for executing movements. These regions
together occupy about a third of the cortex (Figure 14-1). The remaining cortex,
located in the frontal, temporal, and parietal lobes, is often referred to
as the association cortex, which functions to produce cognition.
A fundamental difference between the association cortex and the
primary sensory and motor cortex is that the association cortex has a
distinctive pattern of connections. Recall that a major source of input
to all cortical areas is the thalamus. The primary sensory cortex receives
inputs from thalamic areas that receive information from the
sense organs. In contrast, the association cortex receives its inputs
from regions of the thalamus that receive their inputs from other regions
of the cortex.
As a result, the inputs to the association cortex have been highly
processed before they get to the association regions. This information must therefore
be fundamentally different from the information reaching the primary sensory and
motor cortex. The association regions contain knowledge, either about our external or
internal world or about movements. To understand the types of knowledge that the association
areas contain, we consider different forms of cognitive behavior and then
trace these behaviors to different parts of the association cortex.
Knowledge about Objects
Imagine looking at a cardboard milk carton sitting on a counter directly in front of you.
What do you see? Now, imagine moving the carton off to one side. What do you see
now? Next, tilt the carton toward you at a 45° angle. Again, what do you see? Probably
you answered that you saw the same thing in each situation: a white rectangular object
with colored lettering on it.
Intuitively, you probably feel that the brain must “see” the object much as you have
perceived it. As you learned in Chapter 8, however, the brain’s “seeing” is more compartmentalized
than are your perceptions. This compartmentalizaton is revealed in
people who suffer damage to different regions of the occipital cortex. They often lose
one particular aspect of visual perception. For instance, those with damage to visual
area V4 can no longer perceive color, whereas those with damage to area V5 can no
longer see movement (when the milk carton moves, it becomes invisible to them).
Moreover, your perception of the milk carton’s rectangular shape is not always a
completely accurate interpretation of the forms that your visual system is processing.
In Review .
Thought is the act of attending to, identifying, and making meaningful responses to stimuli.
Many animals, probably including all mammals and birds, are capable of thought. Unlike
thought in other animals, human thought has the added flexibility of language, which
influences the nature of human thinking. Human thought is also characterized by the ability
to generate strings of ideas, many of which are novel. The basic unit of thought is the
neuron. The cell assembly is the vehicle by which neurons interact to influence behavior
and to produce cognitive processes.
HOW DOES THE BRAIN THINK? ! 527
Association cortex. Neocortex outside
the primary sensory and motor cortices
that functions to produce cognition.
KEY (cortical areas)
Primary motor
Primary sensory
Primary visual
Primary auditory
Primary olfactory
and taste
Primary olfactory
and taste cortex (hidden
by temporal lobe)
All cortex that is not primary
cortex is association cortex.
Figure 14-1
Cortical Functions Lateral and medial
views of the left and right hemisphere,
respectively, showing the primary motor
and sensory areas. All remaining cortical
areas are collectively referred to as
association cortex, which functions in
thinking.
Review the locations of these brain
regions on the CD in the module on the
Central Nervous System.
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When the carton is tipped toward you, you still perceive it as rectangular, even though
it is no longer presenting a rectangular shape to your eyes. Your brain has somehow ignored
the change in information about shape that your retinas have sent it and concluded
that this shape is still the same milk carton.
This example demonstrates many properties of visual perception. But there is
more to your conception of the milk carton than merely processing its physical characteristics.
For example, you know what a milk carton is, what it contains, and where
you can get one. This knowledge about milk cartons that you have acquired is represented
in the temporal association cortex that forms the ventral stream of visual
processing. If the temporal association regions are destroyed, a person loses visual
knowledge not only about milk cartons but also about all other objects. Like D. F.,
whose case is discussed in Chapter 8, the person becomes agnosic.
Knowledge about objects includes even more than simply knowing what they are
and what they are used for. Two cases described by Martha Farah (1995) illustrate
this point. Case 1 was unable to localize visual stimuli in space and to describe the
location of familiar objects from memory. He was, however, good at both identifying
objects and describing their appearance from memory. In other words, Case 1
could both perceive and imagine objects, but he could not perceive or imagine their
location.
Case 2 was the opposite of Case 1. Case 2 could localize objects and describe their
locations from memory, but he could not identify objects or describe them from
memory. Case 1 had a lesion in the parietal association cortex, whereas Case 2’s lesion
was in the temporal association cortex. Knowledge about objects is thus found in
more than one location, depending on the nature of the knowledge. Knowledge of
what things are is temporal; knowledge of where things are is parietal.
Spatial Cognition
The location of objects is just one aspect of what we know about space. Spatial cognition
refers to a whole range of mental functions that vary from navigational ability (the
ability to go from point A to point B) to the mental manipulation of complex visual
arrays like those shown in Figure 14-2.
Imagine traveling to an unfamiliar park for a walk. As you walk about the park,
you need to proceed in an organized, systematic way. You do not want to go around
and around in circles. You also need to be able to find your way back to your bus stop.
These abilities require a representation of the physical environment in your mind’s eye.
Now let’s presume that, at some time in the walk, you are uncertain of where you
are (a common problem).One solution is to create a mental image of your route, complete
with various landmarks and turns. It is a small step from mentally manipulating
these kinds of navigational landmarks and movements to manipulating other kinds of
images in your mind. Therefore, the ability to mentally manipulate visual images seems
likely to have arisen in parallel with the ability to navigate in space.
The evolution of skill at mentally manipulating things is also closely tied to the
evolution of physical movements. In the course of evolution, animals likely first moved
by using whole-body movements (such as the swimming motion of a fish), then developed
coordinated limb movements (quadrupedal walking), and finally became capable
of discrete limb movements, such as the reaching movements of human arms.As
the guidance strategies for controlling movements became more sophisticated, cognitive
abilities increased as well to support those guidance systems.
It seems unlikely that more sophisticated cognitive abilities evolved on their own.
For instance, why would a fish be able to manipulate an object in its mind that it could
528 ! CHAPTER 14
Dorsal
stream
Ventral
stream
Figure 14-2
Spatial Cognition These two figures
are the same, but they are oriented
differently in space. Researchers test
spatial cognition by giving subjects pairs
of stimuli like this pair and asking if the
shapes are the same or different.
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not manipulate in the real world? In contrast, a human who can manipulate objects by
hand might be expected to be able to imagine such manipulations.After all,we are constantly
observing our hands manipulating things, and so we must have many mental
representations of such activity. Alex the parrot, although not having hands, manipulates
objects with his beak.
Once the brain can process the manipulation of objects that are physically present,
it seems a small step to picturing the manipulation of objects that are only imagined.
This ability enables us to solve problems like the one depicted in Figure 14-3. The ability
to manipulate an object in the mind’s eye probably flows from the ability to manipulate
tangible objects with the hands.
Which parts of the brain take part in the various aspects of spatial cognition? Some
clues related to spatial navigation come from the study of how children develop navigational
skills. People navigate by using several kinds of information to guide them.
They may take note of single cues or landmarks (a pine tree, a park bench), they may
keep track of their movements (turned left, walked 30 meters), and they may relate observed
landmarks to their own movements (turned right at the bench), thus creating a
spatial representation known as a place response.
Research findings show a progressive change in the type of navigational information
that children use at different ages. In one study, Linda Acredolo (1976) brought
children into a small, nondescript room that had a door at one end, a window at the
other end, and a table along one wall. The children were walked to a corner of the table
and blindfolded.While blindfolded, they were walked in a circuitous route back to the
door. Then the blindfold was removed and they were asked to return to the point at
which they had been blindfolded.
Unbeknown to the children, the table had sometimes been moved. If children used
a place response, they returned to the correct place, even though the table had been
moved. If children used a cue or landmark response, they walked directly to the table,
regardless of where it was positioned. And, if children used a movement response, they
turned in the direction in which they had originally turned when first entering the
room.
Acredolo found that 3-year-olds tend to use a movement response, whereas children
a few years older used a cue or landmark response, and, by age 7, children had
begun to use a place response to find the correct location. This developmental progression
probably mimics the evolutionary progression of spatial cognition. Because
the cortex matures so late in children, it is likely that the cortex controls the more sophisticated
place response in spatial navigation.
Research findings have also provided clues to the brain regions participating in
other aspects of spatial cognition. For instance, the dorsal stream in the parietal lobes
plays a central role in the control of vision for action (Chapter 8). Discrete limb movements
are made to points in space, and so a reasonable supposition is that the evolutionary
development of the dorsal stream provided a neural basis for such spatial
cognitive skills as the mental rotation of objects. In fact, people with damage to the parietal
association regions, especially in the right hemisphere, have deficits in the processing
of complex spatial information, both in the real world and in their imaginations.
If we trace the evolutionary development of the human brain, we find that the
parietal association regions expanded considerably more in humans than in other primates.
This expanded brain region functions, in part, to perform complex spatial operations
such as those just discussed. Humans have a capacity for constructing things
that far exceeds that of our nearest relative, the chimpanzee. A long leap of logic may
be required in making the assertion, but perhaps our increased capacity for building
and manipulating objects played an important role in the evolutionary development
of our spatial cognitive abilities.
HOW DOES THE BRAIN THINK? ! 529
a
b
c
Figure 14-3
Mental Manipulation Try this sample
test item used to measure spatial
orientation. Compare the three cubes on
the right with the one on the left. No
letter appears on more than one face of
a given cube. Which cube—a, b, or c—
could be a different view of the cube on
the left? You can find the correct answer
below.
The answer to the mental manipulation in
Figure 14-3 is a.
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Attention
Imagine going to a football game where you intend to meet some friends. You search
for them as you meander through the crowd in the stadium. Suddenly, you hear the
distinctive laugh of one friend, and you turn to scan in that direction. You see your
group and rush to join them.
This common experience demonstrates the nature of attention, selective narrowing
or focusing of awareness to part of the sensory environment or to a class of stimuli.
Even when you are bombarded by sounds, smells, feelings, and sights, you can still detect
a familiar laugh or spot a familiar face. In other words, you can direct your attention.
“Pay Attention!” describes researchers’ efforts to understand how attention operates.
More than 100 years ago,William James (1890) defined attention in the following
way: “It is the taking possession by the mind in clear and vivid form of one out of what
seem several simultaneous objects or trains of thought.” James’s definition goes beyond
our example of locating friends in a crowd, inasmuch as he notes that we can attend
selectively to thoughts as well as to sensory stimuli.Who hasn’t at some time been so
preoccupied with a thought as to exclude all else from mind? So attention can be directed
inward as well as outward.
530 ! CHAPTER 14
Attention. Selective narrowing or
focusing of awareness to part of the
sensory environment or to a class of
stimuli.
Pay Attention!
Focus on New Research
The brain is clearly capable of processing chemical, mechanical,
and electrical energy and generating a rich experience
of the world that we take for granted. This personal
experience of the world is not simply a matter of registering
the presence of particular stimuli but includes subjective features,
too, such as what it is like to feel happy versus what it
is like to feel surprised.
Such experiences all form what we think of as the
“mind.” Until recently there did not appear to be any simple
way to examine the neurological basis of the mind, and
much of our mental life appeared to be beyond the study of
nosy neuroscientists. But recent advances in cognitive psychology
and cognitive neuroscience have made it possible
to derive some inkling of the nature of our mental life.
One way to approach the problem is to consider how
our experience of the same world changes. For instance, our
subjective experience varies with our frame of mind (e.g.,
whether we are happy or sad), our motivational state (e.g.,
food or sexual activity), and our awareness of different features
of the environment (e.g., color or movement). Marisa
Carrasco and her colleagues (Carrasco, Ling, & Read, 2004)
asked a simple question: Does attention alter the appearance
of visual information?
This question seems simple, but psychologists have debated
it for more than 100 years. Does simply paying attention
to information change how we perceive the information?
Or does attention simply intensify our perception of the
information?
Carrasco and her colleagues developed a method for assessing
phenomenological correlates of attention directly.
Participants were presented with pairs of oriented gratings—
for example, pairs A and B shown here—and asked to report
the orientation of the grating having the higher light–dark
+
+
Pair A
Pair B
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SELECTIVE ATTENTION
Like the neural basis of many other mental processes, the neural basis of attention is
particularly difficult to study. However, research findings on monkeys have identified
neurons in the cortex and midbrain that show enhanced firing rates to particular locations
or visual stimuli to which the animals have been trained to attend. Significantly,
the same stimulus can activate a neuron at one time but not at another, depending on
the monkey’s learned focus of attention.
In the study shown in Experiment 14-2, James Moran and Robert Desimone
(1985) trained monkeys to hold a bar while gazing at a fixation point on a screen. A
sample stimulus (e.g., a vertical red bar) appeared briefly at one location in the visual
field, followed about 500 ms later by a test stimulus at the same location.When the test
stimulus was identical with the initial sample stimulus, an animal was rewarded if it
immediately released the bar that it held in its hand. Each animal was trained to attend
to stimuli presented in one particular area of the visual field and to ignore stimuli in
any other area. In this way, the same visual stimulus could be presented to different regions
of a neuron’s receptive field to test whether the cell’s response varied with stimulus
location.
HOW DOES THE BRAIN THINK? ! 531
contrast. In some trials, as in pair A, the gratings have large
differences in contrast, whereas in others, as in pair B, they
appear to have less or no difference. Thus, the task was to
identify orientation by using information about contrast.
The authors manipulated attention by briefly preceding
one of the two choices with a dot that automatically attracted
a subject’s attention. When the dot was shown in
trials with large differences in contrast, the dot failed to influence
perception. However, when the dot was flashed
on trials in which the contrast difference was small or absent,
the observer’s perception was altered: he or she now
believed that the grating preceded by the dot had higher
contrast.
Thus, attention increased the subjective experience
of contrast. What is intriguing about the study is that the
enhanced attention was covert and not intentional, yet it
nonetheless altered sensory impression. As we learned in
Chapter 2, the brain is creating the sensory world, but our
fantasy world clearly is not static and is influenced by our
unconscious awareness.
Another way to think about our mental world is to
measure brain activity as we experience different sensory
stimuli. For example, changes in cerebral blood flow are
correlated with specific visual or auditory stimuli (Chapter
9). But what about more private mental feelings? Recall
that social exclusion activates specific limbic cortical areas
(see “The Pain of Rejection” on page 389). And what about
individual differences in subjective experience and brain
activity?
Stephan Hamann and his colleagues (2004) measured
the brain activity of males and females to sexually arousing visual
stimuli. Men are generally more interested than women
in sexually arousing visual stimuli and are more responsive to
it. In this study, men and women showed similar brain activity
across most brain regions, but there were large differences in
the amygdala: men showed higher activation than women to
the same stimuli, the difference being larger in the left amygdala
than in the right.
Surprisingly, women actually showed no more activation
in the amygdala for sexually arousing scenes than for
neutral scenes. The difference was not because the women
were not aroused by the stimuli; they reported the stimuli to
be just as arousing as did the men. The mental experience of
the same visual stimulus appears to show a sex-related difference,
which may provide a basis for the greater role of visual
stimuli in male sexual arousal. The results obtained in
the Hamann study do not tell us whether the basis of the sex
difference was experiential or genetic, but they do show that
large individual differences in brain activity can be related
to the same stimulus.
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As the animals performed the task, the researchers recorded the firing of neurons
in visual area V4. Neurons in area V4 are sensitive to color and form, with different
neurons responding to different combinations of these two variables (e.g, a red vertical
bar or a green horizontal bar). Visual stimuli were presented either in the correct
location for a reward or in an incorrect location for no reward.
As diagrammed in the Results section of Experiment 14-2, neurons responded
only when a visual stimulus was in the correct location, even though the same stimulus
was presented in the incorrect location. Before training, the neurons responded to all
stimuli in both locations. This finding tells us that the ability to attend to specific parts
of the sensory world is a property of single neurons. Once again, we see that the neuron
is the computational unit of cognition.
DEFICITS OF ATTENTION
Attention is likely a property of neurons throughout the brain, with some regions playing
a more central role in attention than others. The frontal lobes, for instance, play a
very important part. People with frontal-lobe injuries tend to become overly focused
on environmental stimuli. They seem to selectively direct their attention to an excessive
degree or have difficulty in shifting attention.
The results of studies of these people suggest that the frontal association cortex
plays a critical role in the ability to flexibly direct attention where it is needed. Indeed,
the formation of plans, which you know to be a frontal-lobe function, requires this ability.
In addition, the parietal association cortex plays a key role in other aspects of attention.
This role is perhaps best illustrated by studying the attention deficit referred to
as neglect.
Neglect is a condition in which a person ignores sensory information that should
be considered important. Usually the condition affects only one side of the body, in
which case it is called contralateral neglect. Figure 14-4 shows contralateral neglect in
a dog that would eat food only from the right side of its dish. Neglect is a fascinating
532 ! CHAPTER 14
Monkeys were trained to release a bar when a certain
stimulus was presented in a certain location. The
monkeys learned to ignore stimuli in all other locations.
During performance of this task, researchers recorded
the firing of neurons in visual area V4, which are
sensitive to color and form. Stimuli were presented in
either rewarded or unrewarded locations.
EXPERIMENT 14-2
Question: Can neurons learn to respond selectively to stimuli?
Procedure
Results
Fixation point Stimulus
Before training, neurons responded
to stimuli in all locations.
Neurons can learn to respond selectively
to information in their receptive field.
Conclusion
Strong response
Rewarded location Unrewarded location
Rewarded location Unrewarded location
Pretraining recordings:
Posttraining recordings:
Strong response Baseline response
Strong response
After training, neurons responded only when
the visual stimuli were in the rewarded location.
Contralateral neglect. Ignoring a part
of the body or world on the side opposite
(i.e., contralateral) that of a brain injury.
Extinction. In neurology, neglect of
information on one side of the body
when it is presented simultaneously with
similar information on the other side of
the body.
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symptom because it often entails no damage to
sensory pathways. Rather, the problem is a failure
of attention.
People with damage to the parietal association
cortex of the right hemisphere may have
particularly severe neglect of objects or events
in the left side of their world. For example, one
man dressed only the right side of his body,
shaved only the right side of his face, and read
only the right side of a page (if you can call that
reading). He was capable of moving his left limbs spontaneously, but, when asked to
raise both his arms, he would raise only the right.When pressed, he could be induced
to raise the left arm, but then he would quickly drop it to his side again.
As people with contralateral neglect begin to recover, they show another interesting
symptom, extinction. This symptom refers to the neglect of information on one
side of the body when it is presented simultaneously with similar information on the
other side of the body. Figure 14-5 shows a common clinical test for extinction.
The patient is asked to keep his or her eyes fixed on the examiner’s face and to report
objects presented in one or both sides of the visual field. When presented with
a single object (a fork) to one side or the other, the patient orients himself or herself
toward the appropriate side of the visual field, and so we know that he or she cannot
be blind on either side. But now suppose that two forks are presented, one
on the left and one on the right. Curiously, the patient ignores the fork on
the left and reports that there is one on the right.When asked about the
left side, the patient is quite certain that nothing appeared there and that
only one fork was presented, on the right.
Perhaps the most curious aspect of neglect is that people with it fail
to pay attention not only to one side of the physical world around them
but also to one side of the world that they represent in their minds. We
studied one woman who had complete neglect for everything on her left
side. She complained that she could not use her kitchen, because she
could never remember the location of anything on her left.
We asked her to imagine standing at the kitchen door and to describe
what was in the various drawers on her right and left. She could not recall
anything on her left. We then asked her to imagine walking to the
end of the kitchen and turning around.
We now asked her what was on her right, which had previously been
on her left. She broke into a big smile and tears ran down her face as
she realized that she now knew what was on that side of the room. All she
had to do was reorient her body in her mind’s eye. She later wrote and
thanked us for changing her life, because she was now able to cook again.
Clearly, neglect can exist in the mind as well as in the physical world.
Although complete contralateral neglect is normally associated with
parietal-lobe injury, specific forms of neglect can arise from other injuries.
Ralph Adolphs and his colleagues (2005) described case S. M., a
woman with bilateral amygdala damage, who could not recognize fear in
faces. On further study, the reason was shown to be that S. M. failed to
look at the eyes when she looked at faces; instead, she looked at other facial
features such as the nose. Because fear is most clearly identified in
the eyes and not the nose, she did not identify the emotion. When she
was specifically instructed to look at the eyes, her recognition of fear became
entirely normal. Thus, the amygdala plays a role in directing attention
to the eyes to identify facial expressions.
When shown two identical objects
When shown two kinds of an object
When shown two different objects
Patient
sees only
the object
in his right
visual
Patient sees
the object
in both
visual fields.
Patient
sees only
the object
in his right
visual
field.
Patient’s right
visual field
Patient’s left
visual field
Figure 14-4
Contralateral Neglect in a Dog This
dog had a right hemisphere brain tumor
and would eat the food in the right side
of its dish but ignore food in the left
side.
Figure 14-5
Testing for Extinction A stroke patient
who shows neglect for information
presented to his left responds
differently, depending on whether
objects in the left and right visual fields
are similar or different.
Dennis O’Brien
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Planning
Imagine the following scenario. It ‘s Friday noon and one of your friends proposes that
you go to a nearby city for the weekend to attend a concert. She will pick you up at
6:00 PM and you will drive there together.
Because you are completely unprepared for this invitation and because you are
going to be busy until 4:00, you must rush home at 4:00 and get organized. En route
you stop at a fast food restaurant so that you won’t be hungry on the 2-hour drive. You
also need money, and so you zoom to the nearest ATM.When you get home, you grab
various pieces of clothing appropriate for the concert and the trip. You also pack your
toiletries. You somehow manage to get ready by 6:00, when your friend arrives.
Although the task of getting ready in a hurry may make us a bit harried, most of
us can manage to do it, but people with frontal-lobe injury cannot. To learn why, let’s
consider what the task requires.
1. You have to plan your behavior, which requires selecting from many options.What
do you need to take with you? Money? Then which bank machine is closest and
what is the quickest route to get there? Do you also need something to eat? Then
what is the fastest way to get food on a Friday afternoon?
2. In view of your time constraint, you have to ignore irrelevant stimuli. For instance,
if you pass a sign advertising a sale in your favorite music store, you have to ignore
it and persist with the task at hand.
3. You have to keep track of what you have done already, a requirement especially important
while you are packing. You do not want to forget items or to duplicate
items. You do not want to take four pairs of shoes but no toothbrush, for example.
The general requirements of this task can be described as the temporal (or time)
organization of behavior. You are planning what you need to do and when you need to
do it. Such planning is the general function of the frontal lobes.
But note that, to perform this task, you also need to recognize objects (an occipital-
and temporal-lobe function) and to make appropriate movements with respect to
them (a parietal-lobe function). You can therefore think of the frontal lobes as acting
like an orchestra conductor. The frontal lobes make and read some sort of motor plan
(a kind of motor “score,” analogous to the musical score of a conductor) to organize
behavior in space and time. People with frontal-lobe injuries are simply unable to organize
their behavior.
Performance on the Wisconsin Card Sorting Task provides an example of the kinds
of deficits that frontal-lobe injury creates. Figure 14-6 shows the testing materials. The
subject is presented with the four stimulus cards arrayed at the top. These cards bear
designs that differ in color, form, and number of elements, thus creating three possible
sorting categories to be used in the task.
The subject must sort a deck of cards into piles in front of the various stimulus
cards, depending on the sorting category called for. The correct sorting category is
never stated. The subject is told after placing each card whether the choice that he or
she has made is correct or incorrect.
For example, in one trial, the first correct sorting category is color. Then, after
the subject has sorted a number of cards by color, the correct solution switches,
without warning, to form.When the subject has started to sort by form, the correct
solution again changes unexpectedly, this time to the number of items on each
card. The sorting rule later becomes color again, and so on, with each change in
rule coming unannounced.
Shifting response strategies is particularly difficult for people with frontallobe
lesions, who may continue responding to the original stimulus (color) for as
534 ! CHAPTER 14
Figure 14-6
Wisconsin Card Sorting Test The
subject’s task is to place each card in the
bottom pile under the appropriate card
in the top row, sorting by one of three
possible categories: color, number, or
form. Subjects are never explicitly told
what the corrrect sorting category is,
only whether their responses are correct
or incorrect. After subjects have begun
using one sorting category, the tester
unexpectedly changes to another
category.
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many as 100 cards until the test ends. They may even comment that they know that
color is no longer the correct category, but they continue to sort on the basis of it. As
one such person stated: “Form is probably the correct solution now so this [sorting by
color] will be wrong, and this will be wrong, and wrong again.”Curiously, then, despite
knowing what the correct sorting category is, the frontal-lobe patient is unable to shift
behavior in response to the new external information.
Imitation and Understanding
In all communication—both verbal and nonverbal—the sender and receiver must have
a common understanding of what counts. If a person speaks a word or makes a gesture,
it will be understood only if another person interprets it correctly. To accomplish
this coordination in communication, the processes of producing and perceiving a message
must have some kind of representation common to the brain of the sender and
that of the receiver.
How is this common representation achieved? How do both the sender and the receiver
of a potentially ambiguous gesture, such as a raised hand or a faint smile, have a
common understanding of what that gesture means? Giacomo Rizzolatti and Michael
Arbib (1998) proposed an answer to these questions.
In the frontal lobes of monkeys, they identified neurons that discharge during the
production of active movements of the hand or mouth or both. These neural discharges
do not precede the movements but instead occur in synchrony with them. Because
it would take time for a neural message to go from a frontal lobe to a hand, we
would predict that, if these cells are controlling the movements, they will discharge before
the movements take place. The cells must therefore be recording that the movement
is taking place.
In the course of his studies, Rizzolatti also made the remarkable finding that many
of these neurons discharge when a monkey sees other monkeys make the same movements.
They also discharge when the monkey sees the experimenter make the movements.
Rizzolatti called these “mirror neurons.” A mirror neuron does not respond to
an object, only to a specific observed action. The researchers proposed that mirror neurons
represent actions, whether one’s own or those of others. Such neural representations
could be used both for imitating others’ actions and for understanding the
meaning of those actions, thus enabling appropriate responses.Mirror neurons therefore
provide the link between the sender and the receiver of communication.
Rizzolatti and his colleagues used PET to look for these same neuron populations
in humans. Subjects were asked to watch a movement, to make the same movement,
or to imagine the movement. In each case, a region of the lateral frontal lobe in the left
hemisphere, including Broca’s area, was activated.
Taken together with those of the monkey studies, this finding suggests that primates
have a fundamental mechanism for action recognition. People apparently recognize
actions made by others because the neural patterns produced when the actions
are observed are similar to those produced when they themselves make those same actions.
According to Rizzolatti, the human capacity to communicate with words may
have resulted from a progressive evolution of the mirror-neuron system observed in
the monkey brain. After all, the ability to mimic behaviors, such as dancing and
singing, is central to human culture. The evolution of this capacity was perhaps the
precursor to the evolution of language. For language, the same neurons would recognize
words spoken by others and would produce those same words in speech.
A major difference between humans and monkeys is that the mirror neurons are
localized to the left hemisphere in humans. Although the reason is not immediately
clear, the existence of a unilateral representation may be significant for understanding
HOW DOES THE BRAIN THINK? ! 535
Mirror neuron. Nerve cell that fires
when a monkey observes a specific
action being made by another monkey.
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how language is organized in the brain. If the abilities to mimic and to understand gestures
were present before language developed and if the neural circuits for these abilities
became lateralized, then language would also have become lateralized because the
system on which it is based already existed in the left hemisphere.
STUDYING THE HUMAN BRAIN AND COGNITION
Historically, the functions of the association cortex have been inferred largely from the
study of neurological patients. In recent years, however, many new technologies have
been developed to study cognition in the normal brain. So, in addition to traditional
neuropsychological studies of brain-damaged patients, researchers now have a rich
array of more-modern methods to help them analyze the neural correlates of human
thought. Here we consider some of these research techniques. Using them to study the
neural basis of cognition is often referred to as cognitive neuroscience.
Methods of Cognitive Neuroscience
Beginning in the mid-1800s, physicians such as Paul Broca began to make clinical
observations about the mental activity of people with specific brain injuries. In the
twentieth century, this clinical approach developed into the discipline now called
neuropsychology. Neuropsychological studies consist of analysis of the behavioral
symptoms of people with circumscribed, usually unilateral brain lesions due to stroke,
illness, surgery, or trauma.
Presumably, if a patient shows impairment on some behavioral test, the damaged
area must play a role in that particular behavior. To conclude that the area in question
has a special function, however, requires showing that lesions in other parts of the brain
do not produce a similar deficit. For example, if a temporal-lobe patient is impaired on
a test of verbal memory, we would need to demonstrate that someone with frontal- or
parietal-lobe injury does not have a similar impairment. Neuropsychological studies
typically compare the effects that injuries to different brain regions have on particular
tasks, as illustrated in “Neuropsychological Assessment.”
A second approach to examining human brain function is to measure brain activity
and correlate this measurement with the cognitive activity inferred to be taking
place at the same time. One method of measuring brain activity is to use electrical
recordings, such as the event-related potentials (ERPs) discussed in Chapter 4 (see Figures
4-27 and 4-28).
In Review .
The association cortex contains knowledge about both our external and our internal
worlds and functions to produce the many different forms of cognitive behavior in which
we engage. As a general rule, the temporal lobes generate knowledge about objects,
whereas the parietal lobes produce various forms of spatial cognition. In addition, neurons
in both the temporal and the parietal lobes seem to contribute to our ability to selectively
attend to particular sensory information. The frontal lobes function not only to
make movements but also to plan movements and to organize our behavior over time. In
humans, an area of the left frontal lobe interprets the behavior of others so that the information
can be used to plan appropriate actions.
536 ! CHAPTER 14
Cognitive neuroscience. Study of the
neural basis of cognition.
Neuropsychology. General term used
to refer to the study of the relation
between brain function and behavior.
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HOW DOES THE BRAIN THINK? ! 537
Neuropsychological Assessment
Focus on Disorders
Beginning in the late 1940s and continuing today, neuropsychologists
have devised a battery of behavioral tests designed
to evaluate the functional capacities of different
cortical areas, especially association areas. Although “high
tech” procedures such as PET, fMRI, and ERP also have been
developed, “low tech” behavioral assessment continues to
be one of the best and simplest ways to measure cognitive
function.
To illustrate the nature and power of neuropsychological
assessment, we will compare the test performance of
three patients on five of the tests used in a complete neuropsychological
assessment. The first two are tests of delayed
memory—one verbal, the other visual. The patients were
read a list of words and two short stories. They were also
shown a series of simple drawings. Their task was to repeat
the words and stories immediately after hearing them and to
draw the simple figures. Then, without warning, they were
asked to do so again 30 min later. Their performances on
these delayed tests yield the delayed verbal and visual memory
scores.
The third test is verbal fluency, in which patients were
given 5 min to write down as many words as they could
think of that start with the letter s, excluding people’s names
and numbers. Next is the Wisconsin Card Sorting Test,
which assesses abstract reasoning (see Figure 14-6). Finally,
the patients were given a reading test. For all these tests,
performance was compared with that of a normal control
subject.
The first patient, J. N., was a 28-year-old man who had
developed a tumor in the anterior and medial part of the left
temporal lobe. Preoperative psychological tests showed this
man to be of superior intelligence, with his only significant
deficits being on tests of verbal memory. When we saw him,
1 year after surgery that successfully removed the tumor, he
had returned to his job as a personnel manager. His intelligence
was still superior, but, as the accompanying score
summary shows, he was still impaired on the delayed verbal
memory test, recalling only about 50 percent as much as the
other subjects did.
The second patient, E. B., was a college senior majoring
in psychology. An aneurysm in her right temporal lobe had
burst, and the anterior part of that lobe had been removed.
E. B. was of above-average intelligence and completed her
bachelor of arts degree with good grades. Her residual deficit
was clearly shown on her delayed visual memory test, where
she recalled just a little more than half of what the other subjects
did.
The third patient, J. W., was a 42-year-old police detective
who had a college diploma and also was of aboveaverage
intelligence. He had a benign tumor in the left
frontal lobe. We saw him 10 years after his surgery, at which
time he was still working in the police force, although at a
desk job. His verbal fluency was markedly reduced, as was
his ability to solve the card-sorting task. His reading skill,
however, was unimpaired, which was also true of the other
patients.
Two points can be made from the results of these neuropsychological
assessments. First, damage to different parts
of the brain produces different symptoms, which allows
functions to be localized to different cerebral regions. Second,
brain organization is asymmetrical. Left-hemisphere
damage preferentially affects verbal functions, whereas
right-hemisphere damage preferentially affects nonverbal
functions.
Subjects’ Scores
Test Control J. N. E. B. J. W.
Delayed verbal memory 17 9* 16 16
Delayed visual memory 12 14 8* 12
Verbal fluency 62 62 66 35*
Card-sorting errors 9 10 12 56*
Reading 15 21 22 17
* Abnormally poor score
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Another method is to take advantage of the fact that the electrical currents of
neurons generate tiny magnetic fields.A special recording device known as a SQUID (superconducting
quantum interference device)can record these magnetic fields and produce
a magnetoencephalogram. Like the ERP procedure, magnetoencephalography
(MEG) requires that many measurements be
taken and averaged.
A third approach to the study of human
brain function is to measure brain metabolism,
as in a PET scan, described in Chapter 8. A more
recent, less-invasive alternative is magnetic resonance
imaging (MRI), illustrated in Figure
14-7. MRI is based on the principle that hydrogen
atoms behave like spinning bar magnets in
the presence of a magnetic field.
Normally, hydrogen atoms point randomly
in different directions but,when placed in a magnetic
field, they line up in parallel as they orient
themselves with respect to the field’s lines of
force. In MRI, radio pulses are applied to a brain
whose atoms have been aligned in this manner,
and the radio pulses form a second magnetic
field. This second field causes the spinning atoms
to wobble irregularly, thus producing a tiny electrical
current that the MRI measures.
When the currents are recorded, images of
the brain based on the density of the hydrogen atoms in different
regions can be made. For example, areas of the brain
with a high water (H2O) content (neuron-rich areas) will
stand out from areas with a lower water content (axon-rich
areas). Figure 14-7 shows such a magnetic resonance image.
When a region of the brain is active, the amount of blood flow
and oxygen to it increases. A change in the oxygen content of
the blood alters the spin of the blood’s hydrogen atoms. This alteration, in turn, affects
the MRI signal.
In 1990, Segi Ogawa and his colleagues showed that MRI could accurately match
these changes in magnetic properties to specific locations in the brain (Ogawa et al.,
1990), a process known as functional magnetic resonance imaging (fMRI). Figure
14-8 illustrates changes in the fMRI signal in the visual cortex of a person who is being
stimulated visually.Manipulation of the characteristics of the stimulus (color,motion,
spatial orientation) allows the dissociation of the activity of the various visual areas of
the occipital lobes (the areas shown in Figure 8-17). In other words, fMRI can show
that different visual areas are differentially activated when different types of visual
stimuli are presented.
A major advantage over PET is that fMRI allows the anatomical structure of each
subject’s brain to be identified, and brain activity can then be related to localized
anatomical regions on the brain image. Functional MRI also has better spatial resolution
than does PET. And the actual change in the oxygen signal caused by changes in
blood flow can be monitored.
On the negative side, however, fMRI is expensive. The resolution of standard hospital
MRI is generally insufficient for research purposes, and so neuroscientists need to
buy even more expensive equipment to conduct their specialized research. In addition,
fMRI can be very difficult for subjects to endure. They are required to lie motionless
538 ! CHAPTER 14
Figure 14-7
Magnetic Resonance Imaging
The subject is placed in a long
metal cylinder that has two sets
of magnetic coils arranged at
right angles to each other. An
additional coil, known as a radio
frequency coil, surrounds the
head (not shown) and is designed
to perturb the static magnetic
fields to produce the magnetic
resonance image.
On your CD, investigate more about
MRI, including scans of the brain, in the
module on Research Methods.
Magnetic
coils
Hollow
tube
Bob Schatz/Liaison International
Gregory G. Dimijian/Photo Researchers
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in a long, noisy tube, an experience that can be quite claustrophobic. The confined
space also restricts the types of behavioral experiments that can be performed.
Yet another way to study human brain function is to disrupt brain activity briefly
while a person is performing some task to observe the results.Wilder Penfield used this
procedure when he electrically stimulated the brains of patients who were about to
undergo neurosurgery (Chapter 9). Although much has been learned by using brain
stimulation, it has a major drawback: it can be carried out only on subjects whose
brains are exposed. This requirement makes it impractical as a laboratory research tool.
More recently, a procedure has been developed that can be used on normal subjects.
This technique is called transcranial magnetic stimulation (TMS). A low-frequency
magnetic stimulus placed next to the skull causes a disruption of brain function
in the region immediately adjacent to the magnet. Thus, by placing a small coil over
the skull and using repetitive TMS (rTMS), one can interfere with the neural activity
of the brain regions under the coil.
One reason for this interference is a drop in blood flow in the stimulated area, resulting
in disturbed functioning. In a typical experiment, a region of brain is located
first on an image obtained by MRI.When the coordinates of the region are identified,
the magnetic coil for TMS is put in place.
The Power of Cognitive Neuroscientific Analysis
Thomas Paus and colleagues (1997) combined TMS, PET, and fMRI to produce a very
powerful investigative tool, illustrated in Figure 14-9. Paus first located the motor cortex
by using fMRI. Then a magnetic coil was positioned over that region. The subject
was next placed in a PET scanner, and PET activity was recorded while magnetic stimulation
was applied.
Time (s)
5900
65
5600
Light off Light off
Light on Light on
5750
fMRI signal intensity
6050
0 135 200 270
Baseline
Off Off On On Off Off On On
Figure 14-8
Functional MRI Functional magnetic resonance images showing V1 activation in a normal
human brain during visual stimulation. The occipital pole is at the bottom. A baseline acquired in
darkness (far left) was subtracted from the subsequent images (see Figure 9-22). The subject
wore tightly fitting goggles containing light-emitting diodes that were turned on and off as a
rapid sequence of scans was obtained in a period of 270 s. The images show prominent activity
in the visual cortex when the light is on and rapid cessation of activity when the light is off. The
graph (bottom) illustrates that the on-line fMRI measure can be quantified. Adapted from “Dynamic
Magnetic Resonance Imaging of Human Brain Activity During Primary Sensory Stimulation,” by K. K. Kwong et al.,
1992, Proceedings of the National Academy of Sciences, USA, 89, p. 5678.
Magnetoencephalography (MEG).
Recording of the changes in tiny magnetic
fields generated by the brain.
Magnetic resonance imaging (MRI).
Imaging procedure in which a computer
draws a map from the measured changes
in the magnetic resonance of atoms in the
brain; allows the production of a
structural map of the brain without
actually opening the skull.
Functional magnetic resonance
imaging (fMRI). Type of magnetic
resonance imaging that takes advantage
of the fact that changes in the distribution
of elements such as oxygen alter the
magnetic properties of the brain. Because
oxygen consumption varies with
behavior, changes that are produced by
behavior can be mapped and measured.
Transcranial magnetic stimulation
(TMS). Procedure in which a lowfrequency
magnetic coil is placed over
the skull to stimulate the underlying brain
tissue; can be used either to induce
behavior or to disrupt ongoing behavior
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TMS COIL
L R
4
With the transcranial
magnetic stimulator
in place, the subject
is then placed in a
PET scanner where
cortical activity is
monitored.
3
The TMS coil,
shown here in a
composite MRI
and PET-scan
photograph,
interferes with
brain function
in the adjacent
area.
Brain region is located
with the use of MRI.
1
A transcranial
magnetic stimulator
is placed on the skull
over this region of
the cortex.
2
Figure 14-10
Brain Mapping In this example, TMS was used to stimulate the premotor cortex region that
controls eye movements and is called the frontal eye field (FEF). A TMS coil was then positioned
over that area. Measurement of cerebral blood flow (CBF), by using PET, showed that the TMS
altered blood flow, both at the site of stimulation (the local CBF response) and in the parietal
occipital cortex (PO, the distal CBF response), which reveals the connections between the frontal
and posterior cortical regions. Adapted from “Transcranial Magnetic Stimulation During Positron Emission
Tomography: A New Method for Studying Connectivity of the Human Cerebral Cortex,” by T. Paus, R. Jech, C. J.
Thompson, R. Comeau, T. Peters, and A. Evans, 1997, Journal of Neuroscience, 17, pp. 3178–3184.
Tomas Paus, Montreal Neurological Institute
Tomas Paus, Montreal Neurological Institute
Figure 14-9
Integrated Imaging Technique
Transcranial magnetic stimulation (TMS)
can be used in combination with other
imaging techniques, such as PET or fMRI,
to study cortical functioning. Researchers
such as Tomas Paus use this integrated
technique to locate and to study brain
regions in healthy subjects.
The imaged results are shown in Figure 14-10. The drop in neural activity in the
motor cortex as a result of the magnetic stimulation also affected regions connected
with the motor cortex. When Paus stimulated the frontal eye fields in the premotor
area, he found a decline in blood flow in parietal regions in the dorsal stream that are
presumably connected to the frontal eye fields.
The combination of these three technologies thus allows a novel procedure for
mapping connectivity in the human brain as well as for measuring the effect of TMS
on the performance of particular cognitive activities. Studies using TMS to record cognitive
activity have not yet been reported, but the technique is powerful and will certainly
be used for this purpose in the near future.
The power of cognitive neuroscientific analysis can also be illustrated in an fMRI
study by Dirk Wildgruber and his colleagues (1999). This study was based on the clinical
observation that people with damage to the frontal lobe of either hemisphere often
have difficulty reversing the serial order of items such as digits, the days of the week,
or the months of the year. For instance, when these patients are asked to count or to
list the days or months in a forward direction, they do so with ease but, when asked for
the same information in reverse order (Sunday, Saturday, Friday, and so on), they have
difficulty. The frontal lobes seem to be active during the reverse-serial-order task but
not during the forward task.
To evaluate this hypothesis, fMRI was conducted on normal subjects who silently
recited the names of the months either forward or backward. Figure 14-11 summarizes
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HOW DOES THE BRAIN THINK? ! 541
–10–0 s
0–10 s
40–50 s
50–60 s
Start recitation foward Start recitation backward
Baseline Baseline
Stop recitation Stop recitation
Figure 14-11
Hypothesis Testing with fMRI Summary illustrations of fMRImeasured
cerebral activation when normal subjects were asked to
mentally recite the names of the months either forward (shown on the
left) or backward (shown on the right). (Top row) During the 10-s
period preceding the beginning of the task, but after instructions were
given, there is some fMRI signal in the frontal lobe and posterior
temporal region in the “recite backward” condition, possibly because
subjects are rehearsing. During the verbal command to begin (second
row), the subjects show activation of the temporal auditory areas
bilaterally, with greater activation on the left in the “recite forward”
condition and greater activation in the frontal lobe in the “recite
backward” condition. When the instructions are completed (third row),
activation is seen only in the left posterior temporal region in the
“recite forward” condition, but, in the “recite backward” condition, it
is also seen in the frontal and posterior parietal regions, especially on
the left. (Bottom row) When the subjects hear the instruction to stop,
the temporal auditory areas are once again activated. Adapted from
“Dynamic Pattern of Brain Activation During Sequencing of Word Strings Evaluated by
fMRI,” by D. Wildgruber, U. Kischka, H. Ackermann, U. Klose, and W. Grodd, 1999,
Cognitive Brain Research, 7, pp. 285–294.
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the major findings of the study. The top row shows scans from the right and left hemispheres
when the subjects were lying quietly for 10 s before the task began. The second
row shows scans during the first 10 s after the verbal instructions to start reciting were
given, whereas the third row shows scans during the next 40 to 50 s while the silent
recitation was going on. The bottom row shows scans during the 10 s after the subjects
were told to stop reciting.
Two major results emerge from the study. First, when the subjects heard and analyzed
the verbal instructions, increased blood flow to the temporal auditory areas was
larger in the left (language-processing) hemisphere than in the right. This activation
did not last, however, because the subjects heard nothing new during the task.
Second, reciting the months activated the brain differently, depending on whether
the recitation was in a forward or backward direction. During the forward recitation,
activation was largely restricted to the posterior temporal cortex in the left hemisphere.
During the backward recitation, in contrast, there was bilateral activation of
the frontal and parietal cortex, although activation was greater on the left side. Clearly,
fMRI is a highly valuable method for analyzing changes in brain activity as they take
place.
Although the major goal of the Wildgruber study was to examine the role of the
frontal lobes in serial-ordering tasks, it also showed involvement of the parietal and
posterior temporal regions, as well as a left–right asymmetry in cerebral activity. We
encountered cerebral asymmetry before, particularly in reference to the auditory processing
of language and music in Chapter 9. In the next section, we consider the differential
role of the two hemispheres in thinking.
CEREBRAL ASYMMETRY IN THINKING
A fundamental discovery in behavioral neuroscience was the finding by Broca and his
contemporaries in the mid-1800s that language is lateralized to the left hemisphere. But
the implications of this finding were not really understood until the 1960s, when Roger
Sperry (1968) and his colleagues began to study people who had undergone surgical
separation of the two hemispheres as a treatment for intractable epilepsy. That the two
cerebral hemispheres were more specialized in their functions than researchers had
previously realized soon became apparent.
Popular authors in the 1980s seized on this idea and began to write about “left
brained” and “right brained” people and how left-brained people’s right-hemisphere
skills could supposedly be improved by training to use nonverbal strategies to solve
cognitive problems. Although this type of popularized discussion has declined in recent
years, the concept of cerebral asymmetry is still important to understanding how
In Review .
Analysis of the behavioral symptoms of brain-injured patients began in the late 1800s. In
the twentieth century, this approach developed into the field of neuropsychology. Until
the l990s, neuropsychological assessment was the primary source of insights into how the
human brain thinks. In recent years, however, the development of sophisticated imaging
techniques, including ERP, PET, fMRI, MEG, and TMS, has allowed the development of
cognitive neuroscience, the study of brain activity while subjects perform various cognitive
tasks. By using multiple methods, contemporary researchers can gather converging
evidence on the nature of neural activity during human thought.
542 ! CHAPTER 14
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the human brain thinks. So, before considering how the two sides of the brain cooperate
in generating cognitive activity, we look at the anatomical differences between the
left and right hemispheres.
Anatomical Asymmetry
As you learned in Chapter 9 in examining brain asymmetries related to audition,
the language- and music-related areas of the left and right temporal lobes differ anatomically.
In particular, the primary auditory area is larger on the right, whereas the
secondary auditory areas are larger on the left in most people. Other regions also are
asymmetrical. For instance, the posterior parietal cortex of the right hemisphere is
larger than the corresponding region of the left hemisphere.
Figure 14-12 shows that the lateral fissure, which partly separates
the temporal and parietal lobes, has a sharper upward
course in the right hemisphere relative to the left. The result is that
the posterior part of the right temporal lobe is larger than the
same region on the left side of the brain, as is the left parietal lobe
relative to the right.
There are also anatomical asymmetries in the frontal lobes.
For example, the region of the sensory–motor cortex representing
the face is larger in the left hemisphere than in the right, a difference
that presumably corresponds to the special role of the left hemisphere in talking.
Furthermore, Broca’s area (the frontal operculum) is organized differently on the left
and right. The area visible on the surface of the brain is about one-third larger on the
right than on the left, whereas the area of cortex buried in the sulci of this region is
greater on the left than on the right.
Not only do these gross anatomical differences between the two hemispheres exist
but so, too, do hemispheric differences in the details of cellular and neurochemical
structure. For example, the neurons in Broca’s area on the left have larger dendritic
fields than do the corresponding neurons on the right. The discovery of these structural
asymmetries and others tells us little about why such differences exist. Ongoing
research is now beginning to show that they are due to underlying differences in cognitive
processing by the two sides of the brain.
Although many anatomical asymmetries in the human brain are related to language,
such asymmetries are not unique to humans. Most, if not all, mammals have
brain asymmetries, as do many species of birds. Cerebral asymmetry therefore cannot
simply be present for the processing of language. Rather, human language more likely
evolved after the brain had become asymmetrical. Language simply took advantage of
processes that had already been lateralized by natural selection in earlier members of
the human lineage.
Functional Asymmetry in Neurological Patients
That the two hemispheres of the human brain sometimes specialize in different functions
is shown by studying people with damage to the left or right side of the brain. To
see these functional differences clearly, compare the cases of G. H. and M. M.
When G. H. was 5 years old, he went on a hike with his family and was hit on the
head by a large rock that rolled off an embankment.He was unconscious for a few minutes
and had a severe headache for a few days, but he quickly recovered. By age 18, however,
he had started having seizures.
HOW DOES THE BRAIN THINK? ! 543
Parietal
lobe
Left hemisphere Right hemisphere
Lateral fissure
Temporal
lobe
Figure 14-12
Cerebral Asymmetry The lateral
fissure in the left hemisphere has a
flatter course compared with the lateral
fissure on the right, which takes a more
upward course. As a result, the posterior
part of the right temporal lobe is larger
than the same region on the left side,
and the inferior parietal region is larger
on the left than on the right.
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Neurosurgical investigation revealed that G.H. had suffered a right posterior parietal
injury from the rock accident. The drawing at the top of Figure 14-13 shows the
area affected. After surgery to remove this area, G. H. had weakness of the left side of
his body and showed contralateral neglect. But these symptoms lessened fairly quickly
and, a month after the surgery, they had completely cleared.
Nevertheless, G. H. suffered chronic difficulties in copying drawings and, 4 years
later, he still performed this task at about the level of a 6 year old. He also had trouble
assembling puzzles, which he found disappointing because he had enjoyed doing puzzles
before his surgery.When asked to do tasks such as the one in Figure 14-3, he became
very frustrated and refused to continue.
Finally, he had difficulty finding his way around the city in which he lived. The
general landmarks that he had used to guide his travels before the surgery no longer
seemed to work for him. G. H. now has to learn street names and use a verbal strategy
to go from one place to another.
M. M.’s difficulties were quite different. M. M., a 16-year-old girl, had a meningioma,
which is a tumor of the brain’s protective coverings, the meninges (see “Brain
Tumors” on page 83). The tumor was surgically removed, but it had placed considerable
pressure on the left parietal region, causing damage to the area shown on the bottom
drawing in Figure 14-13.
After the surgery,M.M. experienced a variety of problems. For one thing, she suffered
aphasia, or impairment in the use of language (Chapter 9), although this condition
lessened over time. A year after the surgery, she was able to speak quite fluently.
Unfortunately, her other difficulties persisted.
In solving arithmetic problems, in reading, and even in simply calling objects or animals
by name,M.M. performed at about the level of a 6 year old.When asked to copy a
series of arm movements, such as those illustrated in Figure 14-14, she had great difficulty.
She seemed unable to figure out how to make her arm move to match the example.
She had no difficulty in making movements spontaneously, however, which means
that she was able to move her limbs. Rather, she had a general impairment in copying
movements, which is a symptom of apraxia, a general impairment in making voluntary
movements in the absence of paralysis or a muscular disorder (Chapter 10).
What can we learn about brain function by comparing these two patients? Their
lesions were in approximately the same location but in opposite hemispheres, and their
544 ! CHAPTER 14
Series 1
Series 2
Figure 14-14
Two Arm-Movement Series Subjects
observe the tester perform each
sequence and then copy it as accurately
as they can. People with left-hemisphere
injury, especially in the posterior parietal
region, are impaired at copying such
movements.
Injury to this area of the right
hemisphere caused difficulties
in copying drawings,
assembling puzzles, and finding
the way around a familiar city.
Injury to this area of the left
hemisphere caused difficulties in
language, copying movements,
reading, and generating names
of objects or animals.
Case G. H.
Case M. M.
Figure 14-13
Contrasting Parietal-Lobe Injuries
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symptoms were very different. Judging from the difficulties that G. H. had, the right
hemisphere plays a role in the control of spatial skills, such as drawing, assembling
puzzles, and navigating in space. In contrast, M. M.’s condition reveals that the left
hemisphere seems to play some role in the control of language functions, as well as in
various cognitive tasks related to schoolwork—namely, reading and arithmetic. In addition,
the left hemisphere plays a role in controlling sequences of voluntary movement
that differs from the role of the right hemisphere.
To some extent, therefore, the left and right hemispheres think about different
types of information. The question is whether these differences in function can be observed
in a normal brain.
Functional Asymmetry in the Normal Brain
In the course of studying the auditory capacities of people with temporal-lobe lesions,
Doreen Kimura (1967) came upon an unexpected finding in her normal control
subjects. She presented people with two strings of digits, one played into each ear, a
procedure known as dichotic listening. The subjects’ task was to recall as many of the
digits as possible.
Kimura found that her normal controls recalled more digits presented to the right
ear than to the left. This result is a bit surprising because the auditory system is repeatedly
crossed, beginning in the midbrain. Nonetheless, information coming from
the right ear seems to have preferential access to the left (speaking) hemisphere.
In a later study, Kimura (1973) played two pieces of music, one to each ear. She
then gave subjects a multiple-choice test in which she played four bits of musical selections
and asked the subjects to pick out those that they had heard before. In this test,
she found that normal subjects were more likely to recall the music played to the left
ear than that played to the right ear. This result implies that the left ear has preferential
access to the right (musical) hemisphere.
The demonstration of this functional asymmetry in the normal brain provoked
much interest in the 1970s, leading to demonstrations of functional asymmetries
in the visual and tactile systems as well. Consider the visual system. If we
fixate on a target, such as a dot, all the information to the left of the dot goes to
the right hemisphere and all the information to the right of the dot goes to the left
hemisphere, as shown in Figure 14-15.
If information is presented for a relatively long time—say, 1 s—we can easily
report what was in each visual field. If, however, the presentation is brief—say,
only 40 ms—then the task is considerably harder. This situation allows us to reveal
a brain asymmetry.
Words presented briefly to the right visual field, and hence sent to the left
hemisphere, are more easily reported than are words presented briefly to the left
visual field. Similarly, if complex geometric patterns or faces are shown briefly,
those presented to the left visual field, and hence sent to the right hemisphere, are
more accurately reported than are those presented to the right visual field. Apparently,
the two hemispheres are processing information differently. The left
hemisphere seems to be biased toward processing language-related information,
whereas the right hemisphere seems to be biased toward processing nonverbal, especially
spatial, information.
A word of caution: Although asymmetry studies are fascinating,what they tell
us about the differences between the two hemispheres is not entirely clear. They
tell us that something is different, but it is a long leap to conclude that the two
hemispheres house entirely different kinds of skills.
HOW DOES THE BRAIN THINK? ! 545
Dichotic listening. Experimental
procedure for simultaneously presenting a
different auditory input to each ear
through stereophonic earphones.
Retina
Left visual field Right visual field
“Anne”
Optic
chiasm
Right
hemisphere
Retina
Left
hemisphere
“Anne”
Fixation point
Corpus callosum
Figure 14-15
Visual Pathways to the Two
Hemispheres When fixating at a
point, each eye sees both visual fields
but sends information about the right
visual field only to the left hemisphere
and information about the left visual
field only to the right hemisphere. In
normal subjects given short exposures
to stimuli (well under 1 s), the left
hemisphere is more accurate at
perceiving words, whereas the right
hemisphere is more accurate at
perceiving objects, such as faces.
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Yet this dichotomy was a common thread in popular “left-brain–right-brain” articles
written in the late 1970s and the 1980s. These reports ignored the fact that the two
hemispheres have many functions in common, such as the control of movement in the
contralateral hand and the processing of sensory information through the thalamus.
Still, there are differences in the cognitive operations of the two hemispheres. These differences
can be better understood by studying people whose cerebral hemispheres have
been surgically separated for medical treatment.
The Split Brain
Epileptic seizures may begin in a restricted region of one hemisphere
and then spread through the fibers of the corpus callosum to the corresponding
location in the opposite hemisphere. To prevent the
spread of seizures that cannot be controlled through medication,
neurosurgeons sometimes cut the 200 million nerve fibers of the
corpus callosum. The procedure is medically beneficial for many patients,
leaving them virtually seizure-free with only minimal effects
on their everyday behavior.
In special circumstances, however, the results of a severed corpus
callosum become more readily apparent, as demonstrated
through extensive psychological testing by Roger Sperry, Michael
Gazzaniga, and their colleagues (Sperry, 1968; Gazzaniga, 1970). On
close inspection, these split-brain patients can be shown to have a
unique behavioral syndrome that can serve as a source of insight into
the nature of cerebral asymmetry.
Before a consideration of the details of split-brain studies, let us
make some predictions on the basis of what we already know about
cerebral asymmetry. First, we would expect that the left hemisphere
has language, whereas the right hemisphere does not. Second, we
would expect that the right hemisphere might be better at certain
types of nonverbal tasks, especially those concerning visuospatial
skills.
We might also ask how a severed corpus callosum affects the way
in which the brain thinks. After all, after the corpus callosum has
been cut, the two hemispheres have no way of communicating with
each other. The left and right hemispheres would therefore be free to
think about different things. In a sense, a split-brain patient has two
different brains.
One way to test the cognitive functions of the two hemispheres
in a split-brain patient is to take advantage of the fact that information
in the left visual field goes to the right hemisphere, whereas
information in the right visual field goes to the left hemisphere. Because
the corpus callosum is cut in these patients, information presented
to one side of the brain has no way of traveling to the other
side. It can be processed only in the hemisphere that receives it.
Experiments 14-3 and 14-4 show some basic testing procedures
that use this approach. The split-brain subject fixates on the dot in
the center of the screen while information is presented to the left or
right visual field. The person must make responses with the left hand
(controlled by the right hemisphere),with the right hand (controlled
546 ! CHAPTER 14
EXPERIMENT 14-3
Question: Will severing the corpus callosum affect the way in which the
brain responds?
Procedure
When the left hemisphere, which can speak, sees the spoon
in the right visual field, the subject responds correctly.
When the right hemisphere, which cannot speak, sees the
spoon in the left visual field, the subject does not respond.
Conclusion
The split-brain subject fixates on the dot in the center of
the screen while an image is projected to the left or right
visual field. He is asked to identify verbally what he sees.
If the spoon is presented
to the right visual field,
the subject verbally
answers, “Spoon.”
If the spoon is presented
to the left visual field, the
subject verbally answers,
“I see nothing.”
Screen
Left visual field Right visual field Left visual field Right visual field
Projector
Severed corpus callosum
Results
Split brain. Surgical disconnection of
the two hemispheres in which the corpus
callosum is cut.
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by the left hemisphere), or verbally (which also is a left-hemisphere function). In this
way, researchers are able to observe what each hemisphere knows and what it is capable
of doing.
As illustrated in Experiment 14-3, for instance, a subject might be flashed a picture
of an object—say, a spoon—and asked to state what he or she sees. If the picture
EXPERIMENT 14-4A EXPERIMENT 14-4B
Question: How can the right hemisphere of a
split-brain subject show that it knows information?
Question: What happens if both hemispheres are
asked to respond to competing information?
Procedure Procedure
Results
The split-brain subject is asked to use his left
hand to pick out the object shown on the
screen to the left visual field (right hemisphere).
Each visual field is shown a different
object—a spoon to the left and a pencil to
the right. The split-brain subject is asked to
use both hands to pick up the object seen.
The subject chooses the spoon with his left
hand because the right hemisphere sees the
spoon and controls the left hand. If the right
hand is forced to choose, it will do so by
chance because no stimulus is shown to the
left hemisphere.
Results
In this case, the right and left hands do not
agree. They may each pick up a different
object, or the right hand may prevent the
left hand from performing the task.
Left visual field Right visual field Left visual field Right visual field
Severed
corpus callosum
Severed
corpus callosum
Each hemisphere is capable of responding
independently. The left hemisphere may dominate
in a competition, even if the response is not verbal.
Conclusion
! 547
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is presented to the right visual field, the person will answer, “Spoon.” If the picture is
presented to the left visual field, however, the person will say, “I see nothing.” The patient
responds in this way for two reasons:
1. The right hemisphere (which receives the visual input) does not talk, and so it cannot
respond verbally, even though it sees the spoon in the left visual field.
2. The left hemisphere does talk, but it does not see the spoon, and so it answers—
quite correctly, from its own perspective—that no picture is present.
Now suppose that the task changes. In Experiment 14-4A, the picture of a spoon
is still presented to the left visual field, but the subject is asked to use the left hand to
pick out the object shown on the screen. In this case, the left hand, controlled by the
right hemisphere, which sees the spoon, readily picks out the correct object. Can the
right hand also choose correctly? No, because it is controlled by the left hemisphere,
which cannot see a spoon on the left. If the person is forced in this situation to select
an object with the right hand, the left hemisphere does so at random.
Now let’s consider an interesting twist. The Procedure for Experiment 14-4B is to
show each hemisphere a different object—say, a spoon to the right hemisphere and a
pencil to the left. The subject is asked to use both hands to pick out the object seen.
The problem here is that the right hand and left hand do not agree.While the left hand
tries to pick up the spoon, the right hand tries to pick up the pencil or tries to prevent
the left hand from performing the task.
This conflict between the hemispheres can be seen in the everyday behavior of
some split-brain subjects. One woman, P. O. V., reported frequent interhemispheric
competition for at least 3 years after her surgery. “I open the closet door. I know what
I want to wear. But as I reach for something with my right hand,my left comes up and
takes something different. I can’t put it down if it’s in my left hand. I have to call my
daughter.”
We know from Experiment 14-3 that the left hemisphere is capable of using
language, but what functions does the right hemisphere control? Other split-brain
studies have attempted to answer this question. Investigations into the visuospatial capacities
of the two hands were sources of some of the first insights.
For example, one split-brain subject was presented with several blocks, each having
two red sides, two white sides, and two half-red and half-white sides, as illustrated
in the Procedure section of Experiment 14-5. The task was to arrange the blocks to
form patterns identical with those shown on cards. When the subject used his right
hand to perform the task, he had great difficulty. His movements were slow and hesitant.
In contrast, when he did the task with his left hand, his solutions were not only
accurate but quick and decisive.
Findings from other studies of split-brain patients have shown that, as tasks of
this sort become more difficult, the left-hand superiority increases. Normal subjects
perform equally well with either hand, indicating the connection between the two
hemispheres. But, in split-brain subjects, each hemisphere must work on its own. Apparently,
the right hemisphere has visuospatial capabilities that the left hemisphere
does not.
Once again, however, some caution is needed. Although findings from studies of
split-brain patients in the past 35 years have shown that the two hemispheres process
information differently, there is more overlap in function between them than was at
first suspected. For instance, the right hemisphere does have some language functions,
and the left hemisphere does have some spatial abilities. Nonetheless, the two sides are
undoubtedly different.
548 ! CHAPTER 14
…but, with his left hand, he
performs the task correctly.
The split-brain patient is unable to
duplicate the pattern by using his
right hand…
The subject is asked to arrange the
blocks so that they duplicate the
pattern shown on the card.
Blocks
Sample
card
The right hemisphere is superior at
visuospacial processing.
Conclusion
Question: How does each hemisphere perform
on a visuospatial construction task?
EXPERIMENT 14-5
Procedure
Results
Adapted from Cognitive Neuroscience: The Biology
of the Mind (p. 323), by M. S. Gazzaniga, R. B. Ivry,
and G. R. Mangun, 1999, New York: Norton.
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Explaining Cerebral Asymmetry
Various hypotheses have been proposed to explain hemispheric differences. One idea,
which dates back a century, is that the left hemisphere plays an important role in the
control of fine movements. Recall M. M., the meningioma patient with left-parietallobe
damage who suffered apraxia. Although that condition subsided, she was left with
a chronic difficulty in copying movements.
So perhaps one reason that the left hemisphere has a role in language is that the
production of language requires fine motor movements of the mouth and tongue. Significantly,
damage to the language-related areas of the left hemisphere
almost always interferes with both language and movement, regardless
of whether the person uses oral language or sign language. Reading
Braille, however,may not be so affected by left-hemisphere lesions.
People use the left hand to read Braille, which is essentially a spatial pattern, and so
processes related to reading Braille may reside in the right hemisphere.
Another clue that the left hemisphere’s specialization for language may be related
to its special role in controlling fine movements comes from the study of where certain
parts of speech are processed in the brain. Recall that cognitive systems for representing
abstract concepts are likely to be related to systems that produce more-concrete behaviors.
Consequently, we might expect that the left hemisphere would have a role in
forming concepts related to fine movements.
Concepts that describe movements are the parts of speech that we call verbs. Interestingly,
a fundamental difference between left- and right-hemisphere language abilities
is that verbs seem to be processed only in the left hemisphere, whereas nouns are
processed in both hemispheres. In other words, not only does the left hemisphere have
a special role in controlling the production of actions, but it also controls the production
of mental representations of actions in the form of words.
If the left hemisphere excels at language because it is better at controlling fine
movements, what is the basis of the right hemisphere’s abilities? One idea is that the
right hemisphere has a special role in controlling movements in space. In a sense, this
role is an elaboration of the functions of the dorsal visual stream.
Once again, we can propose a link between movement at a concrete level and at a
more abstract level. If the right hemisphere is producing movements in space, then it
is also likely to produce mental images of such movements. We would therefore predict
that right-hemisphere patients would be impaired both at making spatially guided
movements and at thinking about such movements. Significantly, they are.
Bear in mind that theories about the reasons for hemispheric asymmetry are
highly speculative. Because the brain has evolved to produce movement and to create
a sensory reality, the observed asymmetry must be somehow related to these overriding
functions. In other words, more recent functions, such as language, are likely to be
extensions of preexisting functions. The fact that language is represented asymmetrically
does not mean that the brain is asymmetrical because of language.After all, brains
are asymmetrically organized in other species that do not talk.
The Left Hemisphere, Language, and Thought
We end our examination of brain asymmetry by considering one other provocative
idea. Michael Gazzaniga (1992) proposed that the superior language skills of the
left hemisphere are important in understanding the differences in thinking between
humans and other animals. He called the speaking hemisphere the “interpreter.”
HOW DOES THE BRAIN THINK? ! 549
Connect to the Web site at www.
worthpublishers.com/kolb/
chapter14 for links to more sites about
split-brain patients.
h
Braille
ou s e
Rotate the hemispheres and
investigate the location of language on
the CD in the module on the Central
Nervous System.
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What he meant is illustrated in the following experiment, using split-brain patients
as subjects.
Each hemisphere is shown the same two pictures, such as a picture of a match followed
by a picture of a piece of wood. A series of other pictures is then shown, and the
task is to pick out a third picture that has an inferred relation to the other two. In our
example, the third picture might be a bonfire. The right hemisphere is incapable of
making the inference that a match struck and held to a piece of wood could create a
bonfire, whereas the left hemisphere can easily arrive at this interpretation.
An analogous task uses words. For example, one or the other hemisphere might be
shown the words pin and finger and then be asked to pick out a third word that is related
to the other two. In this case, the correct answer might be bleed.
The right hemisphere is not able to make this connection. Although it has enough
language ability to pick out close synonyms for pin and finger (needle and thumb, respectively),
it cannot make the inference that pricking a finger with a needle will result
in bleeding. Again, the left hemisphere has no difficulty with this task. Apparently, the
language capability of the left hemisphere gives it a capacity for interpretation that the
right hemisphere lacks. One reason may be that language serves to label and express
the computations of other cognitive systems.
Gazzaniga goes even farther.He suggests that the addition of the language abilities
possessed by the left hemisphere makes humans a “believing” species. That is, humans
can now make inferences and have beliefs about sensory events.
In contrast, Alex, the gray parrot, would not be able to make inferences or hold
beliefs about things, because he does not have a system analogous to our left-hemisphere
language system. Alex can use language but does not make inferences about
sensory events with language. Gazzaniga’s idea is certainly intriguing. It implies a fundamental
difference in the nature of cerebral asymmetry, and therefore in the nature
of cognition, between humans and other animals because of the nature of human
language.
VARIATIONS IN COGNITIVE ORGANIZATION
No two brains are identical. Brains differ in gyral patterns, cytoarchitectonics, vascular
patterns, and neurochemistry, among other things. Some of these differences are genetically
determined, whereas others are due to plastic changes such as those created
by experience and learning. Some brain differences are idiosyncratic, or unique to a
particular person,whereas many other variations are systematic and common to whole
categories of people. In this section, we consider two systematic variations in brain organization,
those related to sex and handedness, and one idiosyncratic variation.
In Review .
The two cerebral hemispheres process information differently, which means that they
think differently. In particular, the right hemisphere plays a role in spatial movements
and spatial cognition as well as in music. The left hemisphere plays a role in the control
of voluntary movement sequences and in language. The addition of verbal mediation
to left-hemisphere thinking may confer a fundamental advantage to the left
hemisphere because language can label the computations of the brain’s various cognitive
systems. As a result, the left hemisphere is able to make inferences that the right
hemisphere cannot.
550 ! CHAPTER 14
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Sex Differences in Cognitive Organization
Popular media are rife with the idea that men and women think differently, and there
seems to be some scientific basis to this view. Books, such as one by Doreen Kimura
(1999), compile considerable evidence for the existence of marked sex differences in
the way in which men and women perform on many cognitive tests. For example,
paper-and-pencil tests consistently show that, on average, females have better verbal
fluency than males do, whereas males do better on tests of spatial reasoning, as illustrated
in Figure 14-16. Our focus here is on how such differences relate to the brain.
NEURAL BASIS OF SEX DIFFERENCES
Many investigators have searched without success for gross differences in the structures
of the male and female cortices. If such differences exist, they must be subtle. There is
stronger indication, however, that gonadal hormones influence the structure of cells in
the brain, including cortical cells.
For example, the structures of neurons in the prefrontal cortices of rats were found
to be influenced by gonadal hormones (Kolb & Stewart, 1991).The cells in one prefrontal
region, located along the midline, have larger dendritic fields (and presumably more
synapses) in males than in females, as shown in the top row of Figure 14-17. In contrast,
the cells in the orbitofrontal region have larger dendritic fields (and presumably more
synapses) in females than in males, as shown in the bottom row.These sex differences are
HOW DOES THE BRAIN THINK? ! 551
(A) Spatial relation–type task
Waterline Correct
response
Incorrect
response
Subjects were asked to
draw a line to indicate
waterline in tipped glass.
(B) Mental rotation–type task
Plan
a
Subjects were asked to choose the
block that could be made from a plan.
Males are generally more accurate
than females at this task.
b c d
(C) Short-term-memory–type task
Subjects were asked to fill in the
empty boxes with the appropriate
symbols from the top row.
When given a larger number of boxes to fill
in and a time limit, females complete from
10 to 20 percent more items than males do.
(D) Verbal-fluency–type task
Subjects were asked to fill in each blank
to form words that make a sentence.
Females are generally faster at
this type of test than males are.
1
2 8 3 2 1 4 2 3 5 9 2 1 7 3 6
9
1. F
7 2 3 1 4 6 1 9 7 4 3 1 6 8
2 3 4 5 6 7 8 9
M A J
2. C B E S
3. D I J K
This response indicates no comprehension of
the concept of horizontality of fluid level.
Males are generally more accurate at making
this judgment than are females.
Figure 14-16
Tasks That Reliably Show Sex-Related
Cognitive Differences (A) On this
spatial-relations task, the incorrect
response was given by about two-thirds
of female subjects. (B) Men typically find
mental rotation tasks much easier than
women do. (C) In tests of short-term
memory with a time limit, women
typically complete from 10 percent to 20
percent more items than men do. (D) As
a rule, women are faster at verbal
fluency tests than men are.
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not found in rats that have had their gonads or ovaries removed at birth.
Presumably, sex hormones somehow change the brain’s organization and
ultimately its cognitive processing.
Findings from a second study showed that the presence or absence
of gonadal hormones affects the brain not only in early development
but also in adulthood. In the course of this study, which focused on how
hormones affect recovery from brain damage, the ovaries of middleaged
female rats were removed (Stewart & Kolb, 1994).When the brains
of these rats and those of control rats were examined some months
later, the cortical neurons (especially the prefrontal neurons) of rats
whose ovaries had been removed had undergone structural changes.
Specifically, the cells had grown 30 percent more dendrites and their
spine density increased compared with the cells in control rats. Clearly,
gonadal hormones can affect the neural structure of the brain at any
point in an animal’s life.
What do these hormonal effects mean in regard to how neurons
process information and, ultimately, how the brain thinks? One possibility
is that gonadal hormones may influence the way in which experience
changes the brain. Evidence in support of this possibility came from a
study by Robbin Gibb and her colleagues (Gibb, Gorny, & Kolb, 2005).
These investigators placed male and female rats in complex environments
like those described in Chapter 13. After 4 months, they examined
the animals’ brains and found a sex difference in the effects of experience.
Both sexes showed experience-dependent changes in neural structure, but the details
of those changes were different.
Females exposed to the enriched environment showed a greater increase in dendritic
branching in the cortex, whereas males housed in the same environment showed
a greater increase in spine density. In other words, although the brains of both sexes
were changed by experience, they were changed in different ways, which were presumably
mediated by the animals’ exposure to different gonadal hormones. These differences
almost certainly affect cognitive processing in one sex relative to the other,
although exactly how is a matter for speculation.
Another way to investigate the effects of sex hormones on how neurons process information
is to relate differences in hormone exposure to particular human cognitive
abilities. This type of study presents obvious problems, because we cannot control hormone
types and levels in people.We can, however, take advantage of naturally occurring
hormone variations within a single sex.
Using these naturally occurring variations is rather simple to do in women.We can
use the age of onset of the first menstrual cycle (known as menarche) as a marker for
the presence of female gonadal hormones. Because this age varies considerably (from
as early as 8 years old to as late as 18), there is ample opportunity to relate the presence
of female hormones to women’s cognitive abilities.
In a study by Sharon Rowntree (2005), girls had been recruited at age 8 to take part
in a 10-year longitudinal study of the relation between age at menarche and body type.
The age at which each started to menstruate was known to within 1 month. At age 16,
all the subjects were given tests of verbal fluency (such as writing in 5 min as many
words as possible that start with the letter d) and of spatial manipulation (such as the
one illustrated in Figure 14-3).
Rowntree reasoned that, if hormones alter cortical neurons, then the age at which
the neurons are changed may influence cognitive processing, which is exactly what she
found evidence for, as summarized in Figure 14-18. Specifically, girls who reached
menarche earlier (age 12 or younger) were generally better at the verbal tasks than were
552 ! CHAPTER 14
Cells from medial
frontal cortex
Cells from orbitofrontal
region
Male rat Female rat
Figure 14-17
Sex Differences in the Architecture of
Neurons In the frontal cortices of male
and female rats, cells in the midline
frontal region (shown by arrows in the
top two drawings) are more complex in
males than in females, whereas the
opposite is true of the orbitofrontal
region (shown by arrows in the bottom
two drawings).
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girls who began to menstruate later, whereas girls who reached menarche later were
generally better at the spatial tasks. In short, the age at which gonadal hormones affect
the brain may be the critical factor in the development of cognitive skills.
This idea has been examined in another way by Deborah Waber (1976). She did a
retrospective study in which age at puberty was estimated in both boys and girls. She
found that, regardless of sex, early-maturing adolescents performed better on tests of
verbal abilities than they did on tests of spatial abilities, whereas late-maturing subjects
showed the opposite pattern.
Waber argued that sex differences in mental abilities are due to differences in the
organization of cortical function that are related to differential rates of physical maturation.
Because boys usually mature later than girls, they show a different pattern of
cognitive skills from that of girls.
The advantage of using same-sex subjects in such studies is to reduce the probability
that different experiences before puberty account either for the girls’ age differences
at menarche or for their different cognitive abilities. Rather, the gonadal hormones of
puberty seem more likely to influence the structure of cortical neurons and, ultimately,
cognitive processing.
The postpubertal experiences of the girls could have affected the brains of early
maturers differently from those of late maturers, but gonadal hormones would still
have played an important mediating role. Interestingly, boys reach puberty later than
girls, and boys, on average, do better at spatial tasks and worse on verbal tasks than girls
do. Perhaps the age at which hormones affect the brain is the critical factor here.
An additional way to consider the neural basis of sex differences is to look
at the effects of cortical injury in men and women. If there are sex differences
in the neural organization of cognitive processing, there
ought to be differences in the effects of cortical injury in the two
sexes. In fact, Doreen Kimura (1999) conducted this kind of study
and showed that the pattern of cerebral organization within each
hemisphere may differ between the sexes.
Investigating people who had sustained cortical strokes in
adulthood, Kimura tried to match the location and extent of injury
in her male and female subjects. She found that, although men and
women were almost equally likely to be aphasic subsequent to lefthemisphere
lesions of some kind,men were more likely to be aphasic
and apraxic after damage to the left posterior cortex, whereas
women were far more likely to be aphasic and apraxic after lesions
to the left frontal cortex. These results, summarized in Figure 14-19,
suggest a difference in intrahemispheric organization between the
two sexes.
HOW DOES THE BRAIN THINK? ! 553
Early-maturing girls show
higher verbal fluency
than later-maturing girls.
Late-maturing girls show
higher spatial ability than
earlier-maturing girls.
50
20
Mean number of words
45
40
35
30
25
Early Late
Word fluency
18
16
14
12
1086420
Mean correct rotations
Early Late
Mental rotation
Figure 14-18
Effects of Sex Hormones Girls who
reach menarche early (before age 12)
have better verbal skills but weaker
spatial skills than do girls who reach
menarch late (after age 14). Data courtesy
of S. Rowntree, from “Spatial and Verbal Ability
in Adult Females Vary with Age at Menses,” by
S. Rowntree, 2005, manuscript in preparation.
KEY
Females
Males
Apraxia
Left frontal
area
Left posterior
area
0
20
40
60
Sex-related frequency (%)
80
Aphasia
Left frontal
area
Left posterior
area
0
20
40
60
80
Broca’s
area
Area of stroke
Wernicke’s
area
Figure 14-19
Evidence for Intrahemispheric
Differences in Cortical Organization
of Men and Women Apraxia is
associated with frontal damage to the
left hemisphere in women and with
posterior damage in men. Aphasia
occurs most often when damage is to
the front of the brain in women but in
the rear of the brain in men. Adapted from
Sex and Cognition, by D. Kimura, 1999,
Cambridge, MA: MIT Press.
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EVOLUTION OF SEX-RELATED COGNITIVE DIFFERENCES
Although emphasis has been on the role of gonadal hormones to explain sex differences
in cognitive function, we are still left with the question of how these differences
arose in the first place. To answer this question, we must look back at human
evolution. Ultimately, males and females of a species have virtually all their genes in
common. Mothers pass their genes to both sons and daughters, and fathers do the
same.
The only way in which a gene can affect one sex preferentially is for that gene’s activities
to be influenced by the animal’s gonadal hormones, which in turn are determined
by the presence or absence of the Y chromosome. The Y chromosome carries a
gene called the testes-determining factor (TDF). This gene stimulates the body to produce
testes, which then manufacture androgens, which subsequently influence the activities
of other genes.
Like other body organs, the brain is a potential target of natural selection. We
should therefore expect to find sex-related differences in the brain whenever the two
sexes differ in the adaptive problems that they have faced in the evolutionary history
of the species. The degree of aggressive behavior produced by the brain is a good
example.
Males are more physically aggressive than females in most mammalian species.
This trait presumably improved males’ reproductive success, reinforcing natural selection
for greater aggressiveness in males. Producing higher levels of aggression entails
male hormones. We know from studies of nonhuman species that aggression is
related directly to the presence of androgens and to the effects of these hormones on
gene expression both during brain development and later in life. In this case, therefore,
natural selection has worked on gonadal hormone levels to favor aggressiveness
in males.
Explaining sex-related differences in cognitive processes, such as language or spatial
skills, is more speculative than explaining sex-related differences in aggressive behavior.
Nevertheless, some hypotheses come to mind. For instance, we can imagine
that, in the history of mammalian evolution, males have tended to range over larger
territories than females have. This behavior requires spatial abilities, and so the development
of these skills would have been favored in males.
Support for this hypothesis comes from comparing spatial problem-solving abilities
in males of closely related mammalian species—one in which the males range over
large territories versus one in which the males do not have such extensive ranges. For
example, pine voles have restricted ranges and no sex-related difference in range,
whereas meadow voles have ranges about 20 times as large as those of pine voles, with
the males ranging more widely than the females.
When the spatial skills of pine voles and meadow voles are compared, meadow
voles are far superior. Furthermore, among meadow voles, there is a sex difference in
spatial ability that favors males, but no such sex difference exists among pine voles. Recall
from Chapter 13 that the hippocampus is implicated in spatial navigation skills.
Significantly, the hippocampus is larger in meadow voles than in pine voles, and it is
larger in meadow vole males than in females (Gaulin, 1992). A similar logic could help
explain sex-related differences in spatial abilities between human males and females.
Explaining sex-related differences in language skills also is speculative. One hypothesis
holds that, if males were hunters and often away from home, the females left
behind in social groups would be favored to develop tools for social interaction, one of
which is language. It might also be argued that females were selected for fine motor
skills (such as foraging for food and making clothing and baskets). Because of the relation
between language and fine motor skills, enhanced language capacities might
have evolved as well in females.
554 ! CHAPTER 14
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Although such speculations are interesting, they are not testable. We will probably
never know with certainty why sex-related differences in brain organization
developed.
Handedness and Cognitive Organization
Nearly everyone prefers one hand over the other for writing or throwing a ball. Most
people prefer the right hand. In fact, left-handedness has historically been viewed as
odd. Left-handedness, however, is not rare.An estimated 10 percent of the human population
worldwide is left-handed. This proportion represents the number of people
who write with the left hand.When other criteria are used to determine left-handedness,
estimates range from 10 percent to 30 percent of the population.
Because the left hemisphere controls the right hand, right-handedness has generally
been assumed to be somehow related to the presence of speech in the left hemisphere.
If this were so, then language would be located in the right hemispheres of
left-handed people. This hypothesis is easily tested, and it turns out to be false.
In the course of preparing epileptic patients for surgery to remove the abnormal
tissue causing their seizures, Ted Rasmussen and Brenda Milner (1977) injected the left
or right hemisphere with sodium amobarbital (see “The Sodium Amobarbital Test” on
page 556). This drug produces a short-acting anesthesia of the entire hemisphere,making
possible a determination of where speech is located. For instance, if a person becomes
aphasic when the drug is injected into the left hemisphere but not when the drug
is injected into the right, then speech must be in that person’s left hemisphere.
Rasmussen and Milner found that virtually all right-handed people had speech in
the left hemisphere, but the reverse was not true for left-handed people. About 70 percent
of left-handers also had speech in the left hemisphere.Of the remaining 30 percent,
about half had speech in the right hemisphere and half had speech in both hemispheres.
Findings from anatomical studies have subsequently shown that left-handers with
speech in the left hemisphere have anatomical asymmetries similar to those of righthanders.
In contrast, left-handers with speech located in the right hemisphere or in
both hemispheres—known as anomalous speech representation—have either a reversed
anatomical asymmetry or no obvious anatomical asymmetry at all.
Sandra Witelson and Charlie Goldsmith (1991) asked whether there might be any
other gross differences in the structure of the brains of right- and left-handers. One
possibility is that the connectivity of the cerebral hemispheres may differ. To test this
idea, the investigators studied the hand preference of terminally ill subjects on a variety
of one-handed tasks.
They later did postmortem studies of the brains of these patients, paying particular
attention to the size of the corpus callosum. They found that the corpus callosum’s
cross-sectional area was 11 percent greater in left-handed and ambidextrous (no hand
preference) people than in right-handed people.Whether this enlarged callosum is due
to a greater number of fibers, to thicker fibers, or to more myelin remains to be seen. If
the larger corpus callosum is due to a greater number of fibers, the difference would be
on the order of 25 million more fibers. Presumably, such a difference would have major
implications for the organization of cognitive processing in left- and right-handers.
Synesthesia
Some systematic variations in brain organization are idiosyncratic. Synesthesia is the
capacity to join sensory experiences across sensory modalities, as discussed in “A Case
of Synesthesia” on page 557. Examples of this rare capacity include the ability to hear
HOW DOES THE BRAIN THINK? ! 555
Anomalous speech representation.
Condition in which a person’s speech
zones are located in the right hemisphere
or in both hemispheres.
Synesthesia. Ability to perceive a
stimulus of one sense as the sensation of
a different sense, such as when sound
produces a sensation of color.
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556 ! CHAPTER 14
The Sodium Amobarbital Test
Focus on Disorders
Guy, a 32-year-old lawyer, had a vascular malformation over
the region corresponding to the posterior speech zone. The
malformation was beginning to cause neurological symptoms,
including epilepsy. The ideal surgical treatment was removal
of the abnormal vessels.
The problem was that the removal of vessels sitting over
the posterior speech zone poses a serious risk of permanent
aphasia. Because Guy was left-handed,
his speech areas could be in the right
hemisphere. If so, the surgical risk
would be much lower.
To achieve certainty in such doubtful
cases, Jun Wada and Ted Rasmussen
(1960) pioneered the technique of injecting
sodium amobarbital, a barbiturate,
into the carotid artery to produce a
brief period of anesthesia of the ipsilateral
hemisphere. (Injections are now normally
made through a catheter inserted
into the femoral artery.) This procedure
enables an unequivocal localization of
speech, because injection into the
speech hemisphere results in an arrest of
speech lasting as long as several minutes.
As speech returns, it is characterized by
aphasic errors.
Injection into the nonspeaking hemisphere
may produce no or only brief
speech arrest. The amobarbital procedure
has the advantage of allowing each hemisphere to be studied
separately in the functional absence of the other (anesthetized)
hemisphere. Because the period of anesthesia lasts
several minutes, a variety of functions, including memory
and movement, can be studied to determine a hemisphere’s
capabilities.
The sodium amobarbital test is always performed bilaterally,
with the second cerebral hemisphere being injected
several days after the first one to make sure that there is no
residual drug effect. In the brief period of drug action, the
patient is given a series of simple tasks requiring the use
of language, memory, and object recognition. Speech is
tested by asking the patient to name some common objects
presented in quick succession, to count and to recite the
days of the week forward and backward, and to spell simple
words.
If the injected hemisphere is nondominant
for speech, the patient may continue
to carry out the verbal tasks, although there
is often a period as long as 30 s during
which he or she appears confused and is
silent but can resume speech with urging.
When the injected hemisphere is dominant
for speech, the patient typically stops talking
and remains completely aphasic until
recovery from the anesthesia is well along,
somewhere in the range of 4 to 10 min.
Guy was found to have speech in the
left hemisphere. During the test of his left
hemisphere, he could not talk. Later, he
said that, when he was asked about a particular
object, he wondered just what that
question meant. When he finally had some
vague idea, he had no idea of what the answer
was or how to say anything. By then
he realized that he had been asked all sorts
of other questions to which he had also not
responded.
When asked which objects he had been shown, he said
he had no idea. However, when given an array of objects
and asked to choose with his left hand, he was able to identify
the objects by pointing, because his nonspeaking right
hemisphere controlled that hand. In contrast, his speaking
left hemisphere had no memory of the objects, because it
had been asleep.
To avoid damaging the speech zones
of patients about to undergo brain
surgery, surgeons inject sodium
ambobarbital into the carotid artery.
The sodium amobarbital anesthetizes
the hemisphere where it is injected (in
this case, the left hemisphere), allowing
the surgeon to determine if that
hemisphere is dominant for speech.
Left carotid
artery
Sodium
amobarbital
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colors and to taste shapes. Richard Cytowic (1998) estimated that the incidence of
synesthesia is about 1 in every 25,000 people.
Synesthesia runs in families, the most famous case being the family of Russian novelist
Vladimir Nabokov. As a toddler, Nabokov complained to his mother that the letter
colors on his wooden alphabet blocks were “all wrong.”His mother understood what he
meant, because she too perceived letters and words in particular colors. Nabokov’s son
is synesthetic in the same way. Perhaps one example of synesthesia that is quite common
is the “shivering” sensation on one’s back produced by certain sounds.
Such sensory blendings are difficult for most of us to imagine. We wonder how
sounds or letters could possibly produce colors, but there is little doubt that synesthesia
exists. Studies of people with this sensory ability show that the same stimuli always
elicit the same synesthetic experiences for them.
The most common form of synesthesia is colored hearing. For many synesthetics,
colored hearing means that they hear both speech and music in color, the experience
being a visual melange of colored shapes, movement, and scintillation. The fact that
colored hearing is more common than other types of synesthesia is curious.
HOW DOES THE BRAIN THINK? ! 557
A Case of Synesthesia
Focus on Disorders
Michael Watson tastes shapes. He first came to the attention
of neurologist Richard Cytowic when they were having dinner
together. After tasting a sauce that he was making for
roast chicken, Watson blurted out, “There aren’t enough
points on the chicken.”
When Cytowic quiz zed him about this strange remark,
Watson said that all flavors had shape for him. “I wanted the
taste of this chicken to be a pointed shape, but it came out
all round. Well, I mean it’s nearly spherical. I can’t serve this
if it doesn’t have points” (Cytowic, 1998, p. 4).
Watson has synesthesia, which literally means “feeling
together.” All his life Watson has experienced the feeling of
shape when he tastes or smells food. When he tastes intense
flavors, he reports an experience of shape that sweeps down
his arms to his fingertips. He experiences the feeling of
weight, texture, warmth or cold, and shape, just as though
he was grasping something.
The feelings are not confined to his hands, however.
Some taste shapes, such as points, are experienced over his
whole body. Others are experienced only on the face, back,
or shoulders. These impressions are not metaphors, as other
people might use when they say that a cheese is “sharp” or
that a wine is “textured.” Such descriptions make no sense
to Watson. He actually feels the shapes.
Cytowic systematically studied Watson to determine
whether his feelings of shape were always associated with
particular flavors and found that they were. Cytowic devised
the set of geometric figures shown here to allow Watson
to communicate which shapes he associated with various
flavors.
Neurologist Richard Cytowic devised this set of figures to help
Michael Watson communicate the shapes that he senses when he
tastes food.
1
2
3 4
5
23
22 21
20
19
18
17
16
15
14
6
7
8
9
10
11
12
13
Experience some simulations of
synesthesia on the Web site at www.
worthpublishers.com/kolb/
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There are five primary senses (vision, hearing, touch, taste, and smell), and so, in
principle, there ought to be 10 possible synesthetic pairings. In fact, however, most
pairings are in one direction. For instance, whereas synesthetic people may see colors
when they hear, they do not hear sounds when they look at colors. Furthermore, some
sensory combinations occur rarely, if at all. In particular, taste or smell rarely triggers
a synesthetic response.
The neurological basis of synesthesia is difficult to study because each case is so
idiosyncratic. Few studies have related synesthesia directly to brain function or brain
organization, and different people may experience synesthesia for different reasons.
Various hypotheses have been advanced to account for synesthesia, including:
extraordinary neural connections between the different sensory regions that are related
in a particular synesthetic person,
increased activity in areas of the frontal lobes that receive inputs from more than
one sensory area, and
unusual patterns of cerebral activation in response to particular sensory inputs.
Whatever the explanation, the brains of synesthetic people clearly think differently
about certain types of sensory inputs from the brains of other people.
INTELLIGENCE
Most people would probably say that one of the biggest influences on anyone’s thinking
ability is intelligence.We consider intelligence easy to identify in people, and even
easy to observe in other animals. Yet intelligence is not at all easy to define. Despite
years of studying human intelligence, researchers are not yet in agreement about what
intelligence entails. We therefore begin this section by reviewing some hypotheses of
intelligence.
The Concept of General Intelligence
In the 1920s, Charles Spearman proposed that, although there may be different kinds
of intelligence, there is also some sort of underlying general intelligence, which he
called the “g” factor. Consider for a moment what a general factor in intelligence might
mean for the brain. Presumably, brains with high or low “g” would have some general
difference in brain architecture.
This difference could not be something as simple as size, because human brain size
(which varies from about 1000 to 2000 grams) correlates poorly with intelligence. Another
possibility is that “g” is related to some special characteristic of cerebral connec-
In Review .
No two brains are alike, and no two people think the same. Nevertheless, although many
individual differences in brain structure and thinking are idiosyncratic, there are also systematic
variations, such as those related to sex and handedness. The reasons for these differences
in the cerebral organization of thinking are not known; they are undoubtedly
related to differences in the synaptic organization of the neural circuits that underlie different
types of cognitive processing.
558 ! CHAPTER 14
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tivity or even to the ratio of neurons to glia. Still another possibility
is that “g” is related to the activation of specific brain regions,
possibly in the frontal lobe (Duncan et al., 2000; Gray &
Thompson, 2004).
The results of preliminary studies of Albert Einstein’s brain
imply that cerebral connectivity and glia-to-neuron ratio may
play important roles. Sandra Witelson and her colleagues (Witelson,
Kigar, & Harvey, 1999) found that, although Einstein’s
brain was the same size and weight as the average male brain, the lateral fissure was
short in Einstein’s brain, as illustrated in Figure 14-20 (compare Figure 14-12), and
both the left and the right lateral fissures had a particularly striking upward deflection.
This arrangement essentially fuses the inferior parietal area with the posterior temporal
area.
The inferior parietal cortex is known to have a role in mathematical reasoning, and
so it is tempting to speculate that Einstein’s mathematical abilities were related to rearrangements
of this area. But there may be another important difference in Einstein’s
brain. Marion Diamond and her colleagues (1985) looked at the glia-to-neuron ratio
in Einstein’s brain versus the mean for a control population. They found that Einstein’s
inferior parietal cortex had a higher glia-to-neuron ratio than average, meaning that
each of his neurons in this region had an unusually high number of glial cells supporting
them.
The glia-to-neuron ratio was not unusually high in any other cortical areas of Einstein’s
brain measured by these researchers. Possibly, then, certain types of intelligence
could be related to differences in cell structure in localized regions of the brain. But,
even if this hypothesis proves to be correct, it still offers little neural evidence in favor
of a general factor in intelligence.
A neuropsychological possibility is that the “g” factor is related to language
processes in the brain. Recall that language ability qualitatively changes the nature of
cognitive processing in humans. So perhaps people with very good language skills also
have an advantage in general thinking ability.
Multiple Intelligences
There have been many other hypotheses of intelligence since Spearman’s, but few have
considered the brain directly. One exception is a proposal by Howard Gardner, a neuropsychologist
at Harvard. Gardner (1983) considered the effects of neurological injury
on people’s behavior.He concluded that there are seven distinctly different forms of intelligence
and that each form can be selectively damaged by brain injury. This view that
there are multiple kinds of human intelligence should not be surprising, given the many
different types of cognitive operations that the human brain is capable of performing.
Gardner’s seven categories of intelligence are: linguistic, musical, logical-mathematical,
spatial, bodily-kinesthetic, intrapersonal, and interpersonal. Linguistic and musical
intelligence are straightforward concepts, as is logical-mathematical intelligence.
Spatial intelligence refers to the spatial abilities discussed in this chapter, especially the
ability to navigate in space, and the ability to draw and paint. Bodily-kinesthetic intelligence
refers to superior motor abilities, such as those exemplified by skilled athletes and
dancers.
The two types of “personal” intelligence are less obvious. They refer to operations
of the frontal and temporal lobes that are required for success in a highly social environment.
The intrapersonal aspect is an awareness of one’s own feelings, whereas the
HOW DOES THE BRAIN THINK? ! 559
Figure 14-20
Einstein’s Brain The lateral fissure (at
arrows) takes an exaggerated upward
course relative to its course in typical
brains, essentially fusing the posterior
temporal regions with the inferior
parietal regions. Reprinted with the
permission of S. Witelson, D. Kigar, T. Harvey,
and The Lancet, June 19, 1999.
Associated Press
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extrapersonal aspect is the ability to recognize the feelings of others and to respond appropriately.
Gardner’s definition of intelligence has the advantage not only of being
quite inclusive but also of acknowledging forms of intelligence not typically recognized
in industrialized cultures.
One prediction stemming from Gardner’s analysis of intelligence is that brains
ought to differ in some way when people have more of one form of intelligence and
less of another. Logically, we could imagine that, if a person were higher in musical intelligence
and lower in interpersonal intelligence, then the regions of the brain for
music (especially the temporal lobe) would differ in some fundamental way from the
“less efficient” regions for interpersonal intelligence. Unfortunately, we do not know
what that difference might be.
Divergent and Convergent Intelligence
One of the clearest differences between lesions in the parietal and temporal lobes and
lesions in the frontal lobes is in the way in which they affect performance on standardized
intelligence tests. Posterior lesions produce reliable, and often large, decreases
in intelligence test scores, whereas frontal lesions do not. One thing is puzzling,
however. If frontal-lobe damage does not diminish a person’s score on an intelligence
test, why do people with this kind of damage often do such “stupid” things? The answer
lies in the difference between two kinds of intelligence referred to as divergent and
convergent.
According to J. P. Guilford (1967), traditional intelligence tests measure what is
called convergent thinking—that is, thinking that applies a person’s knowledge and
reasoning skills so as to narrow the range of possible solutions to a problem, zeroing
in on one correct answer. Typical intelligence test items using vocabulary words, arithmetic
problems, puzzles, block designs, and so forth, all require convergent thinking.
They demand a single correct answer that can be easily scored.
In contrast, divergent thinking reaches outward from conventional knowledge
and reasoning skills to explore new, more unconventional kinds of solutions to problems.
Divergent thinking assumes a variety of possible approaches and answers to a
question, rather than a single “correct” solution. A task that requires divergent thinking
is to list all the possible uses for a coat hanger that you can imagine. Clearly, a person
who is very good at divergent thinking might not necessarily be good at convergent
thinking, and vice versa.
The distinction between divergent and convergent intelligence is useful because it
helps us to understand the effects of brain injury on thought. Frontal-lobe injury is believed
to interfere with divergent thinking rather than with the convergent thinking
measured by standardized I.Q. tests. The convergent intelligence of people with damage
to the temporal and parietal lobes is often impaired.
Injury to the left parietal lobe, in particular, causes devastating impairment of the
ability to perform cognitive processes related to academic work. These people may be
aphasic, alexic, and apraxic. They often have severe deficits in arithmetic ability. All
such impairments would interfere with school performance or, in fact, performance at
most jobs.
Our patient M. M., discussed earlier, had left-parietal-lobe injury and was unable
to return to school. In contrast with people like M.M., those with frontal-lobe injuries
seldom have deficits in reading, writing, or arithmetic and show no decrement in standardized
I.Q. tests. C. C.’s case is a good example.
C. C. had a meningioma along the midline between the two frontal lobes; extracting
it required the removal of brain tissue from both hemispheres. C. C. had been a
560 ! CHAPTER 14
Convergent thinking. Form of thinking
that searches for a single answer to a
question (such as 2 ! 2 " ?); contrasts
with divergent thinking.
Divergent thinking. Form of thinking
that searches for multiple solutions to a
problem (such as, how many different
ways can a pen be used?); contrasts with
convergent thinking.
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prominent lawyer before his surgery; afterward, although he still had a superior I.Q.
and superior memory, he was unable to work, in part because he no longer had any
imagination. He could not generate the novel solutions to legal problems that had
characterized his career before the surgery. Thus, both M.M. and C. C. suffered problems
that prevented them from working, but their problems differed because different
kinds of thinking were affected.
Intelligence, Heredity, Environment, and
the Synapse
Another way of categorizing human intelligence was proposed by Donald Hebb. He,
too, thought of people as having two forms of intelligence, which he called intelligence
A and intelligence B. Intelligence A refers to innate intellectual potential, which is
highly heritable. That is, it has a strong genetic component. Intelligence B is observed
intelligence, which is influenced by experience as well as other factors, such as disease,
injury, or exposure to environmental toxins, especially in development.
Hebb understood that the structure of brain cells can be significantly influenced
by experience. In his view (Hebb, 1980), experiences influence brain development and
thus observed intelligence because they alter the brain’s synaptic organization. It follows
that people with lower-than-average intelligence A can raise their intelligence B
by appropriate postnatal experiences, whereas people with higher-than-average intelligence
A can be negatively affected by a poor environment. The task is to identify what
is a “good” and a “bad” environment in which to stimulate people to reach their highest
potential intelligence.
One implication of Hebb’s view of intelligence is that the synaptic organization of
the brain plays a key role. This synaptic organization is partly directed by a person’s
genes, but it is also influenced by experience. Variations in the kinds of experiences to
which people are exposed, coupled with variations in genetic patterns, undoubtedly
contribute to the individual differences in intelligence that we observe—both quantitative
differences (as measured by I.Q. tests) and qualitative differences (as in Gardner’s
view).
The effects of experience on intelligence may not be simply due to differences in
synaptic organization. Experience changes not only the number of synapses in the
brain but also the number of glia. Remember that Einstein’s brain was found to have
more glia per neuron in the inferior parietal cortex than control brains did. Intelligence,
then, may be influenced not only by the way in which synapses are organized
but also by glial density.
In Review .
Researchers have proposed many different forms of human intelligence, including Spearman’s
concept of general intelligence, Gardner’s idea of multiple intelligences, Guilford’s
concepts of convergent and divergent thinking, and Hebb’s intelligence A and intelligence
B. Each form of intelligence that humans possess is likely related to particular
structural organizations in the brain. To date, we know little about the structural differences
that account for the significant individual variations in intelligence that we observe.
Preliminary findings from studies of Einstein’s brain suggest some provocative
possibilities, however.
HOW DOES THE BRAIN THINK? ! 561
Intelligence A. Hebb’s term for innate
intellectual potential, which is highly
heritable and cannot be measured
directly.
Intelligence B. Hebb’s term for
observed intelligence, which is influenced
by experience as well as other factors in
the course of development and is
measured by intelligence tests.
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CONSCIOUSNESS
Conscious experience is familiar to all of us, yet it remains a largely mysterious product
of the brain.Everyone has an idea of what it means to be conscious, but, like thinking and
intelligence, consciousness is easier to identify than to define.Definitions range from the
view that consciousness is merely a manifestation of complex processes of thought to
more-slippery notions that see consciousness as being the subjective experience of
awareness or of “the inner self.”Despite the difficulty of saying exactly what consciousness
is, scientists generally agree that it is a process, not a thing. And consciousness is
probably not a single process but a collection of several processes, such as those associated
with seeing, talking, thinking, emotion, and so on. Recall that Descartes defined
consciousness as the ability to speak and to reason by using past memories (Chapter 1).
Consciousness is also not unitary but can take various forms. A person is not necessarily
equally conscious at all stages of life.We don’t think of a newborn baby as being
conscious in the same way that a healthy older child or adult is. Indeed, we might say
that part of the process of maturation is becoming fully conscious. Recall from Chapter
12 that the level of consciousness even changes across the span of a day as we pass
through various states of drowsiness, sleep, and waking. One trait that characterizes
consciousness, then, is its constant variability.
Why Are We Conscious?
Countless people, including neuroscience researchers, have wondered why we have the
experience that we call consciousness, which we define here as the level of responsiveness
of the mind to impressions made by the senses. The simplest explanation is that
we are conscious because it provides an adaptive advantage. Either our creation of the
sensory world or our selection of behavior is enhanced by being conscious. Consider
visual consciousness as an example.
According to Francis Crick and Christof Koch (1998), an animal such as a frog acts
a bit like a zombie when it responds to visual input. Frogs respond to small, preylike
objects by snapping and to large, looming objects by jumping. These responses are
controlled by different visual systems and are best thought of as being reflexive rather
than conscious. These visual systems work well for the frog. So why do we need to add
consciousness?
Crick and Koch suggested that reflexive systems are fine when the number of such
systems is limited, but, as their number grows, reflexive arrangements become inefficient,
especially when two or more systems are in conflict. As the amount of information
about an event increases, it becomes advantageous to produce a single, complex
representation and make it available for a sufficient time to the parts of the brain (such
as the frontal lobes) that make a choice among many possible plans of action. This sustained,
complex representation is consciousness.
We must still have the ability to respond quickly and unconsciously when we need
to. This ability exists alongside our ability to process information consciously. Recall
from the discussion of the visual system in Chapter 8 that the ventral stream is conscious,
but the dorsal stream, which acts more rapidly, is not. The action of the unconscious,
on-line dorsal stream can be seen in athletes. To hit a baseball or tennis ball
traveling at more than 100 miles per hour requires athletes to swing before they are
consciously aware of actually seeing the ball. The conscious awareness of the ball comes
just after hitting it.
In a series of experiments, Marc Jeannerod and his colleagues (Castiello, Paulignan,
& Jeannerod, 1991) found a similar dissociation between behavior and awareness
562 ! CHAPTER 14
Consciousness. Level of responsiveness
of the mind to impressions made by the
senses.
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in normal volunteers as they make grasping movements. Experiment 14-6 illustrates
the results of a representative experiment. Subjects were required to
grasp one of three rods as quickly as possible. The correct target rod on any
given trial was indicated by a light on that rod.
On some trials, unbeknown to the subjects, the light jumped from one target
to another. Subjects were asked to report if such a jump had occurred. As
shown in the Results section of the experiment, although subjects were able to
make the trajectory correction, they were sometimes actually grasping the correct
target before they were aware that the target had changed. On some trials,
there was a dissociation between motor and vocal responses such that, to their
surprise, subjects had already grasped the target some 300 ms before they emitted
the vocal response. Like baseball players, they experienced conscious awareness
of the stimulus event only after their movements had taken place. No
thought was required to make the movement, just as frogs catch flies without
having to think about it.
Such movements are different from those consciously directed toward a
specific object, as when we reach into a bowl of jellybeans to select a candy of a
certain color. In this case, we must be aware of all the different colors surrounding
the color that we want. Here the conscious ventral stream is needed
to discriminate among particular stimuli and respond differentially to them.
Consciousness, then, allows us to select behaviors that correspond to an understanding
of the nuances of sensory inputs.
What Is the Neural Basis of Consciousness?
Consciousness must be related in some way to the activity of neural systems in
the brain, particularly in the forebrain.One way to investigate these systems is to
contrast two kinds of neurological conditions. The first is the condition in which
a person lacks conscious awareness about some subset of information, even
though he or she processes that information unconsciously.
Examples include blindsight (see D. B.’s case in Chapter 8), form agnosia (see
D. F.’s case, also in Chapter 8), implicit learning in amnesia (discussed in Chapter
13), and visual neglect (discussed in this chapter). Another example is obsessivecompulsive
disorder, in which people persist in some behavior, such as checking to see
that the stove is off, even though they have already checked a great many times.
All these examples show that stimuli can be highly processed by the brain without
entering conscious awareness. These phenomena are quite different from the neurological
condition in which people experience conscious awareness of stimuli that are
not actually there. Examples include phantom limbs (discussed in Chapter 13) and the
hallucinations of schizophrenia. In both these cases, there is consciousness of specific
events, such as pain in a missing limb or the perception of voices, even though these
events are clearly not “real.”
Two conclusions can be drawn from these contrasting examples. First, the representation
of a visual object or event is likely to be distributed over many parts of the
visual system and probably over parts of the frontal lobes as well. Damage to different
areas not only produces different specific symptoms, such as agnosia or neglect, but
can also produce a specific loss of visual consciousness. Second, because visual consciousness
can be lost, it follows that parts of the neural circuit must produce this
awareness.
At the beginning of this chapter, we considered the idea that the unit of thinking
is the neuron. It is unlikely, however, that the neuron can be the unit of conscious
HOW DOES THE BRAIN THINK? ! 563
3
2
1
EXPERIMENT 14-6
Question: Can people alter their movements without
conscious awareness?
Procedure
Results
It is possible to dissociate behavior and
conscious awareness.
Conclusion
In this trial, the
subject reaches for
illuminated rod 3.
Subjects were
required to move
their hands and grasp
the illuminated rod
as quickly as possible.
3
2
1
On some trials, the
light jumps from one
target to another,…
… causing the
subject to correct his
trajectory. Most
subjects found that
they were actually
grasping the new
target before they
were aware that it
had moved.
Adapted from “The Neural Correlates of Conscious
Experience,” by C. Frith, R. Perry, and E. Lumer,
1999, Trends in Cognitive Sciences, 3, pp. 105–114.
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experience. Instead, consciousness is presumably a process that somehow emerges
from neural circuits, with greater degrees of consciousness being associated with increasingly
complex circuitry.
For this reason, humans, with their more complex brain circuits, are often suggested
to have a greater degree of consciousness than other animals do. Simple animals
such as worms are assumed to have less consciousness (if any) than dogs, which in turn
are assumed to have less consciousness than humans. Brain injury may alter self-awareness
in humans, as in contralateral neglect, but, unless a person is in a coma, he or she
still retains some conscious experience.
Some people have argued that language makes a fundamental change in the nature
of consciousness. Recall Gazzaniga’s belief that the left hemisphere, with its language
capabilities, is able to act as an interpreter of stimuli. This ability, he felt, is an
important difference between the functions of the two hemispheres. Yet people who
are aphasic are not considered to have lost consciousness. In short, although language
may alter the nature of our conscious experience, any one brain structure seems unlikely
to be equated with consciousness. Rather, viewing consciousness as a product
of all cortical areas, their connections, and their cognitive operations makes more
sense.
We end this chapter on an interesting, if speculative, note. David Chalmers (1995)
proposed that consciousness includes not only the information that the brain experiences
through its sensory systems but also the information that the brain has stored
and, presumably, the information that the brain can imagine. In his view, then, consciousness
is the end product of all the brain’s cognitive processes.
An interesting implication of such a notion is that, as the brain changes with experience,
so does the state of consciousness. As our sensory experiences become richer
and our store of information greater, our consciousness may become more complex.
From this perspective, there may indeed be some advantage to growing old.
SUMMARY
What is thinking? One of the products of brain activity in both humans and nonhumans
is the generation of complex processes that we refer to as thinking or cognition.
Various cognitive operations are described by English words such as language and
In Review .
In the course of human evolution, sensory experience has become increasingly complex
as the brain has expanded the analyses performed by sensory systems. It is hypothesized
that this informational complexity must be organized in some fashion and that consciousness
is a property of the nervous system that emerges as a result. Viewed in this
way, consciousness allows the brain to produce a single representation of experience at
any given moment and to make a choice among the many different and sometimes conflicting
possible plans of action. As relative human brain size has increased in our evolution,
so, too, has our degree of consciousness. But not all behavior needs to be
controlled consciously. In fact, it is better that we are able to make rapid movements,
such as batting a ball, without conscious thought. In such cases, speed is critical, and it
would be impossible to respond quickly enough if there were conscious analysis of the
movements.
564 ! CHAPTER 14
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memory. These operations, however, are not physical things, but rather psychological
constructs. They are merely inferred and are not to be found in discrete places in the
brain. The brain carries out multiple cognitive operations including perception, action
for perception, imagery, planning, spatial cognition, and attention. These operations
require the widespread activity of many cortical areas.
What is the neural basis of cognition? The unit of cognition is the neuron. Neurons
in the association cortex specifically take part in most forms of cognition.Various syndromes
result from association-cortex injury, including agnosia, apraxia, aphasia, and
amnesia. Each syndrome includes the loss or disturbance of a form of cognition.
What is cerebral asymmetry? The cognitive operations of the brain are organized
asymmetrically in the cerebral hemispheres, with the two hemispheres carrying out
complementary functions. The most obvious functional difference in the two hemispheres
is language, which is normally housed in the left hemisphere. Cerebral asymmetry
is manifested in anatomical differences between the two hemispheres and can be
inferred from the differential effects of injury to opposite sides of the brain. Asymmetry
can also be seen in the normal brain and in the brain that is surgically split for the
relief of intractable epilepsy.
What might account for individual differences in cognition? Unique brains produce
unique thought patterns. Marked variations in brain organization exist among individual
people, as exhibited by idiosyncratic differences such as synesthesia. Systematic
differences exist as well, as in the performance of females and males on various cognitive
tests, especially on tests of spatial and verbal behavior. Sex differences result
from the action of gonadal hormones on the organization of the cerebral cortex, possibly
on the formation of the architecture of cortical neurons. Not only is the action
of the hormones important but also the timing of those actions. Differences also appear
in the organization of the cerebral hemispheres in right- and left-handers. Rather
than being a single group, however, left-handers constitute at least three different
groups: one whose members appear to have speech in the left hemisphere, as righthanders
do, and two that have anomalous speech representation, either in the right
hemisphere or in both hemispheres. The reason for these organizational differences
remains unknown.
What is the neural basis of intelligence? Intelligence is difficult to define. In fact,
we find various forms of intelligence among humans within our own culture and in
other cultures. There are obvious differences in intelligence across species, as well as
within a species. Intelligence is not related to differences in brain size within a species
or to any obvious gross structural differences between different members of the species.
It may be related to differences in synaptic organization or to the ratio of glia to
neurons.
What methods are used to study how the brain thinks? Neuropsychological studies,
which began in the late 1800s, examine the behavioral capacities of people and laboratory
animals with localized brain injuries. The development of different types of
brain-recording systems, such as EEG, ERP, and MEG, has led to new ways of measuring
brain activity while subjects are engaged in various cognitive tasks. Brain metabolism
can also be measured by using imaging techniques such as PET and fMRI. An
alternative to correlating metabolic activity with behavior is to stimulate the brain
during cognitive activity, a technique that disrupts behavior. The original studies by
Penfield used direct electrical stimulation, but more recently transcranial magnetic
stimulation has been used to disrupt activity. With the use of multiple methods, it is
possible to gather converging evidence on the way in which the brain thinks.
HOW DOES THE BRAIN THINK? ! 565
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What is consciousness, and how does it relate to brain organization? The larger a
species’ brain is relative to its body size, the more knowledge the brain creates. Consciousness
is a property that emerges from the complexity of the nervous system.
KEY TERMS
REVIEW QUESTIONS
1. What are the characteristics of thinking? How do these characteristics relate to
the brain?
2. Summarize the role of the association cortex in thinking.
3. In what ways is the function of the cerebral hemispheres asymmetrical? In what
ways is its functioning symmetrical?
4. Identify the key variations in cerebral asymmetry.
5. How does intelligence relate to brain organization?
FOR FURTHER THOUGHT
1. Contrast the ideas of syntax, mirror neurons, and the integrative mind with
respect to the neural control of thinking.
2. What types of studies are necessary to identify a neural basis of consciousness?
RECOMMENDED READING
Barlow, H. (1995). The neuron doctrine in perception. In M. Gazzaniga (Ed.), The cognitive
neurosciences (pp. 415–435). Cambridge, MA: MIT Press. Barlow introduces the reader
to the fascinating question of what the basic neural unit of cognition might be. He
traces the history of thinking about the problem and provides a nice summary of the
evidence that the neuron is the basic unit of cognition.
Calvin,W. H. (1996).How brains think. New York: Basic Books. This delightful book ties
together information from anthropology, evolutionary biology, linguistics, and the
neurosciences to deliver an entertaining account of how intelligence evolved and how it
may work. This little book would be a wonderful springboard for a group discussion at
the undergraduate level and beyond.
Cytowic, R. E. (1998). The man who tasted shapes. Cambridge, MA: MIT Press. Cytowic
gives us an inside look at the cases that led him to study synesthesia. Reading about
anomalous speech
representation, p. 555
association cortex, p. 527
attention, p. 530
cell assembly, p. 522
cognition, p. 523
cognitive neuroscience,
p. 536
consciousness, p. 562
contralateral neglect,
p. 532
convergent thinking, p. 560
dichotic listening, p. 545
divergent thinking, p. 560
extinction, p. 532
functional magnetic
resonance imaging
(fMRI), p. 539
intelligence A, p. 561
intelligence B, p. 561
magnetic resonance
imaging (MRI), p. 539
magnetoencephalography
(MEG), p. 539
mirror neuron, p. 535
neuropsychology, p. 536
psychological construct,
p. 522
split brain, p. 546
synesthesia, p. 555
syntax, p. 523
transcranial magnetic
stimulation (TMS),
p. 539
566 ! CHAPTER 14
neuroscience interact ive
Many resources are available for
expanding your learning on line:
www.worthpublishers.com/kolb/
chapter14
Try some self-tests to reinforce your
mastery of the material. Look at some
of the updates on current research.
You’ll also be able to link to other sites
that will reinforce what you’ve learned.
www.apraxia-kids.org
Learn more about apraxia and how it
affects children from this Web site from
the headquarters of the Childhood
Apraxia of Speech Association.
www.web.mit.edu/synesthesia/
www/synesthesia.html
Work through some interactive
demonstrations of what it might be like
to have synesthesia at this Web site
from the Massachusetts Institute of
Technology.
On your CD-ROM, you can review the
brain anatomy that underlies cognition
in the module on the Central Nervous
System.
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“pointed tastes” is better than science fiction, especially for the majority of us who can
barely imagine such sensory experiences.
Kimura, D. (1999). Sex and cognition. Cambridge, MA: MIT Press. Kimura has written a
short yet comprehensive monograph on what is known about sex differences in brain
organization and function. She is critical but fair in her analysis of the literature. The
book is nicely spiced with ideas about what sex differences in brain organization might
mean.
Kolb, B., & Whishaw, I. Q. (2003). Fundamentals of human neuropsychology (5th ed.). New
York:Worth Publishers. For those who want to read more about the organization of the
human brain and the ways in which brain injury alters cognition, this book provides a
broad introduction. Indeed, the authors, who incidentally are the authors of the book
that you are reading, also provide more extensive discussions of the material that you
read in Chapters 8 through 11, 13, and 14.
HOW DOES THE BRAIN THINK? ! 567
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Focus on New Research: Neuropsychoanalysis
Research on Brain and
Behavioral Disorders
Multidisciplinary Research Methods
Causes of Abnormal Behavior
Investigating the Neurobiology of Behavior Disorders
Classifying and Treating Brain and
Behavioral Disorders
Identifying and Classifying Mental Disorders
Treatments for Disorders
Focus on New Research: Treating Behavioral
Disorders with TMS
Understanding and Treating
Neurological Disorders
Traumatic Brain Injury
Stroke
Epilepsy
Multiple Sclerosis
Neurodegenerative Disorders
Are Parkinson’s and Alzheimer’s Aspects of
One Disease?
Understanding and Treating
Psychiatric Disorders
Psychotic Disorders
Mood Disorders
Focus on New Research: Antidepressant Action
in Neurogenesis
Anxiety Disorders
Is Misbehavior Always Bad?
568 !
C H A P T E R 15
What Happens When the
Brain Misbehaves?
Left: Dr. Dennis Kunkel/Phototake. Middle: Randy Faris/CORBIS.
Right: ISM/Phototake.
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discipline of neuroscience. But, as neurobehavioral studies
became more sophisticated, it became clear that people do
engage in a lot of unconscious processing. Recall the evidence
that we are largely unaware of our dorsal visual
stream (Chapter 8) or the operations of the systems underlying
implicit memory (Chapter 13).
What about repressing unpalatable thoughts or behaviors?
People with contralateral neglect deny that they have
any problems (Chapter 14). A woman with contralateral
neglect is beautifully illustrated in a case described by
Vilayanur Ramachandran (1995). He irrigated her left ear
canal with cold water.
The technique temporarily stimulates the vestibular
system and removes the neglect. The woman suddenly became
aware of her paralyzed arm and knew that it had
been paralyzed continuously since her stroke 8 days earlier.
She was thus capable of recognizing both her deficit
and that she had unconsciously registered the deficit.
Remarkably, when the stimulation wore off, the woman
once again showed neglect. She reverted to the belief that
her arm was normal. She was even unable to recall that she
Neuropsychoanalysis
Focus on New Research
I dentifying the neural basis of
brain disorders and abnormal
behavior has suffered from the lack
of a unifying theory. Among the
questions that a unifying theory of
neuropsychology would answer is,
How does the brain produce our
concept of self, our beliefs about
who we are as individuals?
The first coherent attempt at a
theory of self is found in the writings
of Sigmund Freud and other psychiatrists, beginning a
century ago. Freud’s theories were based on his observations
of his patients and were made without the help of the
anatomical or imaging data available today. The underlying
tenet of Freud’s theory is that our motivations remain largely
hidden in our unconscious minds.
Freud posited that these motivations, largely our sexual
and aggressive urges, are actively withheld from conscious
awareness by a mysterious repressive force. He believed
that mental illness results from the failure of repressive
processes. Freud proposed three components of mind, illustrated
in Figure 15-1A:
1. Primitive functions, including “instinctual drives” such
as sex and aggression, are located in the part of the
mind that Freud thought to be operating on an unconscious
level and called the id.
2. The rational part of the mind he called the ego. Much
of the activity of the ego Freud also believed is unconscious,
although experience (to him, our perceptions of
the world) is conscious.
3. The superego aspect of mind acts to repress the id and
to mediate the ongoing interaction between the ego
and the id.
For Freudians, abnormal behaviors result from the emergence
of unconscious drives into voluntary, conscious
behavior. The aim of psychoanalysis, the original talking
therapy, is to trace the symptoms back to their unconscious
roots and thus expose them to rational judgment.
By the 1960s, the notion of id-ego-superego seemed
antiquated and without much relevance to the emerging
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Figure 15-1
Mind Models (A) Freud based his model of the mind, drawn
in 1933, solely on clinical observations (color added). Dotted
lines mark the border between conscious and unconscious
processing. (B) Contemporary brain-imaging and lesioning
studies map a “mind” model comparable to the one developed
by Freud. The brainstem and limbic system correlate with
Freud’s depiction of the id, the ventral frontal and posterior
cortex with the ego, and the dorsal frontal cortex with the
superego. Part A from A. W. Freud et al., by arrangement with Paterson
Marsh Ltd, London; coloring added by Oliver Turnbull. Part B adapted from a
drawing by Oliver Turnbull.
Dorsal frontal
cortex is locus
of self-conscious
thought.
ID
EGO
unconscious
preconscious
Ventral frontal
cortex regulates
inhibitions. Limbic system and
brainstem regulate
instincts and drives.
Posterior cortex
generates sensory
representations
of the world.
(A) (B)
S U P E R E G O
repressed
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tions of who they are, and, though our behavior is hardly
driven by “sex,” sexual and other pleasurable behaviors play
a major role in everyday life. Recall that the neurotransmitter
dopamine has been associated with seeking pleasurable
rewards such as drugs, sexual activity, and food.
Dopamine could certainly fit into Freud’s model of
the mind. Similarly, the behavior of frontal-lobe patients
(Chapter 11) is what one might expect from a damaged mind
in which inhibitory (repressive) functions are impaired. Such
people may act impulsively and seemingly without concern
for the social consequences of their actions. Recall from
Chapter 13 that people with psychogenic amnesia have
drastically reduced metabolic activity in the frontal lobe.
Figure 15-1B is Solms’s simple model of how brain activity
could be related to Freud’s model. We do not wish to
push the Freudian perspective too far, and certainly debate
about its merit continues among neuroscientists, but we
want to introduce you to these ideas. In the final analysis,
understanding abnormal behavior will require some unified
theory of how the brain produces the mind, and a reinvention
of Freudian theory in a modern context provides an
example of how such a model might operate.
had acknowledged that the arm was abnormal, even though
she could recall most other details of what had happened
during the cold-water therapy.
It was obvious to Ramachandran that memories can be
selectively repressed. Patients rationalize away unwanted
facts, a behavior also described in Chapter 14 with patients
given sodium amytal. Such patients experience a period
of aphasia and hemiparalysis yet deny that they had any
difficulties during the drug administration. Mark Solms
(2004) thus wondered if repression, the cornerstone of
Freud’s theories, might indeed be a central feature of the
normal human mind.
But what is being repressed normally? Remember that
the organization of the human brain is not much different
from that of other primates or even from mammals more
generally. If you have pets (or if you have read Chapter 11),
you know that much of what seems to drive animal behavior
is directed toward pleasurable reward, whether it is attention
or food from their owners or the chance to hunt or
chase a Frisbee.
Freud argued that human behavior is similarly governed
by the pleasure principle. People cling to false no-
570 ! CHAPTER 15
Investigating the origins and treatment of abnormal behavior is perhaps the most
fascinating pursuit in the study of the brain and behavior.We have explored brain
systems and encountered brain disorders throughout this book. Our task now is
synthesis, to consider the neural basis of behavioral disorders systematically, in regard
to research, diagnosis, and treatment strategies.
Consider first the established distinction between the diagnosis and the treatment
of “neurological” and “psychiatric” disorders. Once a single discipline, today neurological
and psychiatric disorders tend to be treated by two different medical specialists:
neurologists and psychiatrists. Neurologists identify and treat brain pathology medically.
Since Freud, in contrast, psychiatrists have embraced psychoanalysis along with
their medical training. Psychiatrists treat patients with pharmacological and other
medical treatments in combination with behavioral therapies, and clinicians offer behavioral
treatments ranging from counseling to psychotherapy.
Neurology and psychiatry became quite separate in the twentieth century. But, as
researchers learn more about the neurological basis of psychiatric disorders, the disciplines
are growing more similar once again. At present, however, neurologists treat
organic disorders of the nervous system such as Parkinson’s disease and stroke. Psychiatrists
treat behavioral disorders such as schizophrenia and depression.
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With the organic-neurological and behavioral-psychiatric distinction in mind, we
look next at how researchers investigate the neurobiology of organic and psychiatric disorders.
We then examine how disorders are classified and distributed in the population.
After surveying general treatment categories, we review established and emerging treatments
for representative disorders that you have encountered throughout the book.
RESEARCH ON BRAIN AND BEHAVIORAL DISORDERS
The rich history and multidisciplinary nature of neuroscience research makes studying
and understanding the brain relevant to all fields of human endeavor and no less
relevant to our own personal understanding of our selves.
Multidisciplinary Research Methods
From the ideas of Aristotle in antiquity to Descartes and to
Darwin presented in Chapter 1, you have seen how fields as diverse
as philosophy, biology, and even robotics shape our contemporary
view of the brain. In the century and a half since
Darwin articulated the biological foundation for the study of
the brain, brain research has become still more multidisciplinary,
ranging from clinical observation to the tools of molecular
biology and quantum physics.
One way to summarize the methods of studying the link
between brain and behavior is to consider them from the macro
level of the whole organism down to the molecular level, as
shown in Table 15-1. Behavioral studies by their very nature
are investigations of the whole organism. Those conducted by
Broca and others nearly 150 years ago, in which they examined
the relation between language disorders and brain damage,
were in many ways the starting point of systematic studies of
brain–behavior relations.
Later, behavioral studies used groups of patients or laboratory
animals with brain injuries. In the development of the
modern science of behavioral analysis since the 1950s, more
elaborate measures have been used both to analyze mental
activity and to relate behavior to brain states in intact, active
animals and humans. The emergence of molecular biology
through the 1990s and continuing today has enabled neuroscientists
to breed strains of animals, usually mice, with either a
gene knocked out (deleted or inactivated) or a gene inserted.
Today, neuroscientists are using knockout technology both
to create animal models of human disorders and to generate
treatments for neurobehavioral disorders (Chapter 3).
Improvements in brain-imaging techniques in the past
decade have made it possible for changes in brain activity to be
measured without direct access to the brain. Recall, for example,
the dissociation of linguistic and musical abilities both between
and within hemispheres that we examined in Chapter 9,
where we analyzed the procedures used in producing and interpreting
PET scans.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 571
Summary of Methods of Studying Brain
and Behavior
Chapter in which
an example
Technique is discussed
Behavioral studies
Clinical investigations of individual cases 11, 15
Neurosurgical studies of patients at surgery 9
Neuropsychological analyses of groups of patients 14
Neuropsychological analyses of laboratory animals 13
Ethological studies of behavior 6
Cognitive psychology and psychophysics 14
Developmental studies 7
Behavioral genetics 6
Brain imaging
Positron emission tomography (PET) 8
Functional magnetic resonance Imaging (fMRI) 14
Magnetic resonance spectroscopy (MRS) 15
Brain stimulation
Electrical stimulation 10
Transcranial magnetic stimulation (TMS) 14
Brain recording
Electroencephalography 5
Magnetoencephalography 14
Event-related potentials 5
Long-term enhancement 5
Single-cell recording 4
Brain anatomy
Cytological measures (i.e., measuring cell
morphology) 3
Histological measures (i.e., measuring cell
characteristics) 3
Tracing neural connections 4
Synaptic measures 13
Clinical investigations 15
Table 15-1
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Causes of Abnormal Behavior
Neuroscientists presume that abnormal behavior can result from abnormal brain functioning.
Evidence for brain abnormalities is relatively straightforward in neurological
disorders, and the causes are largely known, at least in a general sense:
1. genetic errors, as in Huntington’s disease
2. progressive cell death resulting from a variety of neurodegenerative causes, as in
Parkinson’s or Alzheimer’s disease
3. rapid cell death, such as in stroke or traumatic brain injury
4. loss of neural connections seen in disorders such as multiple sclerosis
In contrast with neurological disorders, far less is known about the causes of psychiatric
disorders. To date, no large-scale neurobiological studies have been done of
either postmortem pathology or biochemical pathology in the population at large. Still,
clues to possible causes of psychiatric behaviors have been uncovered throughout the
preceding chapters. In each case, some abnormality of the brain’s structure or activity
must be implicated. The questions asked by neuropsychologists are,What is that particular
brain abnormality? What is its cause?
Table 15-2 lists the most likely categories of causes underlying behavioral disorders,
micro to macro. At the microscopic level of causes is genetic error, such as that
responsible for Tay-Sachs disease. Genetic error is probably linked to some of the other
proposed causes, such as hormonal or developmental anomalies, as well.
Genes may be the source not only of anatomical, chemical, or physiological defects
but also of susceptibility to other factors that may cause behavioral problems. A person
may have a genetic predisposition to be vulnerable to stress, infection, or pollution,
which is the immediate cause of some abnormal conditions listed in Table 15-2. In
other cases, no genetic predisposition is needed, and abnormal behavior arises strictly
from environmental factors.
The triggering environmental factor may be poor nutrition or exposure to toxic
substances, including naturally occurring toxins, manufactured chemicals, and infectious
agents.Other disorders are undoubtedly related to negative experiences.Negative
experience ranges from developmental deprivation, the extreme psychosocial neglect
572 ! CHAPTER 15
Causes of Certain Behavioral Disorders
Cause Disorder (chapter discussed)
Genetic error Tay-Sachs disease (3)
Hormonal anomaly Androgenital syndrome (11)
Developmental anomaly Schizophrenia (7)
Infection Encephalitis (2)
Injury Traumatic brain injury (1)
Natural environmental toxins Shellfish poisoning (7)
Manufactured toxins MPTP poisoning (5)
Poor nutrition Korsakoff’s syndrome (13)
Stress Anxiety disorders (11)
Negative experience Developmental delays among Romanian orphans (6)
Table 15-2
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of Romanian orphans in the 1980s and 1990s detailed in Chapter 6 being one example,
to traumas or chronic stress in later life, such as experiences implicated in anxiety
disorders.
Investigating the Neurobiology
of Behavioral Disorders
That a single brain abnormality can cause a behavioral disorder, explaining everything
about that disorder and its treatment, is well illustrated. A defect in the gene for
phenylalanine hydroxylase, an enzyme that breaks down phenylalanine, causes
phenylketonuria (PKU). Babies with PKU have elevated levels of the amino acid
phenylalanine in their blood.
Left untreated, PKU causes severe mental retardation, but PKU can be easily
treated, just by restricting the dietary intake of phenylalanine. If other behavioral
disorders were as simple and well understood as PKU is, research in neuroscience
could quickly yield cures for them. Many disorders do not result from a
single genetic abnormality, however, and the causes of most disorders are still largely
conjectural.
The major problem is that a psychiatric diagnosis of developmental disability is
based mainly on behavioral symptoms, and behavioral symptoms give few clues to
specific neurochemical or neurostructural causes. This problem also can be seen in
treating PKU. Table 15-3 lists what is known about PKU at different levels of analysis:
genetic, biochemical, histological, neurological, behavioral, and social.
The underlying problem in PKU becomes less apparent with the procession of
entries in the table. In fact, it is not possible to predict the specific biochemical abnormality
from information at the neurological, behavioral, or social levels. But the
primary information available is at the neurological, behavioral, and social levels.
For most psychiatric diseases, the underlying pathology is unknown. For PKU, elevated
phenylpyruric acid levels in the urine of a single patient was the organic clue
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 573
Phenylketonuria: A Behavioral Disorder for Which the
Neurobiological Pathogenesis Is Known
Level of analysis Information known
Genetic Inborn error of metabolism; autosomal recessive defective gene
Biochemical pathogenesis Impairment in the hydroxylation of phenylalanine to tyrosine,
causing elevated blood levels of phenylalanine and its
metabolites
Histological abnormality Decreased neuron size and dendritic length, and lowered spine
density; abnormal cortical lamination
Neurological findings Severe mental retardation, slow growth, abnormal EEG
Behavioral symptoms For 95 percent of patients, IQ below 50
Social disability Loss of meaningful, productive life; significant social and
economic cost
Treatment Restrict dietary intake of phenylalanine
Source: Adapted from “Special Challenges in the Investigation of the Neurobiology of Mental Illness,” by G. R.
Heninger, 1999, in The Neurobiology of Mental Illness (p. 90), edited by D. S. Charney, E. J. Nestler, and B. S. Bunney,
New York: Oxford University Press.
Table 15-3
Phenylketonuria (PKU). Behavioral
disorder caused by elevated levels of the
amino acid phenylalanine in the blood
and resulting from a defect in the gene for
the enzyme phenylalanine hydroxylase;
the major symptom is severe mental
retardation.
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needed to understand the behavioral disorder. The task for future study and treatment
of most behavioral disorders is to identify the biological markers that will lead to similar
understandings.
CHALLENGES TO DIAGNOSIS
Knowledge about behavioral disorders is also hampered by its very nature.Most diagnostic
information gathered is about a patient’s behavior, which comes both from patients
and from their families. Unfortunately, people are seldom objective observers of
their own behavior or that of a loved one.We tend to be selective in noticing and reporting
symptoms. If we believe that someone has a memory problem, for example, we
often notice memory lapses that we might ordinarily ignore.
Furthermore, we are often not specific in identifying symptoms. Simply identifying
a memory problem is not really helpful. Treatment requires knowing exactly what
type of memory deficit is the basis of the problem. Loss of memory for words, places,
or habits implies very different underlying pathologies and brain systems.
Not only do patients and their loved ones make diagnosis difficult, but those who
do the diagnosing do so as well. Behavioral information about patients may be interpreted
by general physicians, psychiatrists, neurologists, psychologists, or social workers,
as well as by others. Evaluators with different conceptual biases shape and filter the
questions that they ask and the information that they gather differently.
One evaluator believes that most behavioral disorders are genetic in origin, another
believes that most result from a virus, and a third believes that many can be
traced to repressed sexual experiences during childhood. Each makes quite different
types of observations and gives very different kinds of diagnostic tests. In contrast, the
diagnosis of nonbehavioral disorders is not so dependent on subjective observations
made by an evaluator but rather depends on experimental methods.
RESEARCH CHALLENGES
Even if the problems of psychaitric diagnosis were solved, major obstacles to investigating
behavioral disorders would still exist. For organizational complexity, the nervous
system far outstrips other body systems. The brain has a wider variety of cell types
than does any other organ, and the complex connections among neurons add a whole
new dimension to understanding normal and abnormal functioning.
As our understanding of brain and behavior has progressed, it has become apparent
that multiple receptor systems serve many different functions. As George
Heninger (1999) pointed out, there is as yet no clear demonstration of a single receptor
system with a specific relation to a specific behavior. For example, the neurotransmitter
GABA (Chapter 7) affects some 30 percent of the synapses
in the brain. When GABA agonists such as benzodiazepines are
given to people, multiple effects on behavior become apparent. It
is difficult to administer enough of a benzodiazepine to reduce anxiety
to a “normal” level without producing sedative side effects as
well.
Other receptor systems detailed in Chapter 5, such as those involving
acetylcholine, dopamine, and serotonin, are equally diffuse,
with little specificity between biochemistry and behavior. One example
of a close relation between a receptor system and behavior
is seen in the dopaminergic system and its relation to Parkinson’s
disease. But even here it is impossible to tie dopamine depletion to a consistent behavioral
syndrome. Two people with Parkinson’s disease can have quite different
symptoms even though the basis of the disease is known to be a loss of neurons in the
substantia nigra.
574 ! CHAPTER 15
Frontal
cortex
Caudate nucleus
Corpus
callosum
Substantia nigra Cerebellum
Dopaminergic system
Active in maintaining
normal motor behavior.
Loss of dopamine is
related to Parkinson’s
disease, in which muscles
are rigid and movements
are difficult to make.
Increases in dopamine
activity may be related to
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Even if a patient has actual neuropathology, such as lesions in the nervous system,
determining the cause of a behavioral disorder may still be difficult. Magnetic resonance
imaging may show that a person with multiple sclerosis has many nervous system
lesions, yet the person displays very few outward symptoms. Similarly, only when
the loss of dopamine neurons exceeds about 60 to 80 percent do investigators see clinical
signs of Parkinson’s disease.
This is not to suggest that most of our brain cells are not needed. It simply shows
that the brain is capable of considerable plasticity.When diseases progress slowly, the
brain has a remarkable capacity for adapting.
Just as obvious brain lesions do not always produce behavioral symptoms, behavioral
symptoms are not always linked to obvious neuropathology. For instance, some
people have notable behavioral problems after suffering brain trauma, yet no obvious
signs of brain damage appear on an MRI scan. The pathology may be subtle, such as a
drop in dendritic-spine density, or so diffuse that it is hard to identify.
Given the current diagnostic methods for both behavioral disorders and neuropathology,
identifying disorders and their causes is seldom an easy task. A major avenue
for investigating the causes of behavioral disorders is to develop and study animal
models. For example, rats with specific lesions of the nigrostriatal dopamine system are
used as a model of Parkinson’s disease. This model has led to significant advances in
our understanding of how specific dopaminergic agonists and cholinergic antagonists
act in the treatment of Parkinsonism.
One problem with the use of animal models, however, is the oversimplified view
that they provide of the neurobiology of behavioral abnormalities. The fact that a drug
reduces symptoms does not necessarily mean that it is acting on a key biochemical aspect
of the pathology. Aspirin can get rid of a headache, but that does not mean that
the headache is caused by the receptors on which aspirin acts.
Similarly, antipsychotic drugs block D-2 receptors, but that does not mean that
schizophrenia is caused by abnormal D-2 receptors. It quite possibly results from a disturbance
in glutamatergic systems, and, for some reason, dopamine antagonists are effective
in rectifying the abnormality.
This is not to imply that animal models are unimportant.We have seen throughout
this book that they are important. But modeling human disorders is a complex
task, and so caution is needed when you read news stories about studies using animal
models that point toward possible cures for human behavioral diseases.
Such caution especially applies to psychiatric disorders in which causes are still unknown.
Furthermore, many symptoms of disorders such as schizophrenia and anxiety
are largely cognitive. The objective identification of any cognitive processes mimicked
by a laboratory model is difficult.
In Review .
Neurobiological investigations of behavioral disorders are based on the assumption that a
direct link ought to exist between brain abnormalities and disorders in behavior. In most
cases, however, this relation is far from direct. Discrete biological markers are difficult to
identify, except in the most well studied disorders. Surprisingly, we encounter instances of
brain pathology without obvious clinical symptoms and of clinical symptoms without obvious
pathology. Still, the general causes of behavioral disorders range from genetic factors
to negative experiences, including injuries, toxins, and stress. It will be some time,
however, before a science of brain and behavior can fully explain the disordered mind.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 575
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576 ! CHAPTER 15
CLASSIFYING AND TREATING BRAIN AND
BEHAVIORAL DISORDERS
Behavioral disorders afflict millions every year. Figure 15-2 summarizes the lifetime
rates of psychiatric disorders among people in the United States of America. Nearly
one-half of the sample had met the criteria for a psychiatric disorder at some point in
their lives. Of these people, only a minority had received treatment of any kind, and
an even smaller percentage had received treatment from a mental-health specialist.
Large-scale surveys of neurological disorders show a similar pattern of prevalence,
as summarized in Table 15-4. Acute disorders happen suddenly. Many of those
afflicted do not survive. They are represented in “short term” statistics. Statistics for
chronic disorders represent the survivors, people who have a disorder for a prolonged
period.
If you are surprised to find hearing disorders among the neurological, remember
that many disorders of hearing are related to a deficit either in the transduction of
sound into neural activity or in the eighth cranial nerve itself. Looking at the statistics
presented in Figure 15-2 and Table 15-4, we can only marvel that most people are relatively
normal most of the time.
Lifetime prevalence rate (%)
Anxiety
disorders
Agoraphobia
Generalized
anxiety
Panic
disorder
Mood
disorders
Major
depression
Mania
Substance
dependence
Alcohol
Other
drugs
Any
disorder
Psychosis
Social
phobia
KEY
Percentage of men who will have this disorder in
their lifetimes
Percentage of women who will have this disorder
in their lifetimes
Percentage of the total population who will have
this disorder in their lifetimes
0 10 20 30 40 50
Figure 15-2
Distribution of Psychiatric Disorders in
the United States Adapted from
“Lifetime and 12-Month Prevalence of DSM-III-R
Psychiatric Disorders in the United States,” by R.
C. Kessler, K. A. McGonagle, S. Zhao, D. B. Nelson,
M. Hughes, S. Eshleman, H. Wittchen, and K. S.
Kendler, 1994, Archives of General Psychiatry, 51,
pp. 8–19.
Prevalence of Major Neurological and
Communicative Disorders in the United States
Estimated
Disorder number of cases
Acute disorders (per year)
Trauma: head and spinal cord 500,000/yr
Stroke 500,000/yr
Infectious disorders 25,000/yr
TOTAL ACUTE 1,025,000/yr
Chronic disorders (cumulative survivors)
Nervous system
Stroke 2,000,000!
Traumatic brain injury 10,000,000!
Spinal-cord injury 500,000
Epilepsy 2,000,000
Hearing and speech
Deafness 2,000,000
Partial deafness 11,600,000
Speech 8,400,000
Language 6,600,000
Movement disorders (e.g., Parkinson’s,
Huntington’s, Tourette’s) 800,000
Demyelinating diseases (MS, ALS) 200,000
Disorders of early life (e.g., cerebral palsy) 1,000,000
Neuromuscular disorders 1,000,000
Other neurological disorders (e.g., chronic
pain, insomnia, neuro-AIDS) 9,000,000
TOTAL CHRONIC 55,100,000!
Table 15-4
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WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 577
Identifying and Classifying Mental Disorders
Epidemiology is the study of the distribution and causes of diseases in human populations.
A major contribution of epidemiological studies has been to help define and assess
behavioral disorders, especially those that we are labeling as psychiatric disorders.
The first set of criteria for diagnoses in psychiatry was developed in 1972. Since
that time, two parallel sets of criteria have been developed. One is the World Health
Organization’s International Classification of Diseases (ICD-10 being the most recent
version), and the other is the most recent edition of the American Psychiatric Association’s
Diagnostic and Statistical Manual of Mental Disorders, the DSM-IV, published
in 1994. In 2000, the APA revised the text to include research information developed
since publication in 1994. The classification scheme used in this most recent revision,
DSM-IV-TR, is summarized in Table 15-5.
Summary of DSM-IV-TR Classification of Abnormal Behaviors
Diagnostic category Core features and examples of specific disorders
Tend to emerge and sometimes dissipate before adult life: pervasive developmental disorders (such as
autism), learning disorders, attention-deficit hyperactivity disorder, conduct disorder, separation-anxiety
disorder
Dominated by impairment in cognitive functioning: Alzheimer’s disease, Huntington’s disease
Caused primarily by a general medical disorder: mood disorder due to a general medical condition
Substance-related disorders Brought about by the use of substances that affect the central nervous system: alcohol-use disorders,
opioid-use disorders, amphetamine-use disorders, cocaine-use disorders, hallucinogen-use disorders
Functioning deterioriates toward a state of psychosis, or loss of contact with reality
Mood disorders Severe disturbances of mood resulting in extreme and inappropriate sadness or elation for extended
periods of time: major depressive disorder, bipolar disorders
Anxiety disorders Anxiety: generalized anxiety disorder, phobias, panic disorder, obsessive-compulsive disorder, acute
stress disorder, posttraumatic stress disorder
Somatoform disorders Physical symptoms that are apparently caused primarily by psychological rather than physiological
factors: conversion disorder, somatization disorder, hypochondriasis
Fictitious disorders Intentional production or feigning of physical or psychological symptoms
Dissociative disorders Significant changes in consciousness, memory, identity, or perception, without a clear physical cause:
dissociative amnesia, dissociative fugue, dissociative identity disorder (multiple personality disorder)
Eating disorders Abnormal patterns of eating that significantly impair functioning: anorexia nervosa, bulimia nervosa
Chronic disruption in sexual functioning, behavior, or preferences: sexual dysfunctions, paraphilias,
sexual-identity disorder
Sleep disorders Chronic sleep problems: primary insomnia, primary hypersomnia, sleep-terror disorder, sleepwalking
disorder
Impulse-control disorders Chronic inability to resist impulses, drives, or temptations to perform certain acts that are harmful to
the self or others: pathological gambling, kleptomania, pyromania, intermittent explosive disorder
Adjustment disorders A maladaptive reaction to a clear stressor, such as divorce or business difficulties, that first occurs within
3 months after the onset of the stressor
Conditions or problems that are worth noting because they cause significant impairment, such as
relational problems, problems related to abuse or neglect, medication-induced movement disorders,
and psychophysiological disorders
Source: Adapted from Diagnostic and Statistical Manual of Mental Disorders (4th ed.), 1994, Washington, DC: American Psychiatric Association.
Other conditions that may be a
focus of clinical attention
Sexual disorders and sexualidentity
disorder
Schizophrenia and other
psychotic disorders
Mental disorders due to a
general medical condition
Delirium, dementia, amnesia,
and other cognitive disorders
Disorders usually first diagnosed
in infancy, childhood, and
adolescence
Table 15-5
DSM-IV-TR. Text revision of the fourth,
and most recent, edition of the American
Psychiatric Association’s classification of
psychiatric disorders, the Diagnostic and
Statistical Manual of Mental Disorders.
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As already stated, any classification of psychiatric disorders is to some extent arbitrary
and unavoidably depends on prevailing cultural views. A good example is the
social definition of abnormal sexual behavior. From its inception, theDSM listed homosexual
behavior as pathological. Since 1980, however, the Manual has omitted this “disorder.”
The revision is due to changed cultural beliefs about what sexual abnormality is
as much as it is to new findings from research on the neurological bases of sexual preference
(Chapter 11).
One continually emerging means of looking for indicators of behavioral disorders
is brain imaging, including MRI and PET (Chapters 9 and 14). These imaging tools are
not currently used clinically, but they may soon be used both to classify disorders and
to monitor the effectiveness of treatment.
To be useful, imaging tests must be sensitive enough to detect
unique features of brain disorders but specific enough to rule out similar
conditions. The latter feature is problematic, inasmuch as many
behavioral disorders display similar abnormalities. Enlarged ventricles
may appear in schizophrenia, Alzheimer’s disease, alcoholism, or
head trauma, for example. Nonetheless, neuroscientists have begun
using imaging technology to shed light on behavioral disturbances.
In an impressive example, research teams led by Judith
Rapoport, Paul Thompson, and Arthur Toga compared the brains of
healthy adolescents with those diagnosed with childhood-onset
schizophrenia (see review by Sowell et al., 2004). Figure 15-3 shows
that, between the ages of 13 and 18, the children who developed
schizophrenia showed a remarkable loss of gray matter in the cerebral
cortex. This loss was correlated with the onset of a variety of behavioral disturbances
characteristic of the disease. Such analyses could provide an important aid to
treatment because early detection of schizophrenia ought to provide a rationale for
proper drug treatment that may slow down the progress of the disease.
Not all disorders will show such obvious loss of tissue, but they may show abnormal
blood flow or metabolism that can be detected either by fMRI or PET. The PET images
in Figure 15-4 illustrate the metabolic changes in adult-onset schizophrenia, showing
an obvious abnormality in activity in the prefrontal cortex. Note that this area does not
show loss of gray matter in the early-onset-schizophrenia MRI study reproduced in Figure
15-3. Therefore the two diseases seem likely to have different origins.
Combining behavioral diagnoses with neuroimaging may enable movement beyond
symptom checklists like those published in the DSM to more-objective medical
diagnoses. Further, imaging analyses may provide treatments to reduce the severity of
such serious disorders as schizophrenia and Alzheimer’s disease. Remember, however,
that not all brain pathology will be detected by using current imaging techniques.
Part of the challenge for the future is to improve current techniques and to develop
others that can identify more-subtle molecular abnormalities
in the nervous system.
Treatments for Disorders
We have encountered disorders of brain and behavior in every
chapter of this book, especially in the Focus boxes. Indexed in
Table 1-1 on page 6, the variety of disorders is broad, but an inclusive
list would consist of some 2000 entries. The long-term
prospects for curing organic or behavioral disorders on the
macro level depend on the ability to treat structural and biochemical
abnormalities at the micro level.
Normal adolescents Schizophrenic subjects
0 –1 –2 –3 –4 –5
Average annual loss (%)
Figure 15-3
Early-Onset Schizophrenia A
comparison of three-dimensional maps
derived from MRI scans reveals that,
compared with healthy teenagers aged
13 to 18 (map shown at left), patients
with childhood onset schizophrenia
(map shown at right) have widespread
loss of gray matter across the cerebral
hemispheres. Courtesy of Paul Thompson
and Arthur W. Toga, University of California
Laboratory of Neuro Imaging, Los Angeles, and
Judith L. Rapoport, National Institute of Mental
Health.
Figure 15-4
Adult-Onset Schizophrenia PET
scans of the brains of (left) an adult
schizophrenia patient and (right) a
person who does not have schizophrenia.
Note the abnormally low blood flow in
the prefrontal cortex at the top of the
left-hand scan.
Hank Morgan/Photo Researchers
Hank Morgan/Photo Researchers
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On the organic side, the unifying characteristic is some underlying nervous system
abnormality. Organic abnormalities include genetic disorders (such as Huntington’s
chorea), developmental disorders (such as autism), infectious diseases (such as meningitis),
nervous system injuries (such as brain or spinal-cord trauma), and degenerative
conditions (such as Alzheimer’s disease). On the structural side, organic disorders
include the congenital absence of neurons or glia, the presence of abnormal neurons or
glia, the death of neurons or glia, and neurons or neural connections with unusual
structures. Similarly, abnormalities may appear in the biochemical organization or operation
of the nervous system. Biochemical abnormalities include disordered proteins in
cell-membrane channels, low or high numbers of neuroreceptors, low or high numbers
of molecules, especially neurotransmitters or hormones, and any improper balances.
The ultimate clinical problem for behavioral
neuroscience is to apply its knowledge to generate
treatments that can restore a disordered brain
(and mind) to the range of normalcy. This challenge
is daunting because the first task is so difficult:
learning the cause of a particular behavioral
disturbance. Few behavioral disorders have as
simple a cause as PKU does.Most, like schizophrenia,
are extremely complex. Still, a variety of more
or less effective treatments for a range of behavioral
disorders have been developed, as summarized
in Table 15-6.
Treatments fall into four general categories:
neurosurgical, pharmacological, electrophysiological,
and behavioral. In very invasive neurosurgical
treatment, the skull is opened and some
intervention is performed on the brain. Pharmacotherapy
is less invasive. A chemical that affects
the brain is either ingested or injected. Noninvasive
physiological and behavioral treatments manipulate
the body or the experience,which in turn
influences the brain. As you will see, each treatment
category has a specific objective.
NEUROSURGICAL TREATMENTS
Historically, neurosurgical manipulations of the
nervous system with the goal of directly altering it
have been largely reparative, such as when tumors
are removed or arteriovenous malformations are
corrected. More recently, however, neurosurgical approaches aim at altering brain activity
to alleviate some behavioral disorder. The surgery either damages some dysfunctional
area of the brain or stimulates dysfunctional areas with electrodes.
The treatment of Parkinson’s disease can employ both neurosurgeries (Boucai,Cerquetti,
& Merello, 2004). In the first technique, an electrode is placed into the motor
thalamus and an electric current is used to damage neurons that are responsible for producing
the tremor characteristic of Parkinson’s. In the second neurosurgery, deep brain
stimulation (DBS), an electrode fixed in place in the globus pallidus or subthalamic
nucleus is connected to an external electrical stimulator that can be activated by the patient
to facilitate normal movements.
Another neurosurgical strategy is highly experimental, as well as controversial. In
Chapter 6, you learned that the brain develops in a fixed sequence: from cell division
to cell differentiation to cell migration to synaptogenesis. If a region of the brain is
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 579
Summary of Treatments of Brain and Behavior
Chapter in which an
Treatment example is discussed
Neurosurgical
Damage to dysfunctional area (e.g., Parkinson’s disease) 10
Implantation of embryonic or endogenous stem cells to 13
regenerate lost tissue
Deep brain stimulation (e.g., implantation of stimulation 10
electrode to control tremor in Parkinson’s disease)
Removal of abnormal tissue (e.g., epilepsy, tumor) 9
Repair of abnormality (e.g., arteriovenous malformations) 9
Pharmacological
Antibiotic or antiviral agents or both (e.g., encephalitis) 2
Drugs to alter neurochemistry 7
Neurotrophic factors 13
Nutritional 11
Electrophysiological
Direct electrical brain stimulation 15
Electroconvulsive therapy (ECT) 15
Transcranial magnetic stimulation (TMS) 14
Behavioral
Behavioral training (e.g., speech therapy, cognitive therapy) 13
Psychotherapy 15
Table 15-6
Deep brain stimulation (DBS).
Neurosurgery to facilitate normal
movements, in which an electrode is
fixed in place in the globus pallidus or
subthalamic nucleus and connected to an
external electrical stimulator controlled
by the patient.
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functioning abnormally or if it is diseased or dead, it should be possible to return this
region to the embryonic state and regrow a normal region.
This technique has a science-fiction ring to it, but it may someday be feasible. In
laboratory rats, for example, stem cells can be induced by neurotrophic factors to generate
new cells that can migrate to the site of an injury (Chapter 6). This process may
not be practical in a large brain such as that possessed by humans, but the principle of
using stem cells to generate new neurons still holds. Stem cells might be placed directly
into a dysfunctional region and then supplied with different growth factors that would
stimulate them to generate a functional region.
Where would the stem cells come from? In the 1980s, surgeons experimented with
implanting fetal cells into adult brains (see “The Case of the Frozen Addict “on page
171), but this approach has had limited success. Another idea comes from the discovery
that multipotent stem cells in other body regions, such as in bone marrow, appear
to be capable of manufacturing neural stem cells.
If the use of multipotent stem cells proves to be a practical way of generating neural
stem cells, it should be possible to take bone marrow cells from a person, place them
in a special culture medium to generate thousands or millions of stem cells, and then
place these stem cells into the damaged brain. The challenge is to get the cells to differentiate
appropriately and develop the correct connections. At present, this challenge
is still formidable, but meeting it is well within the realm of possibility.
Transplanting stem cells is being seriously talked about today as a treatment for
disorders such as stroke. In fact, Douglas Kondziolka and his colleagues (2000) tried
cell transplants with a sample of 12 stroke victims. They harvested progenitor cells
from a rare tumor known as a teratocarcinoma. The tumor cells were chemically altered
to develop a neuronal phenotype, and then between 2 million and 6 million cells
were transplanted into regions around the stroke.
The patients were followed for a year, and, for 6 of them, PET scans showed an increase
in metabolic activity in the areas that had received the transplanted cells, indicating
that the transplants were having some effect on the host brain. Behavioral
analyses also showed some improvement in these patients. This study is only the first
of its type, and the behavioral outcome was modest, but it does show that such a neurosurgical
treatment may be feasible.
ELECTROPHYSIOLOGICAL TREATMENTS
Treating the mind by treating the body is an ancient notion. In the 1930s, researchers
used insulin to lower blood sugar and produce seizures as a treatment for depression.
By the 1950s, insulin therapy had been replaced by electroconvulsive therapy (ECT),
the first electrical brain-stimulation treatment.
Electroconvulsive therapy was developed as a treatment for depression and, although
its mode of action was not understood, it did prove useful in some patients. Although
rarely used today,ECT is still sometimes the only treatment that works for people
with severe depression.One reason may be that ECT stimulates the production of a variety
of neurotrophic factors, especially BDNF (brain-derived neurotrophic factor).
Significant problems with ECT include the massive convulsions caused by the electrical
stimulation. These convulsions normally require large doses of medications to
prevent them. Another problem is that ECT leads to memory loss, a symptom that can
be quite troublesome with repeated ECT treatments.
A newer research technique described in Chapter 14, transcranial magnetic stimulation
(TMS), uses magnetic rather than electrical stimulation. To date, the only widespread
clinical application of TMS is as a treatment for depression. Clinical applications
for TMS are growing, as reviewed in “Treating Behavioral Disorders with TMS.”
Transcranial magnetic stimulation is a far less drastic treatment than ECT and will
probably become a far more widely used treatment in the coming decade (Rossi &
580 ! CHAPTER 15
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Treating Behavioral Disorders with TMS
Focus on New Research
In transcranial magnetic stimulation, a magnetic field is
placed over the scalp to affect the underlying brain regions.
The advantage of TMS is that it can be applied to localized
brain regions, or focal areas, thought to be implicated in specific
disorders. If the magnetic field is sufficiently strong, an
area of cortex as small as a quarter can be activated with the
use of this technique.
The primary clinical use of TMS is for depression. Findings
from brain-imaging studies show that depression is associated
with reduced metabolic activity in the dorsolateral
prefrontal cortex. Stimulation of the region might help to resolve
the depression.
The results of controlled clinical studies of drug-resistant
patients show that daily stimulation of the left dorsolateral
prefrontal cortex may produce significant reductions in depressive
symptoms compared with sham TMS treatment (e.g.,
George et al., 1997). One difficulty is that the relief may be
transient, possibly because the stimulation does not reach
deeper regions of the hemisphere, such as the limbic cortex.
Recent experiments are attempting to induce controlled
seizures with TMS to create an ECT-like effect. With the energy
transfer so much weaker in TMS, researchers reason that
TMS would not produce the drastic side effects of ECT (Sporn
et al., 2004).
Schizophrenia also may also be a good candidate for
TMS therapy (Haraldsson et al., 2004). The clear pathology
in the frontal lobe, for example, would be relatively easy to
target. Similarly, auditory hallucinations originate in the auditory
cortex and this region, too, would be an accessible
target for TMS. Studies have been done on both targets.
High-frequency TMS to the prefrontal cortex has been
promising, at least for negative symptoms. Several studies
using TMS to specifically treat auditory hallucinations are
ongoing. The general finding is that daily TMS for only about
20 min produces significant reduction in hallucination frequency
in most, but not all, schizophrenia patients studied
(e.g., Hoffman et al., 2003). Other symptoms were unchanged.
Long-term follow-ups showed a slow return of the
hallucinations.
One TMS study of schizophrenia patients is especially
intriguing. Paul Fitzgerald and colleagues (2004) wondered
if repeated stimulation might make the brain more plastic. If
so, would there be a difference in schizophrenic subjects?
The authors stimulated the motor cortex of control subjects
and found that a 15-min train of TMS produced a
change in the excitability of the motor cortex to later short
pulses of TMS. They concluded that the train of TMS had produced
a plastic change in the brain, likely by reducing cortical
inhibition.
Curiously, the same procedure induced no similar plastic
change when used with schizophrenia subjects. Two implications
of this finding are:
1. The failure to record a persisting change in the schizophrenia
subjects suggests that TMS is having somewhat different
effects in the controls and patients. The difference in
effects may explain why the effects of TMS are apparently
not permanent. To produce persisting changes in cortical
excitability, schizophrenia patients may require much
longer courses of stimulation than do control subjects.
2. The reduced plasticity in the patients may account for the
memory problems of schizophrenia patients. If the brain
is less plastic, producing the neural changes necessary
for learning will be more difficult.
TMS has not yet been used clinically in anxiety disorders,
in large part because neuroimaging studies have not yet
identified specific targets. There is optomism that such targets
will be found with more-sensitive PET and fMRI analyses,
and TMS could then be tried as a way to influence
activity in such regions (Boland & Keller, 2004).
In clinical therapy for depression, transcranial magnetic stimulation
influences action potentials in a localized brain area.
George Ruhe/The New York Times
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Rossini, 2004). One advantage that contributes to reduced side effects is the precision
of TMS. The magnetic stimulation can be applied narrowly, to a focal area, rather than
diffusely, as in ECT. And the prospective range of applications for TMS is broad.
Electrical stimulation may also have a role in treating certain neurological diseases.
As noted earlier, Parkinson’s disease can be treated with the implantation of electrodes
into the putamen. In both animal studies and preliminary studies in human stroke patients,
focal electrical stimulation of the regions next to tissue damaged by stroke is now
being used. The electrical activation of these adjacent regions appears to increase the
production of synapses and to enhance function (Teskey et al., 2003).
PHARMACOLOGICAL TREATMENTS
Two developments in the 1950s led to a pharmacological revolution in the treatment
of behavioral disorders:
1. A drug used to premedicate surgical patients was discovered to have antipsychotic
properties. This finding led to the development of phenothiazines as a treatment
for schizophrenia, and, in the next 40 years, these neuroleptic drugs became increasingly
more selective and effective.
2. A new class of antianxiety drugs was invented—namely, the anxiolytics—and
medications such as Valium quickly became the most widely prescribed drugs in
the United States.
The power of these two classes of drugs to change disordered behavior revolutionized
the pharmaceutical industry. That revolution is just now reaping major rewards
with the development of the second-generation, or so-called atypical, antidepressants
such as Prozac (Chapter 7). These SSRIs (selective serotonin reuptake inhibitors) hold
promise in the restoration of more-normal behavior in people with a wide range of disorders.
Another revolutionary pharmaceutical, L-dopa, provided the first treatment for
a serious motor dysfunction in Parkinson’s disease (Chapter 5). L-Dopa’s effectiveness
led to optimism that drugs might be developed as “magic bullets” to correct the chemical
imbalances found in Alzheimer’s disease and other disorders.
Neuroscientists now know that most behavioral disorders cannot be reduced to a
single chemical abnormality. Pharmacological treatments need considerable refinement;
they are no panacea for neurobiological dysfunctions. Nonetheless, for many
people, drug treatment provides relief from a host of mental and motor problems.
Pharmacological treatments have their downsides. Significant side effects top the
list, and long-term effects may create new problems. Consider a person who receives
antidepressant medication.Although the drug may ease the depression, it may produce
unwanted side effects, including decreased sexual desire, fatigue, and sleep disturbance.
These last two effects may also interfere with cognitive functioning.
Thus, although the medication is useful for getting the person out of the depressed
state, it may produce other symptoms that are themselves disturbing and may complicate
the person’s recovery. Furthermore, in cases in which the depression is related to
life events, a drug does not provide a person with the behavioral tools needed to cope
with an adverse situation. As some psychologists say, “A pill is not a skill.”
A second example of drug treatments’ negative side effects can be seen in many people
being treated for schizophrenia with neuroleptics. These antipsychchotic drugs act
not only on the mesolimbic dopamine system, which is likely to be functioning abnormally
in the schizophrenia patient, but also on the nigrostriatal dopaminergic system,
which controls movement. It is therefore common for patients who take neuroleptics
for a prolonged period to begin having motor disturbances. Tardive dyskinesia, an inability
to stop the tongue from moving, is a motor symptom.
582 ! CHAPTER 15
Tardive dyskinesia. Inability to stop
the tongue from moving; motor side effect
of neuroleptic drugs.
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Movement-disorder side effects often persist long after the medication has been
stopped. Taking drugs for behavioral disorders, then, does carry some risk. Rather than
acting like “magic bullets,” these medications can sometimes act like “magic shotguns.”
BEHAVIORAL TREATMENTS
Although all psychiatric disorders are ultimately related to the nervous system, environmental
factors often contribute to them as well. The influence of environmental
factors on behavior is illustrated by the simple fact that our behavior in the context of
a formal social gathering is quite different from that in the company of our closest
friends. Social and cultural factors affect how the brain operates to produce behaviors,
normal as well as abnormal ones.We are a long way from understanding exactly how
environmental factors influence brain activity or promote pathological behaviors at
specific times and places.
Treatments for behavioral disorders need not be direct biological or medical interventions.
Just as the brain can alter behavior, behavior can alter the brain (Chapter
11). Therefore, behavioral treatments often focus on key environmental factors that influence
how a person acts.
As behavior changes in response to these treatments, the brain is affected as well.
An example is the treatment of generalized anxiety disorders, as illustrated by the case
of G. B. in Chapter 11. Although G. B. required immediate treatment with antianxiety
medication, the long-term treatment entailed changing his behavior. His anxiety disorder
was not simply a problem of abnormal brain activity. It was also a problem of
experiential and social factors that fundamentally altered his perception of the world.
In the past 40 years, psychologists have developed two general ways to change behavior,
behavioral therapies and cognitive therapies. Behavioral therapies apply wellestablished
learning principles to eliminate unwanted behaviors. For example, if a
person is debilitated by a fear of insects, there is little point in looking for inner causes.
Rather, the behavioral therapist will try to replace the maladaptive behaviors with more
constructive ways of behaving, which might include training to relax or systematic exposure
to unthreatening insects (butterflies) and then gradual exposure to morethreatening
insects (bees), the latter technique being called systematic desensitization.
Cognitive therapies take the perspective that thoughts intervene between events
and emotions. Consider responses to losing a job. One thought could be that “I am a
loser, life is hopeless.” An alternate thought is that “the boss is a jerk and he did me a
favor.”
You can imagine that the former cognitions might lead to depression, whereas the
latter would not.Cognitive therapies challenge a person’s self-defeating attitudes and assumptions.
Such therapy can be quite important for people with brain injuries, too, because
it is easy for people to think that they are “crazy” or “retarded” after brain injury.
If one of your relatives or friends were to have a stroke and become aphasic, you
would expect the person to receive speech therapy, which is a form of behavioral treatment
for an injured brain. The logic in speech therapy is that, by practicing (relearning)
the basic components of speech and language, the patient should be able to regain
at least some of the lost function. The same logic can be applied to other types of behavioral
disorders, whether motor or cognitive.
Therapies for cognitive disorders resulting from brain trauma or dysfunction aim
to retrain people in the fundamental cognitive processes that they have lost. Although
cognitive therapy seems as logical as speech therapy after a stroke, the difficulty is that
such therapy assumes that we know what fundamental elements of cognitive activity
are meaningful to the brain. Cognitive scientists are far from understanding these elements
well enough to generate optimal therapies. Still, neuropsychologists such as
George Prigatano and Catherine Mateer and their respective colleagues are developing
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 583
Behavioral therapy. Treatment that
applies learning principles, such as
conditioning, to eliminate unwanted
behaviors.
Cognitive therapy. Psychotherapy
based on the perspective that thoughts
intervene between events and emotions,
and thus the treatment of emotional
disorders requires changing maladaptive
patterns of thinking.
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neurocognitive programs that are able to improve functional outcomes following
traumatic brain injury and stroke (Prigatano, 1986; Sohlberg & Mateer, 1989).
In addition to disturbances in cognitive activities such as language and memory,
people’s emotions may be disturbed. In the 1920s, Sigmund Freud developed the idea
that talking about such emotional problems enables people to have insights into their
causes that can serve as treatments, too. These “talking cures,” as well as other forms of
psychological intervention, may be broadly categorized as psychotherapies.
Since Freud’s time, many ideas have been put forth about the best type of behavioral
therapy for emotional disorders. The key point here is that, for many disorders,
whether neurological or psychiatric, medical treatments may be ineffective unless patients
also receive psychotherapy. Indeed, in many cases, the only effective treatment
lies in treating the unwanted behaviors directly.
Consider a 25-year-old woman pursuing a promising career as a musician who
suffered a traumatic brain injury in an automobile accident. After the accident, she
found that she was unable to read music.Not surprisingly, she soon became depressed.
Part of her therapy required that she confront her disabling cognitive loss by talking
about it rather than by simply stewing about it. Only when she pursued psychotherapy
did she begin to recover from her intense depression.
For many people with cognitive impairments resulting from brain disease or
trauma, the most effective treatment for their depression or anxiety is to help them adjust
by encouraging them to talk about their difficulties. In fact, group therapy, which
provides such encouragement, is standard treatment in brain-injury rehabilitation
units. In this regard, Fred Linge, whose case history begins Chapter 1 of this book, has
played a major role in establishing support groups for people with head trauma. These
groups serve as a form of group therapy.
You may be thinking that, although behavioral therapies may be of some help in
treating brain dysfunction, the real solution must lie in altering the brain and its activities.
This notion may be valid, but remember a key fact: because every aspect of behavior
is the product of brain activity, it can be argued that behavioral therapies do act
by changing brain function. That is, not only does altering the brain change our behavior,
but altering our behavior also changes the brain.
If people can change the way that they think and feel about themselves or some aspect
of their lives, this change has taken place because “talking about their problems”
has altered the way in which their brains function. In a sense, then, behavioral therapies
can be viewed as “biological interventions.” These interventions may sometimes
be helped along by drug treatments that make the brain more receptive to change
through behavioral therapies. In this way, drug treatments and behavioral therapies
may have synergistic effects, each helping the other to be more effective.
In Review .
Epidemiological studies have been used to identify and classify behavioral disorders, but
little is known about the relation between these disorders and specific biological pathologies.
Rather, the classification schemes such as the DSM-IV are essentially checklists of
likely symptoms. Therapies for brain and behavioral disorders range from the very invasive
(neurosurgery), moderately invasive ((pharmacological or electrophysiological brain
stimulation), to indirect, noninvasive cognitive rehabilitation and other behavioral therapies.
Today, none of these therapies are completely effective, but, as more is learned about
the details of brain–behavior relations, we can look forward to improved recovery from a
wide range of behavioral dysfunctions that affect a large percentage of the population.
584 ! CHAPTER 15
Psychotherapy. Talking therapy derived
from Freudian psychoanalysis and other
psychological interventions.
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UNDERSTANDNG AND TREATING
NEUROLOGICAL DISORDERS
We now review in more detail several common neurological disorders: brain trauma,
stroke, epilepsy, multiple sclerosis, and neurodegenerative disorders. In our lifetimes,
each of us likely will have at least one close friend or relative develop one of these disorders,
even if we ourselves escape them. Their causes are understood, at least in a
general sense, although, for most, development of rehabilitative treatments remains,
unfortunately, primitive.
Traumatic Brain Injury
As detailed in Chapter 1, traumatic brain injury is a common result of head impacts
with other objects—as can occur in automobile and industrial accidents—and of
sporting injuries. Cerebral trauma, or injury from a blow to the head, is the most common
form of brain damage in people under age 40. In one telephone survey in Sweden,
cerebral concussion, defined as an injury resulting from a violent blow or shock
producing at least brief unconsciousness, was reported by 5 percent of those interviewed.
In addition, another estimated 5 percent of the general population are likely to
have suffered concussion without obvious unconsciousness, although they would have
experienced some confusion about the events before and after the blow to the head.
The two most important factors in the incidence of head trauma are age and sex.
Children and elderly people are more likely to suffer head injuries from falls than are
others, and males between 15 and 30 are very likely to incur brain injuries, especially
from automobile and motorcycle accidents (Figure 15-5). A child’s chance of suffering
significant traumatic brain injury before he or she is old enough to drive is 1 in 30.
SYMPTOMS AND OUTCOME OF BRAIN TRAUMA
Traumatic brain injury can affect brain function by causing direct damage to the brain.
Trauma can disrupt the brain’s blood supply; induce bleeding, leading to increased intracranial
pressure; cause swelling, leading to increased intracranial pressure; expose
the brain to infection; and scar brain tissue (the scarred tissue becomes a focus for later
epileptic seizures).
Traumatic brain injuries are commonly accompanied by a loss of consciousness
that may be brief (minutes) or prolonged (coma). The duration of unconsciousness
can serve as a measure of the severity of damage, because it correlates directly with
mortality, intellectual impairment, and deficits in social skills. The longer the coma
lasts, the greater the possibility of serious impairment and death.
Two kinds of behavioral effects result from traumatic brain injuries: (1) impairment
of the specific functions mediated by the cortex at the coup (the site of impact)
or countercoup (opposite side) lesion and (2) more-generalized impairments from
widespread trauma throughout the brain. Discrete impairment is most commonly associated
with damage to the frontal and temporal lobes, the brain areas most susceptible
to traumatic brain injuries.
More-generalized impairment results from minute lesions and lacerations scattered
throughout the brain. Tears due to movement of the hemispheres in relation to
each other are characterized by a loss of complex cognitive functions, including reductions
in mental speed, concentration, and overall cognitive efficiency. Patients generally
complain of poor concentration or lack of ability.
They fail to do things as well as they could before the injury, even though their intelligence
rating may still be well above average. In fact, in our experience, bright people
seem to be the most affected by traumatic brain injuries, in large part because they
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 585
Cases per 100,000 population per year
10 20 30 40 50 60 70 80+
700
600
500
400
300
200
100
0
Age (years)
Male
Female
Figure 15-5
Incidence Rates of Head Trauma
These statistics were collected from 1965
through 1974 in Olmsted County,
Minnesota. Nationwide, the proportions
remain remarkably consistent a
generation later. Adapted from Annegers et
al., 1980.
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are acutely aware of any loss of cognitive skill that prevents them from returning to
their former competence level.
Traumatic brain injuries that damage the frontal and temporal lobes also tend to
have significant effects on personality and social behavior. According to Muriel Lezak
(2003), few victims of traffic accidents who have sustained severe head injuries ever resume
their studies or return to gainful employment. If they do reenter the work force,
they do so at a lower level than before their accidents.
One frustrating problem with traumatic brain injuries is misdiagnosis: their
chronic effects often are not accompanied by any obvious neurological signs or abnormalities
in CT or MRI scans, and the patients may therefore be referred for psychiatric
or neuropsychological evaluation.A new imaging technique,magnetic resonance
spectroscopy (MRS) is promising for accurate diagnosis of traumatic brain injuries.
Magnetic resonance spectroscopy, a modification of MRI, can identify changes in specific
markers of neuronal function.
One such marker is N-acetylaspartate (NAA), the second most abundant amino
acid in the human brain (Tsai & Coyle, 1995). The level of NAA expression assesses the
integrity of neurons, and deviations from normal levels (up or down) can be taken as
a marker of abnormal brain function. People with traumatic brain injuries show a
chronic decrease in NAA, which correlates with the severity of the injury (Brooks,
Friedman, & Gasparovic, 2001). Although not widely used clinically yet, MRS promises
to be a useful tool not only in identifying brain abnormalities but also in monitoring
the cellular response to therapeutic interventions.
RECOVERY FROM TRAUMATIC BRAIN INJURY
Although it is often stated that recovery from head trauma may continue for 2 to 3
years, there is little doubt that the bulk of the cognitive recovery occurs in the first 6 to
9 months. Recovery of memory functions appears to be somewhat slower than recovery
of general intelligence, and the final level of memory performance is lower than for
other cognitive functions. Harvey Levin and his colleagues (1982) suggested that people
with brainstem damage, as inferred from oculomotor disturbance, have a poorer
cognitive outcome, and this poorer outcome is probably true of people with initial dysphasias
or hemipareses as well.
Although the prognosis for significant recovery of cognitive functions is good,
there is less optimism about the recovery of social skills or normal personality, areas
that often show significant change. Findings from numerous studies support the conclusions
that the quality of life—in regard to social interactions, perceived stress levels,
and enjoyment of leisure activities—is significantly reduced after traumatic brain injury
and that this reduction is chronic. There have been few attempts to develop tools
to measure changes in psychosocial adjustment in brain-injured people; so we must
rely largely on subjective descriptions and self-reports, which provide little information
about the specific causes of these problems.
Stroke
In Chapter 2, we described the symptoms and aftereffects of stroke, an interruption of
blood flow either from the blockage of a vessel or from the bleeding of a vessel.Although
we may be able to point to a specific immediate cause of a stroke, this initial event merely
sets off a sequence of damaging events that progresses even if the blood flow is restored.
Stroke results in a lack of blood, called ischemia, followed by a cascade of cellular events
that wreak the real damage. Changes at the cellular level can seriously compromise not
only the injured part of the brain but other brain regions as well.
586 ! CHAPTER 15
Magnetic resonance spectroscopy
(MRS). Modification of MRI in which
changes in specific markers of neuronal
function can be identified; promising for
accurate diagnosis of traumatic brain
injuries.
Ischemia. Lack of blood to the brain as
a result of stroke.
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EFFECTS OF STROKE
Consider what happens after a stroke that interrupts the blood supply to
one of the cerebral arteries. In the first seconds to minutes after ischemia,
as illustrated in Figure 15-6, changes begin in the ionic balance of the affected
regions, including changes in pH and in the properties of the cell
membrane. These ionic changes result in a variety of pathological events,
such as the release of massive amounts of glutamate and the prolonged
opening of calcium channels.
The open calcium channels in turn allow toxic levels of calcium to enter
the cell, not only producing direct toxic effects but also instigating various
second-messenger pathways that can prove to be harmful to the neurons.
In the ensuing minutes to hours, mRNA is stimulated, altering the production
of proteins in the neurons and possibly proving to be toxic to the cells.
Next, brain tissues become inflamed and swollen, threatening the integrity of cells
that may be far removed from the stroke site. Finally, a form of neural shock, referred
to as diaschisis, occurs. Thus, not only is localized neural tissue and its function lost
but areas related to the damaged region also suffer a sudden withdrawal of excitation
or inhibition. Such sudden changes in input can lead to a temporary loss of neural
function, both in areas adjacent to an injury and in regions that may be quite distant
in the nervous system.
A stroke may also be followed by changes in the metabolism of the injured hemisphere,
its glucose utilization, or both, which may persist for days. Like diaschisis, these
metabolic changes can have severe effects on the functioning of otherwise normal tissue.
For example, after a cortical stroke, metabolic rate has been shown to decrease
about 25 percent throughout the rest of the hemisphere.
TREATMENTS FOR STROKE
The ideal treatment is to restore blood flow in blocked vessels before the cascade of nasty
events begins.One such clot-busting drug, described in Chapter 2, is tissue plasminogen
activator (t-PA). The difficulty with t-PA is that it must be administered within 3 hours
to be effective. Only a small percentage of stroke patients currently arrive at the hospital
soon enough, in large part because stroke is often not considered to be an emergency.
Other drugs called neuroprotectants can be used to try to block the cascade of
postinjury events, but to date these drugs have not proved to be as helpful as was
hoped.When the course of the stroke has led to dead brain tissue, the only treatments
that can be beneficial are those that facilitate plastic changes in the brain. Examples are
speech therapy or physical therapy. Although it would seem logical that therapies
would be beneficial, there is surprisingly little evidence regarding which poststroke
treatments are actually helpful or what timing or duration is most beneficial.
Epilepsy
In epilepsy, a person suffers recurrent seizures that register on an EEG and are associated
with disturbances of consciousness (Chapter 4). The character of epileptic
episodes can vary greatly, and seizures are common; 1 person in 20 will experience at
least one seizure in his or her lifetime. The prevalence of multiple seizures is much
lower, however: about 1 in 200.
Epileptic seizures are classified as symptomatic if they can be identified with a specific
cause, such as infection, trauma, tumor, vascular malformation, toxic chemicals,
very high fever, or other neurological disorders. Seizures are idiopathic if they appear
spontaneously and in the absence of other diseases of the central nervous system.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 587
Seconds
to minutes
Hours
to days
Weeks to
months
0
50
Response (%)
100
Ionic
changes
Second
messengers
mRNA Proteins Inflammation Recovery
Figure 15-6
Results of Ischemia A cascade of
events takes place after blood flow is
blocked as a result of stroke. Within
seconds, ionic changes at the cellular
level spur changes in second-messenger
molecules and RNA production. Changes
in protein production and inflammation
follow and resolve slowly, in hours to
days. Recovery begins within hours to
days and continues from weeks to
months or years.
Diaschisis. Neural shock that follows
brain damage in which areas connected
to the site of damage show a temporary
arrest of function.
Neuroprotectant. Drug used to try to
block the cascade of poststroke neural
events.
Symptomatic seizure. Identified with a
specific cause, such as infection, trauma,
tumor, vascular malformation, toxic
chemicals, very high fever, or other
neurological disorders.
Idiopathic seizure. Appears
spontaneously and in the absence of
other diseases of the central nervous
system.
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Table 15-7 summarizes the great variety of circumstances that appear to precipitate
seizures. The range of circumstances is striking, but seizures do have a consistent
feature: the brain is most epileptogenic when it is inactive and the patient is sitting still.
Although epilepsy has long been known to run in families, its incidence is lower
than a one-gene model would predict.More likely, certain genotypes carry a predisposition
to seizure, given certain environmental circumstances. The most remarkable
clinical feature of epileptic disorders is the widely varying intervals between attacks—
from minutes to hours to weeks or even years. In fact, it is almost impossible to describe
a basic set of symptoms to be expected in all, or even most, people with epilepsy.
Nevertheless, three particular symptoms are found in within the variety of epileptic
episodes:
1. An aura, or warning, of impending seizure may take the form of a sensation—an
odor or a noise—or it may simply be a “feeling’’ that the seizure is going to occur.
2. Loss of consciousness ranges from complete collapse in some people to simply staring
off into space in others. The period of lost consciousness is often accompanied
by amnesia, including the victim forgetting the seizure itself.
3. Seizures commonly have a motor component, but, as noted, the movement characteristics
vary considerably. Some people shake; others exhibit automatic movements,
such as rubbing the hands or chewing.
In Chapter 4, we described a diagnosis of epilepsy, confirmed by EEG. Some
seizures, however, are difficult to document except under special circumstances (e.g.,
an EEG recorded during sleep). Moreover, not all persons with an EEG suggestive of
epilepsy actually have seizures. Some estimates suggest that as many as 4 people in 20
simply have abnormal EEG patterns, many more than the 1 in 200 thought to suffer
from epilepsy (see Table 15-4). Among the many types of epileptic seizures, we compare
only two here: focal and generalized seizures.
FOCAL SEIZURES
Focal seizures begin in one place and then spread out. John Hughlings Jackson hypothesized
in 1870 that focal seizures probably originate from the point (focus) in the neocortex
representing the region of the body where the movement is first seen.He was later
proved correct. In Jacksonian focal seizures, for example, the attack begins with jerking
movements in one part of the body—a finger, a toe, or the mouth—and then spreads to
adjacent parts. If the attack begins with a finger, the jerks might spread to other fingers,
then the hand, the arm, and so on, producing so-called “Jacksonian marches.”
588 ! CHAPTER 15
Factors That May Precipitate Seizures in Susceptible Persons
Source: Adapted from Behavioral Neurobiology (p. 5), by J. H. Pincus and G. J. Tucker, 1974, New York: Oxford
University Press.
Emotional stress
Drugs
Phenothiazines
Analeptics
Tricyclic antidepressants
Alcohol
Excessive
anticonvulsants
Trauma
Hormonal changes
Menses
Puberty
Adrenal steroids
Adrenocorticotrophic
hormone (ACTH)
Fever
Hyperventilation
Sleep
Sleep deprivation
Sensory stimuli
Flashing lights
Reading, speaking, coughing
Laughing
Sounds: music, bells
Table 15-7
Focal seizure. Category of seizure that
begins locally (at a focus) and then
spreads out to adjacent areas.
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Complex partial seizures, another focal type, originate most commonly in the temporal
lobe and somewhat less frequently in the frontal lobe. Complex partial seizures
are characterized by three common manifestations:
1. subjective experiences that presage the attack—for example, forced, repetitive
thoughts, alterations in mood, feelings of deja vu, or hallucinations;
2. automatisms—repetitive stereotyped movements such as lip smacking or chewing
or activities such as undoing buttons; and
3. postural changes, such as when the person assumes a catatonic, or frozen, posture.
GENERALIZED SEIZURES
Generalized seizures lack focal onset and often occur on both sides of the body. The
grand mal (“big bad”) attack is characterized by loss of consciousness and stereotyped
motor activity. Patients typically go through three stages: (1) a tonic stage, in which the
body stiffens and breathing stops; (2) a clonic stage, in which there is rhythmic shaking;
and (3) a postseizure postictal depression during which the patient is confused.
About 50 percent of grand mal seizures are preceded by an aura.
The petit mal (“little bad”) attack is a loss of awareness with no motor activity except
for blinking, turning the head, or rolling the eyes. Petit mal attacks are of brief duration,
seldom exceeding about 10 s. The typical EEG recording of a petit mal seizure
has a 3/s spike-and-wave pattern.
TREATMENT OF EPILEPSY
The treatment of choice for epilepsy is an anticonvulsant drug such as diphenylhydantoin
(DPH, Dilantin), phenobarbital, or one of several others (Rogawski & Loscher,
2004). These drugs are anesthetic agents when given in low doses, and patients are advised
not to drink alcohol. Although the mechanism by which these drugs act is uncertain,
they presumably inhibit the discharge of abnormal neurons by stabilizing the
neuronal membrane, especially in inhibitory neurons.
If medication fails to alleviate the seizure problem satisfactorily, surgery can be
performed to remove the focus of abnormal functioning in patients with focal
seizures. The abnormal tissue is localized by the surgeon both by EEG and cortical
stimulation (Chapter 9). It is then removed with the goal of eliminating the cause of
the seizures. Many patients show complete recovery and are seizure free, although
some must remain on anticonvulsants after the surgery to ensure that the seizures do
not return.
Multiple Sclerosis
Recall from Chapter 3 that, in multiple sclerosis (MS),myelin is damaged
and the functions of the neurons whose axons it encases are disrupted.
Multiple sclerosis is characterized by the loss of myelin,
largely in motor tracts but also in sensory nerves. The myelin sheath
and, in some cases, the axons are destroyed. Brain imaging with MRI,
as shown in Figure 15-7, allows areas of sclerosis (Greek for “hardness”)
to be identified in the brain and spinal cord.
Remissions and relapses are a striking feature of MS: in many
cases, early symptoms are initially followed by improvement. The
course varies, running from a few years to as long as 50 years. Paraplegia,
however, the classic feature of MS,may eventually confine the
affected person to bed.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 589
Lateral ventricles
Lesions
White matter
Plane of MRI section
Figure 15-7
Diagnosing MS Imaged by MRI,
discrete multiple sclerosis lesions appear
around the lateral ventricles and in the
white matter of the brain. Adapted from
Ciccarelli et al., 2000.
Automatism. Unconscious, repetitive,
stereotyped movement characteristic of
seizure.
Catatonic posture. Rigid or frozen pose
resulting from a psychomotor
disturbance.
Grand mal seizure. Characterized by
loss of consciousness and stereotyped
motor activity.
Postictal depression. Postseizure state
of confusion and reduced affect.
Petit mal seizure Of brief duration, a
seizure characterized by loss of awareness
with no motor activity except for blinking,
turning the head, or rolling the eyes.
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Worldwide, about 1 million people are afflicted with MS; women outnumber men
about two to one. Multiple sclerosis is most prevalent in northern Europe, somewhat
less prevalent in North America, and rare in Japan and in more southerly or tropical
countries. The overall incidence of of MS is 50 per 100,000 people, making it one of
the most common structural diseases of the nervous system.
The cause of MS is still not known. Proposed causes include bacterial infection, a
virus, environmental factors including pesticides, and an immune response of the central
nervous system. Often a number of cases will be seen in a single family, but there
is no clear evidence that MS is inherited or that it is transmitted from one person to
another.
ROLE OF THE IMMUNE SYSTEM IN MULTIPLE SCLEROSIS
The ability to discriminate between a foreign pathogen in the body and the body
itself is a central feature of the immune system. In autoimmune diseases such as
myasthenia gravis, the immune system makes antibodies to a person’s own body
(Chapter 4). Recent research has focused on the possible relation of the immune system
to MS.
As the genomes of various organisms have been sequenced in recent years, it has
become apparent that all biological organisms have many genes in common, and thus
the proteins found in different organisms are surprisingly similar. And here is the
problem for the human immune system: a foreign microbe may have proteins that are
very similar to the body’s own proteins. If the microbe and human have a common
gene sequence, the immune system can mistakenly attack itself, a process known as
horror autotoxicus. Many microbial protein sequences are homologous with structures
found in myelin, which leads to an attack against the microbe and a person’s own
myelin.
The work showing the important role of the immune system in MS has led to intense
research to develop new treatments (Steinman et al., 2002). One strategy is to
build up tolerance in the immune system by the injection of DNA encoding myelin
antigens as well as DNA encoding specific molecules that are in the cascade of steps
that leads to the death of myelin cells.
Neurodegenerative Disorders
Demographics such as those now developing in North America and Europe have
never been experienced by human societies. Since 1900, the percentage of older people
has been steadily increasing. In 1900, about 4 percent of the population had attained
65 years of age. By 2030, about 20 percent of the population will be older than
65—about 50 million in the United States alone. Dementias affect from 1 to 6 percent
of the population older than age 65 and from 10 to 20 percent older than age 80. It
has been estimated that, for every person diagnosed with dementia, several others
suffer undiagnosed cognitive impairments that affect their quality of life (Larrabee &
Crook, 1994).
Projections over the next 35 years estimate that between 10 and 20 million elderly
people in the United States will have mild to severe cognitive impairments.When this
projection is extended across the rest of the developed world, the social and economic
costs are truly staggering.Not every person who grows old also becomes depressed, forgetful,
or demented. Many people live to very old age and enjoy active, healthy, productive
lives. The question for most of us is how to ensure that we are in this latter
group; at present, however, there are depressingly few answers.
590 ! CHAPTER 15
Autoimmune disease. Illness resulting
from the immune system’s loss of the
ability to discrimininate between foreign
pathogens in the body and the body itself.
Dementia. Acquired and persistent
syndrome of intellectual impairment
characterized by memory and
other cognitive deficits and impairment
in social and occupational functioning.
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TYPES OF DEMENTIA
Dementia refers to an acquired and persistent syndrome of intellectual impairment.The
DSM-IV-TR defines the two essential diagnostic features of dementia as (1) memory and
other cognitive deficits and (2) impairment in social and occupational functioning.
Daniel Kaufer and Steven DeKosky (1999) divide dementias into two broad categories:
degenerative and nondegenerative (Table 15-8).
Nondegenerative dementias are a heterogeneous group of disorders with diverse
etiologies, including diseases of the vascular or endocrine systems, inflammation, nutritional
deficiency, and toxic conditions, as summarized in the right-hand column of
Table 15-8. In contrast,many degenerative dementias listed in the left-hand column are
presumed to have a degree of genetic transmission. Here we review two in detail,
Parkinson’s disease and Alzeimer’s disease. Both pathological processes are primarily
intrinsic to the nervous system and tend to affect certain neural systems selectively.
PARKINSON’S DISEASE
Parkinson’s disease is fairly common; estimates of its incidence vary from 0.1 percent
to 1.0 percent of the population, and the incidence rises sharply in old age. In view of
the increasingly aging population in western Europe and North America, the incidence
of Parkinson’s disease is certain to rise in the coming decades. As detailed in Chapter
5, Parkinsonism is also of interest for a number of other reasons:
Parkinson’s disease seems related to the degeneration of the substantia nigra and to
the loss of the neurotransmitter dopamine, which is produced there and released in the
striatum. The disease, therefore, is the source of an important insight into the role of
this brainstem nucleus and its dopamine in the control of movement.
Although Parkinson’s disease is described as a disease entity, symptoms vary enormously
among people, thus illustrating the complexity in understanding a behavioral
disorder. Parkinson’s disease has a well-defined set of cells that degenerate, yet the
symptoms are not the same in every sufferer.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 591
Degenerative and Nondegenerative Dementias
Degenerative Nondegenerative
Source: Adapted from “Diagnostic Classifications: Relationship to the Neurobiology of Dementia,” by D. I. Kaufer
and S. T. DeKosky, 1999, in The Neurobiology of Mental Illness (p. 642), edited by D. S. Charney, E. J. Nestler, and
B. S. Bunney, New York: Oxford University Press.
Vascular dementias (e.g., multi-infarct
dementia)
Infectious dementia (e.g., AIDS dementia)
Neurosyphillis
Posttraumatic dementia
Demyelinating dementia (e.g., multiple
sclerosis)
Toxic or metabolic disorders (e.g., vitamin
B12 and niacin deficiencies)
Chronic alcohol or drug abuse (e.g.,
Korsakoff’s syndrome)
Alzheimer’s disease
Extrapyramidal syndromes (e.g., progressive
supernuclear palsy)
Wilson’s disease
Huntington’s disease
Parkinson’s disease
Frontal temporal dementia
Corticobasal degeneration
Leukodystrophies (e.g.,
adrenoleukodystrophy)
Prion-related dementias (e.g., Creutzfeld-
Jakob disease)
Table 15-8
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Many symptoms of Parkinson’s disease strikingly resemble changes in motor activity
that take place as a consequence of aging. Thus the disease is a source of indirect insight
into the more general problems of neural changes in aging.
The symptoms of Parkinson’s disease begin insidiously, often with a tremor in one
hand and with slight stiffness in the distal parts of the limbs. Movements may then
become slower, the face becoming masklike with loss of eye blinking and poverty of
emotional expression. Thereafter the body may become stooped, and the gait becomes
a shuffle with the arms hanging motionless at the sides. Speech may become slow and
monotonous, and difficulty in swallowing may cause drooling.
Although the disease is progressive, the rate at which the symptoms worsen is variable,
and only rarely is progression so rapid that a person becomes disabled within 5
years; usually from 10 to 20 years elapse before symptoms cause incapacity. A most curious
aspect of Parkinson’s disease is its on-again–off-again quality: symptoms may appear
suddenly and disappear just as suddenly.
Partial remission may also occur in response to interesting or stimulating situations.
Recall from Chapter 5 that Oliver Sacks recounted an incident in which a stationary
Parkinson patient leaped from his wheelchair at the seaside and rushed into the breakers
to save a drowning man, only to fall back into his chair immediately afterward and
become inactive again. Although remission of some symptoms in activating situations
is common, remission is not usually as dramatic as this case.
The four major symptoms of Parkinson’s disease are tremor, rigidity, loss of spontaneous
movement (akinesia), and disturbances of posture.Each symptom may be manifest
in different body parts in different combinations. Because some of the symptoms entail
the appearance of abnormal behaviors (positive symptoms) and others the loss of normal
behaviors (negative symptoms),we consider the symptoms in these two major categories.
To review, positive symptoms are behaviors not seen in normal people or seen only
so rarely—and then in such special circumstances—that they can be considered abnormal.
Negative symptoms are marked not by any particular behavior but rather by the
absence of a behavior or by the inability to engage in an activity.
Positive Symptoms Because positive symptoms are common in Parkinson’s disease,
they are thought to be held in check, or inhibited, in normal people but released from
inhibition in the process of the disease. The most common positive symptoms are:
Tremor at rest. Tremor consists of alternating movements of the limbs when they
are at rest; these movements stop during voluntary movements or during sleep. The
tremors of the hands often have a “pill rolling’’ quality, as if a pill were being rolled between
the thumb and forefinger.
Muscular rigidity. Muscular rigidity consists of increased muscle tone simultaneously
in both extensor and flexor muscles. It is particularly evident when the limbs are
moved passively at a joint; movement is resisted, but, with sufficient force, the muscles
yield for a short distance and then resist movement again. Thus, complete passive flexion
or extension of a joint occurs in a series of steps, giving rise to the term cogwheel
rigidity. The rigidity may be severe enough to make all movements difficult, like moving
in slow motion but being unable to speed up the process.
Involuntary movements. These small movements or changes in posture, sometimes
referred to as akathesia or “cruel restlessness,” may be concurrent with general inactivity
to relieve tremor and sometimes to relieve stiffness but often for no apparent reason.
Other involuntary movements are distortions of posture, such as occur during
oculogyric crisis (involuntary turns of the head and eyes to one side), which last for periods
of minutes to hours.
592 ! CHAPTER 15
Akathesia. Small, involuntary
movements or changes in posture; motor
restlessness.
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Negative Symptoms After detailed analysis of negative symptoms, Jean Prudin Martin
(1967) divided patients severely affected with Parkinson’s disease into five groups:
1. Disorders of posture. These disorders include those of fixation and of equilibrium.
A disorder of fixation presents as an inability, or difficulty, in maintaining a part of
the body (head, limbs, and so forth) in its normal position in relation to other
parts. A person’s head may droop forward or a standing person may gradually
bend forward until he or she ends up on the knees.Disorders of equilibrium create
difficulties in standing or even sitting unsupported. In less severe cases, people may
have difficulty standing on one leg, or, if pushed lightly on the shoulders, they may
fall passively without taking corrective steps or attempting to catch themselves.
2. Disorders of righting. In these disorders, a person has difficulty in achieving a
standing position from a supine position. Many advanced patients have difficulty
even in rolling over.
3. Disorders of locomotion. Normal locomotion requires support of the body against
gravity, stepping, balancing while the weight of the body is transferred from one
limb to another, and pushing forward. Parkinson patients have difficulty initiating
stepping, and, when they do walk, they shuffle with short footsteps on a fairly wide
base of support because they have trouble maintaining equilibrium when shifting
weight from one limb to the other. Often, Parkinson patients who have begun to
walk demonstrate festination: they take faster and faster steps and end up running
forward.
4. Disturbances of speech. One of the symptoms most noticeable to relatives is the almost
complete absence of prosody in the speaker’s voice.
5. Akinesia. A poverty or slowness of movement may also manifest itself in a blankness
of facial expression or a lack of blinking, swinging of the arms when walking, spontaneous
speech, or normal movements of fidgeting. It is also manifested in difficulty
in making repetitive movements, such as tapping, even in the absence of rigidity.
People who sit motionless for hours show akinesia in its most striking manifestation.
Cognitive Symptoms Although Parkinson’s disease is usually thought of as a motor
disorder, changes in cognition occur as well. Psychological symptoms in Parkinson patients
are as variable as the motor symptoms. Nonetheless, a significant percentage of
patients show cognitive symptoms that mirror their motor symptoms.
Oliver Sacks, for example, reports the negative effects of Parkinsonism on cognitive
function: an impoverishment of feeling, libido, motive, and attention; people may
sit for hours, apparently lacking the will to begin or continue any activity. In our experience,
thinking seems generally to be slowed and is easily confused with dementia
because patients do not appear to be processing the content of conversations. In fact,
they are simply processing very slowly.
The cognitive slowing in Parkinson patients has some parallels to changes in
Alzheimer’s disease. Findings from postmortem studies show clear Alzheimer-like brain
abnormalities in most Parkinson patients, even if they did not have obvious signs of dementia.
We return to these parallels later.
Causes of Parkinsonism As stated in Chapter 5, the ultimate cause of Parkinson’s
disease is the loss of cells in the substantia nigra. This loss may be due to disease, such
as encephalitis or syphillis, to drugs such as MPTP (see “The Case of the Frozen Addict”
on page 171), or to unknown causes that are referred to as idiopathic. Idiopathic
causes may be familial or may be part of the aging process.
Idiopathic causes may also include environmental pollutants, insecticides, and
herbicides. Demographic studies of patient admission in the cities of Vancouver and
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 593
Festination. Tendency to engage in a
behavior, such as walking, at faster and
faster speeds.
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Helsinki show an increase in the incidence of patients getting the disease at ages
younger than 40. This finding has prompted the suggestion that water and air might
contain environmental toxins that work in a fashion similar to MPTP.
Treatment of Parkinson’s Disease No known cure for Parkinson’s disease exists,
and none will be in sight until the factors that produce the progressive deterioration of
the substantia nigra are known. Thus, treatment is symptomatic and directed toward
support and comfort. The major symptoms of Parkinsonism are influenced by psychological
factors, a person’s outcome being affected by how well he or she copes with
the disability.
As a result, patients should seek behaviorally oriented treatment early, including
counseling on the meaning of symptoms, the nature of the disease, and the potential
for most to lead long and productive lives. Physical therapy should consist of simple
measures such as heat and massage to alleviate painful muscle cramps and training and
exercise to cope with the debilitating changes in movement. Pharmacological treatment
has two main objectives:
1. to increase the activity in whatever dopamine synapses remain and
2. to suppress the activity in structures that show heightened activity in the absence
of adequate dopamine action.
L-Dopa, which is converted into dopamine in the brain, enhances effective dopamine
transmission, as do drugs such as amantadine, amphetamine, monoamine oxidase
inhibitors, and tricyclic antidpressants.Naturally occurring anticholinergic drugs,
such as atropine and scopolamine, and synthetic anticholinergics, such as benztropine
(Cogentin), and trihexyphenidyl (Artane), are used to block the cholinergic systems of
the brain that seem to show heightened activity in the absence of adequate dopamine
activity.
A drawback of drug therapies is that, as the disease progresses, they become less
effective and produce an increased incidence of side effects. Some drug treatments in
which dopamine receptors are directly stimulated have been reported to result in increased
sexuality and an increased incidence of compulsive gambling.
A number of treatments of Parkinson’s disease focus on treating its positive symptoms.
Two surgical treatments described earlier in the chapter are based on the idea
that an increase in the activity of globus pallidus neurons inhibits motor function. Lesioning
the internal part of the globus pallidis (GPi) has been found to reduce rigidity
and tremor. Hyperactivity of GPi neurons can also be reduced by electrically stimulating
the neurons, a neurosurgical treatment called deep brain stimulation (DBS), permanently
implanting a stimulating electrode in the GPi or an adjacent brain area, the
subthalamic nucleus. Patients carry a small electrical stimulator that they can turn on
to produce DBS and so reduce the symptoms of rigidity and tremor. These two treatments
may be used sequentially: when DBS becomes less effective as the disease progresses,
an GPi lesion may be produced.
A promising treatment is to try to increase the number of dopamine-producing
cells. The simplest way to do so is to transplant embryonic dopamine cells into the basal
ganglia and, in the 1980s and 1990s, this treatment was used to varying degrees of success.
A newer course of treatment proposes to increase the number of dopamine cells
either by transplanting stem cells that could then be induced to take a dopaminergic
phenotype or by stimulating the production of endogenous stem cells and their migration
to the basal ganglia.
The advantage of stem cells is that they do not have to be derived from embryonic
tissue but can come from a variety of sources including the person’s own bone mar-
594 ! CHAPTER 15
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row. Another source of dopamine cells is retinal endothelial cells that can be harvested
from neonatal tissue. The advantage of these cells is that a single retina can generate
enough cells to treat hundreds of patients.
All these treatments are highly experimental.At present, neonatal retinal cells have
probably been the most successful. Curiously, perhaps because this treatment is the
least controversial, the media have basically ignored it and have focused on the more
contentious issue of using embrological tissue. The retinas can be harvested from newborn
infants who die and, as noted, a single retina can generate cells for thousands of
patients, meaning that very few donors are necessary.
ANATOMICAL CORRELATES OF ALZHEIMER’S DISEASE
The most prevalent dementia is Alzheimer’s disease, which accounts for about 65 percent
of all dementias. At present the cause of Alzheimer’s disease is unknown. Given the
increasing population of elderly people and thus of Alzheimer’s disease, research is being
directed toward potential causes, including genetic predisposition, environmental toxins,
high levels of trace elements such as aluminum in the blood, an autoimmune response,
a slow-acting virus, and reduced blood flow to the cerebral hemispheres.
Until a decade ago, the only way to identify and to study Alzheimer’s disease was
to study postmortem pathology. This approach was less than ideal, however, because a
determination of which brain changes came early in the disease and which followed as
a result of the early changes was impossible. Nonetheless, it became clear that widespread
changes take place in the neocortex and limbic cortex and associated changes
take place in a number of neurotransmitter systems, none of which alone can be correlated
simply with Alzheimer’s clinical symptoms. Interestingly, most of the brainstem,
cerebellum, and spinal cord are relatively spared its major ravages.
The principal neuroanatomical change in Alzheimer’s disease is the emergence of
neuritic (amyloid) plaques, chiefly in the cerebral cortex (see “Alzheimer’s Disease” on
page 498). Increased plaque concentration in the cortex has been correlated with the
magnitude of cognitive deterioration. Neuritic plaques are generally considered nonspecific
phenomena in that they can be found in non-Alzheimer patients and in dementias
caused by other known events.
Another anatomical correlate of Alzheimer’s disease is neurofibrillary tangles—
paired helical filaments that are found in both the cerebral cortex and the hippocampus.
The posterior half of the hippocampus is affected more severely than the
anterior half. Light-microscopic examination has shown that the filaments have a double-
helical configuration. They have been described mainly in human tissue and have
also been observed in patients with Down’s syndrome, Parkinson’s disease, and other
dementias.
Finally, neocortical changes that correlate with Alzheimer’s disease are not uniform.
Although the cortex shrinks, or atrophies, losing as much as one-third of its volume
as the disease progresses, some areas are relatively spared. Figure 15-8 shows
lateral and medial views of the human brain; color stippling indicates the areas of degeneration.
The darker the stippling, the more severe the degeneration.
As is clearly shown in Figure 15-8A, the primary sensory and motor areas of the
cortex, especially the visual cortex and the sensory–motor cortex, are spared. The
frontal lobes are less affected than the posterior cortex, but the areas of most extensive
change are the posterior parietal areas, inferior temporal cortex, and limbic cortex. The
limbic system undergoes the most severe degenerative changes in Alzheimer’s disease,
and, of the limbic structures, the entorhinal cortex is affected earliest and most severely
(Figure 15-8B).
A number of investigators agree that the entorhinal cortex shows the clearest evidence
of cell loss. This loss has important implications for understanding some of the
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 595
(B) Limbic cortex
(A) Posterior parietal cortex
Inferior temporal cortex
Figure 15-8
Cortical Degeneration in Alzheimer’s
Disease Representative distribution
and severity of degeneration in an
average Alzheimer case shown in
(A) lateral and (B) medial views. The
darker the area, the more pronounced
the degeneration. Areas in white are
largely spared, with only basic changes
discernible. Adapted from Brun, 1983.
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disease symptoms. The entorhinal cortex is the major relay through
which information from the neocortex gets to the hippocampus and related
structures and is then sent back to the neocortex. Damage to the
entorhinal cortex is associated with memory loss. Given that memory
loss is an early and enduring symptom of Alzheimer’s disease, it is most
likely caused by the degenerative changes that take place in this area of
the cortex.
Many studies describe loss of cells in the cortices of Alzheimer patients,
but this finding is disputed. There seems to be a substantial reduction
in large neurons, but these cells may shrink rather than disappear.
The more widespread cause of cortical atrophy, however, appears to be a
loss of dendritic arborization.
In addition to a loss of cells are changes in the neurotransmitters of
the remaining cells. In the 1970s, researchers believed that a treatment for
Alzheimer’s disease could be found to parallel the L-dopa treatment of Parkinson’s disease,
and the prime candidate neurotransmitter was acetylcholine. Unfortunately, the
disease has proved to be far more complex, because other transmitters clearly are
changed as well.Noradrenaline, dopamine, and serotonin are reduced, as are the NMDA
and AMPA receptors for glutamate.
Are Parkinson’s and Alzheimer’s Aspects
of One Disease?
Striking similarities in the pathologies of Parkinson’s and Alzheimer’s diseases led
Donald Calne to ask whether these diseases are syndromes resulting from various neurodegenerative
processes in the brain (Calne & Mizuno, 2004). Their pathologies are
far more similar than was previously recognized.
One apparent difference that we have seen already is that all cases of Parkinson’s
disease have in common a loss of cells in the substania nigra. The Parkinsonian brain
suffers a larger loss, but the brains of Alzheimer patients also have nigral cell loss. There
are other anatomical correlates between the diseases.
The best studied of these correlates is the Lewy body, a circular fibrous structure
that forms within the cytoplasm of neurons and is thought to correspond to abnormal
neurofilament metabolism (Figure 15-9). Until recently, the Lewy body was believed
to be a hallmark of Parkinson’s disease, and it was most often found in the
brainstem in the region of the substantia nigra. It is now clear, however, that
Lewy bodies are found in several neurodegenerative disorders, including Alzheimer’s
disease. There are even reports of people with Alzheimer’s-like dementias
who do not have plaques and tangles but have extensive Lewy bodies in the
cortex.
Calne noted that, when investigators went to Guam at the end of the Second
World War to investigate a report of widespread dementia described as similar to
Alzheimer’s disease, they did indeed report a high incidence of Alzheimer’s disease.
Many years later, Calne and his colleagues, experts in Parkinson’s disease, examined
the same general group of people and found that they had Parkinson’s disease.
Calne noted that, if you look for Alzheimer symptoms in these people, you find them
and miss the Parkinson symptoms. And visa versa.
Indeed, as we age, all of us will show a loss of cells in the substantia nigra, but only
after we have lost about 60 percent of them will we start to show Parkinson symptoms.
From this perspective, we begin to understand Calne’s powerful argument and its important
implications for treating both syndromes.
596 ! CHAPTER 15
Midbrain Lewy body
Figure 15-9
Lewy Body Lewy bodies are
characteristic of Parkinson’s disease
and are found in the brains of patients
with other disorders as well. (Courtesy of
J. T. Stewart, MD, University of South Florida
College of Medicine.)
Lewy body. Circular fibrous structure,
found in several neurodegenerative
disorders, that forms within the cytoplasm
of neurons and is thought to result from
abnormal neurofilament metabolism.
Normal adult
pattern
Early
Alzheimer’s
disease
Advanced
Alzheimer’s
disease
Terminal
Alzheimer’s
disease
As their neurons degenerate, patients with
Alzheimer’s disease experience worsening
symptoms, including memory loss and
personality changes. Neurons drawn from
Golgi-stained sections in “Age-Related Changes in
the Human Forebrain,” by A. Scheibel, Neuroscience
Research Program Bulletin, 1982, 20, pp. 577–583.
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UNDERSTANDING AND TREATING
PSYCHIATRIC DISORDERS
The DSM-IV-TR summarizes a wide range of psychiatric disorders.We focus on three
general types that are the best studied and understood and are summarized in Table
15-9: psychosis, mood disorders, and anxiety disorders. Added together, the prevelances,
given in the middle column of the Table 15-9, show that psychiatric disorders
affect nearly half the U.S. population.
In Review .
We have considered five common neurological disorders: traumatic brain injury, stroke,
epilepsy, multiple sclerosis, and two neurodegenerative diseases. Each of us in our lifetimes
will likely know a person who has one of these disorders, and chances are that we
will know of an example of each disorder. The cause of traumatic brain injuries is obvious—
namely, a blow to the head—but the pathology is far more difficult to identify, even
with fancy imaging techniques. The pathology of the other neurological disorders is
equally elusive, the causes are poorly understood, and some disorders, such as Parkinson’s
and Alzheimer’s, may actually be syndromes of a single disease. Effective treatments must
wait until the causes are far better understood than they are today.
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 597
The Spectrum of Psychiatric Illness
Disorder Prevalence (%) Common Symptoms
Psychotic disorders
Schizophrenia 1.3 Characterized by delusions, hallucinations, disorganized speech, inappropriate or blunted
emotional responses, loss of motivation and cogntive effects
Mood disorders
Major depression 5.3 Episodes during which the patient feels sad or empty nearly every day; loses interest or pleasure
in hobbies and activities, experiences changes in appetite, weight, energy levels or sleeping
patterns; harbors thoughts of death or suicide
Dysthymia 1.6 Similar to major depression but the symptoms are less severe and more chronic (years). Also
includes low self-esteem, fatigue, and poor concentration
Bipolar 1.1 Episodes of abnormally elevated or irritable mood during which the person feels inflated selfesteem,
needs less sleep, talks more than usual; or engages excessively in pleasurable but unwise
activities. These manic periods alternate with depressive episodes.
Anxiety disorders
Generalized anxiety 5 Unrealistic, excessive and long-lasting worry, motor tension, restlessness, irritability, difficulty
sleeping
Panic disorder 3 Brief, recurrent, unexpected episodes of terror, sympathetic crises, shortness of breath
Post-traumatic stress 3 Recurrent episodes of fear triggered by reminders of a previous extremely stressful event
Social phobia 13 Aversion, fear, autonomic arousal in unfamiliar social settings
Specific phobias 11 Aversion, fear, autonomic arousal in specific situations (exposure to animals, blood, and so on)
Obsessive-compulsive 2 Recurrent obsessions and compulsions: obsessions are persistent, intrusive, inappropriate thoughts
that cause anxiety; compulsions are repetitive acts that are performed to reduce anxiety
Source: Adapted from Gross and Hen, 2004; Hyman, 2003.
Table 15-9
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Psychotic Disorders
Psychotic disorders are psychological disorders in which a person loses contact with reality,
experiencing irrational ideas and distorted perceptions. Although there are many
psychotic disorders (among which are schizophrenia, schizoaffective disorder, and
schizophreniform disorder), schizophrenia is the most common and best understood.
It has become clear in the past 25 years that the complexity of behavioral and neurobiological
factors that characterize schizophrenia make it especially difficult to diagnose
and classify. Understanding schizophrenia is an evolving process that is far from
complete.
DIAGNOSING SCHIZOPHRENIA
The DSM-IV-TR lists six diagnostic symptoms of schizophrenia:
1. delusions, or beliefs that distort reality;
2. hallucinations, or distorted perceptions, such as hearing voices;
3. disorganized speech, such as incoherent statements or senselessly rhyming talk;
4. disorganized behavior or excessive agitation;
5. the opposite extreme, catatonic behavior; and
6. negative symptoms, such as blunted emotions or loss of interest and drive, all characterized
by the absence of some normal response.
The DSM-IV-TR criteria for schizophrenia are subjective. They are more helpful in
clinical diagnoses than in relating schizophrenia to measurable brain abnormalities.
CLASSIFYING SCHIZOPHRENIA
Timothy Crow addressed this problem by looking for a relation between brain abnormalities
and specific schizophrenia symptoms. He proposed two distinct syndromes,
which he called type I and type II (Crow, 1980, 1990).
Type I schizophrenia is characterized predominantly by positive symptoms, those
that manifest behavioral excesses, such as hallucinations and agitated movements. Type
1 schizophrenia is likely due to a dopaminergic dysfunction. It is also associated with
acute onset, good prognosis, and a favorable response to neuroleptics (antipsychotic
drugs; see Chapter 7).
Type II schizophrenia, in contrast, is characterized by negative symptoms, those
that entail behavioral deficits. Type II schizophrenia is associated with chronic affliction,
poor prognosis, poor response to neuroleptics, cognitive impairments, enlarged
ventricles, and cortical atrophy, particularly in the frontal cortex (see Figure 15-4).
Crow’s analysis had a major effect on clinical thinking about schizophrenia. Between
20 percent and 30 percent of patients, however, show a pattern of mixed type I and type
II symptoms. The types may actually represent points along a continuum of biological
and behavioral manifestations of schizophrenia.
NEUROANATOMICAL CORRELATES OF SCHIZOPHRENIA
Another approach to investigating schizophrenia is to deemphasize typing and to focus
instead on individual psychotic symptoms.Alan Breier (1999) stated that findings from
a growing number of brain-imaging studies suggest a neuroanatomical basis for some
diagnostic symptoms described by the DSM. For example, researchers found abnormalities
in the auditory regions of the temporal lobe and in Broca’s area among patients
with auditory hallucinations (McGuire, Shah, & Murray, 1993).
598 ! CHAPTER 15
Type I schizophrenia. Characterized
predominantly by positive symptoms
(behavioral excesses, such as
hallucinations and agitated movements);
likely due to a dopaminergic dysfunction
and associated with acute onset, good
prognosis, and a favorable response to
neuroleptics.
Type II schizophrenia. Characterized
by negative symptoms (behavioral
deficits) and associated with chronic
affliction, poor prognosis, poor response
to neuroleptics, cognitive impairments,
enlarged ventricles, and cortical atrophy,
particularly in the frontal cortex
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Similarly, structural abnormalities in Wernicke’s area are often found among patients
with thought disorders (Shenton et al., 1992). The schizophrenic brain also generally
has large ventricles and thinner cortex in the medial temporal regions, and the
dendritic fields of cells in the dorsal prefrontal regions and hippocampus are abnormal
(Cho Gilbert, & Lewis, 2004), as are those in the entorhinal cortex (Arnold, Rushinsky,
& Han, 1997). These regions participate in various forms of memory. Deficits in verbal
and spatial memory among people with schizophrenia will quite possibly turn out
to be correlated with these medial temporal abnormalities.
Another correlation is frequently seen in schizophrenia between an abnormally
low blood flow in the dorsolateral prefrontal cortex and deficits in executive functions,
such as those measured by the Wisconsin Card Sorting Test (for a review, see
Berman & Weinberger, 1999). Interestingly, when Daniel Weinberger and Barbara
Lipska (1995) studied pairs of identical twins in which only one twin had been diagnosed
as having schizophrenia, they found that the twin with schizophrenia always
had a lower blood flow in the prefrontal cortex while taking this card-sorting test (see
Figure 15-3).
NEUROCHEMICAL CORRELATES OF SCHIZOPHRENIA
Neuroscientists also consider the neurochemical correlates of brain–behavior relations
in schizophrenia. As discussed in Chapter 7, dopamine abnormalities were the
first to be linked to schizophrenia, and the fact that most neuroleptic drugs act on the
dopamine synapse was taken as evidence that schizophrenia is a disease of ventral
tegmental dopamine system. Similarly, drugs that enhance dopaminergic activity, such
as amphetamine, can produce psychotic symptoms reminiscent of schizophrenia.
The dopamine theory of schizophrenia now appears to be too simple, however, because
many other neurochemical abnormalities, summarized in Table 15-10, also have
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 599
Hippocampus
Organized (normal) pyramidal neurons
(A)
Disorganized (schizophrenic) pyramidal neurons
(B) Rather than the consistently parallel
orientation of hippocampal neurons
characteristic of normal brains
(A), hippocampal neurons in the
schizophrenic brain have a haphazard
organization (B). Adapted from “A
Neurohistologic Correlate of Schizophrenia,”
by J. A. Kovelman and A. B. Scheibel, 1984,
Biological Psychiatry, 19, p. 1613.
Biochemical Changes Associated with Schizophrenia
Decreased dopamine metabolites in cerebrospinal fluid
Increased striatal D2 receptors
Decreased expression of D3 and D4 mRNA in specific cortical regions
Decreased cortical glutamate
Increased cortical glutamate receptors
Decreased glutamate uptake sites in cingulate cortex
Decreased mRNA for the synthesis of GABA in prefrontal cortex
Increased GABAA-binding sites in cingulate cortex
Source: Adapted from “The Neurochemistry of Schizophrenia,” by W. Byne, E. Kemegther, L. Jones, V.
Harouthunian, and K. L. Davis, 1999, in The Neurobiology of Mental Illness (p. 242), edited by D. S. Charney, E. J.
Nestler, and B. S. Bunney, New York: Oxford University Press.
Table 15-10
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been associated with schizophrenia. In particular are abnormalities in dopamine and
dopamine receptors, glutamate and glutamate receptors, and GABA and GABA binding
sites. Considerable variability exists among patients in the extent of each of these
abnormalities, however. How these neurochemical variations might relate to the presence
or absence of specific symptoms is not yet known.
To summarize, schizophrenia is a complex disorder associated with both positive
and negative symptoms, abnormalities in brain structure and metabolism (especially
in the prefrontal and temporal cortex), and neurochemical abnormalities in regard to
dopamine, glutamate, and GABA. Given the complexity of all these behavioral and
neurobiological factors, it is not surprising that schizophrenia is so difficult to characterize
and to treat.
Mood Disorders
In the past 50 years, researchers have debated whether mood disorders are psychological
or biological in origin. Now, in those with genetic predispositions to stress, environmental
factors seem likely to act on the brain to produce biological changes related
to people’s moods and emotions. Although the precise nature of a genetic reactivity to
stress is not fully understood, several genes have been implicated (Sanders, Detera-
Wadleigh, & Gershon, 1999).
The DSM-IV-TR identifies a continuum of mood disorders, but the ones of principal
interest here—depression and mania—represent the extremes of affect (see Table
15-9). The main symptoms of major depression are prolonged feelings of worthlessness
and guilt, disruption of normal eating habits, sleep disturbances, a general slowing
of behavior, and frequent thoughts of suicide (Chapter 7).
Mania, the opposite affective extreme from depression, is characterized by excessive
euphoria. The affected person often formulates grandiose plans and behaves in an uncontrollably
hyperactive way. Periods of mania often change, sometimes abruptly, into
states of depression and back again to mania. This condition is called bipolar disorder.
Little is known about the neurobiology of bipolar disorder.
Our emphasis here is on extending your knowledge about depression. Findings
from clinical studies suggest that monoamine systems, particularly both the norepinephrine
and the serotonin systems, have roles in depression. Many monoamine
theories of depression have been proposed (review Chapter 7). To date, however, no
unifying theory fully explains either the development of depression in otherwise normal
people or how antidepressant medications treat it.
NEUROBIOLOGY OF DEPRESSION
Neuroscientists have known for more than 30 years that antidepressant drugs acutely
increase the synaptic levels of norepinephrine and serotonin. This finding led to the idea
that depression results from a decrease in the availability of one or both neurotransmitters.
Lowering their levels in normal subjects does not produce depression, however.
Recall, too, that antidepressant medications increase the level of norepinephrine and
serotonin within days, but it takes weeks for drugs to start relieving depression.
Various explanations for these results have been suggested, none completely satisfactory.
Ronald Duman (2004) reviewed evidence to suggest that antidepressants act,
at least in part, on signaling pathways, such as on cAMP, in the postsynaptic cell. Neurotrophic
factors appear to affect the action of antidepressants and, furthermore, neurotrophic
factors may underlie the neurobiology of depression. Investigators know, for
example, that brain-derived neurotrophic factor is down-regulated by stress and upregulated
by antidepressant medication (Chapter 13).
600 ! CHAPTER 15
Mania. Disordered mental state
characterized by excessive euphoria.
Bipolar disorder. Mood disorder
characterized by alternating periods of
depression and mania.
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Given that BDNF acts to enhance the growth and survival of cortical neurons and
synapses, BDNF dysfunction may adversely affect noreprinephrine and serotonin systems
through the loss of either neurons or synapses. Antidepressant medication may
increase the release of BDNF through its actions on cAMP signal transduction. The key
point here is that the cause is most likely not just a simple decrease in transmitter levels.
Rather, explaining both the biochemical abnormalities in depression and the actions
of antidepressants is likely far more complex than it seemed a generation ago.
MOOD AND REACTIVITY TO STRESS
A significant psychological factor in understanding depression is reactivity to stress.
When we are stressed, the hypothalamic-pituitary-adrenal system (HPA axis) is stimulated
to produce stress hormones—steroids such as cortisol (hydrocortisone).
Monoamines modulate the secretion of hormones by the HPA axis, as illustrated in
Figure 15-10.
The best-established abnormality in the HPA-axis modulation is an oversecretion
of cortisol from the adrenal gland. As explained in Chapter 7, normally, when you are
stressed, the hypothalamus secretes corticotropin-releasing hormone,which stimulates
the pituitary to produce adrenocorticotropic hormone (ACTH). The ACTH circulates
through the blood and stimulates the adrenal medulla to produce cortisol.
The hypothalamic neurons that begin this cascade are regulated by norepinephrine
neurons in the locus coeruleus. If the cortisol release is too large, the norepinephrine
neurons fail to regulate the cortisol. High levels of cortisol are bad for neurons,
and chronic increases lead to the death of neurons in the hippocampus.
Moreover, Charles Nemeroff (2004) showed that, during critical periods in early
childhood, abuse or other severe environmental stress can permanently disrupt the
reactivity of the HPA axis. Chronic stress can lead to the oversecretion of cortisol, an
imbalance associated with depression in adulthood.Nemeroff found, for example, that
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 601
HPA axis. Hypothalamic-pituitaryadrenal
circuit that controls the
production and release of hormones
related to stress.
Stress
ACTH
(C)–
Hypothalamus
Deactivation
feedback loop
Adrenal
gland
Kidney
Cortisol
In depression this
shutdown fails,
producing chronic
activation, which
is experienced as
chronic stress.
Corticotrophinreleasing
homone
Anterior
pituitary

Hypothalamus
Locus coeruleus
(A)–
Raphé nuclei
(B)–
Figure 15-10
HPA axis (A) In this medial view of
the stress activating system, the locus
coeruleus contains the cell bodies
of norepinephrine neurons, the
hypothalamus contains corticotrophinreleasing
hormone, and dopamine cell
bodies reside in the ventral tegmentum.
(B) Cell bodies of the serotonergic
activating system emanate from the
Raphé nuclei. (C) When activated, the
HPA system affects mood, thinking, and,
indirectly, the secretion of cortisol by the
adrenal glands. HPA deactivation begins
when cortisol binds to hypothalamic
receptors
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45 percent of adults with depression lasting 2 years or more had experienced abuse,
neglect, or parental loss as children.
Fluoxetine (Prozac), a major drug for treating depression, is an SSRI that effectively
increases the amount of serotonin in the cortex (Chapter 7). But independent of serotonin
production, fluoxetine stimulates both BDNF production and neurogenesis in
the hippocampus, resulting in a net increase in the number of granule cells (see “Antidepressant
Action in Neurogenesis”).
To summarize, the fact that noreprinephrine- and serotonin-activating systems are
so diffusely distributed makes relating depression to a single brain structure impossible.
Findings from neuroimaging studies show that depression is accompanied by an increase
in blood flow and glucose metabolism in the orbital frontal cortex, the anterior
602 ! CHAPTER 15
Antidepressant Action in Neurogenesis
Focus on New Research
A puzzle in treating depression is that, even though there is
an almost immediate increase in monoamines in the brains of
people who begin taking antidepressant drugs, patients typically
must wait from 3 to 4 weeks for the medication to take
effect. If low levels of monoamines cause depression, then
why does it take so long to see and feel improvement? One
explanation is that the increased monoamine levels initiate a
slow reparative process in their target areas in the brain.
In fact, findings from postmortem studies of the brains of
depressed people show cell loss in the prefrontal cortex and
hippocampus, and some of this loss may be reversed by the
antidepressants’ actions. Furthermore, exposure to chronic
stress can cause cell death and dendritic shrinkage in the hippocampus,
changes that likely result from high levels of cortisol.
The possibility arises, therefore, that antidepressant
drugs act to reverse cell loss, at least in the hippocampus. In
fact, there is good evidence that fluoxetine (Prozac) and other
SSRIs stimulate neurogenesis in the hippocampi of rats and
mice.
Luca Santarelli and colleagues (2003) conducted an experiment
to test whether antidepressants are capable of reversing
the behavioral symptoms when neurogenesis is
prevented in depressed animals. They used a mouse bred
with a genetic knockout manipulation that omitted a specific
serotonin receptor (5-HT-1A). This receptor is thought to be
stimulated by antidepressants such as fluoxetine.
The mice were tested in two behavioral procedures,
including one that the investigators proposed as a model of
depression. In this test, animals exposed to chronic unpredictable
stress develop a general deterioration in the state
of their fur coat and this deterioration can be reversed by
chronic, but not acute, treatment with antidepressants.
Santarelli’s team hypothesized that, if the action of fluoxetine
on depression was to increase neurogenesis in the
hippocampus, then mice without the necessary 5-HT-1A receptor
would not respond to the drug treatment. In contrast,
those animals with the serotonin receptor would show both
a reversal in cell loss in the hippocampus and in the associated
behavioral changes, which is exactly what the researchers
found. Importantly, the effect of the drug was not
seen after only 5 days of drug treatment, but it was seen after
11 or 28 days of treatment.
Santarrelli and his team concluded that the hippocampus
has a role in mood regulation and that interferring with
hippocampal neurogenesis impairs this mood regulation.
They proposed that antidepressants act, at least in part, to
increase neurogenesis and thus relieve the impairment in
hippocampal mood regulation. It is important to note that
humans with hippocampal damage are not typically depressed,
and so the way in which neurogenesis in the hippocampus
might relieve depression remains puz zling.
This study demonstrates how environmental factors such
as chronic stress may alter the human brain’s homeostatic regulator.
Santarelli’s animal model further explains how a class
of drugs (in this case, antidepressants) act at the cellular level
to reverse both anatomical and behavioral symptoms.
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cingulate cortex, and the amygdala. This elevated blood flow drops as the symptoms of
depression remit when a patient takes antidepressant medication (Drevets, Kishore, &
Krishman, 2004). The participation of these brain structures in affect should not be surprising,
given their role in emotional behavior (Chapter 11).
Anxiety Disorders
We all experience anxiety at some time, usually acutely as a response to a stressful stimulus
or, less commonly, as a chronic reactivity, an increased anxiety response, even to
seemingly minor stressors. Anxiety reactions certainly are not pathological and are
likely an evolutionary adaptation by which organisms cope with adverse conditions.
But anxiety can become pathological to the point of making life miserable.
As you discovered in Chapter 11, anxiety disorders are among the most common.
The DSM-IV lists six classes of anxiety disorders, which are summarized in Table 15-
9. Together, the six disorders affect more than 20 percent of the U.S. population at some
point in their lifetimes with an annual estimated cost of about $44 billion (Gross &
Hen, 2004).
Imaging studies of people with anxiety disorders record increased baseline activity
in the cingulate cortex and parahippocampal gyrus and an enhanced response to
anxiety-provoking stimuli in the amygdala and prefrontal cortex. The likely culprit
is excessive excitatory neurotransmission in the anterior cingulate cortex, prefrontal
cortex, amygdala, and parahippocampal region. Researchers hypothesize that, because
drugs that enhance the inhibitory transmitter GABA are particularly effective in reducing
anxiety, excessive excitatory neurotransmission may enhance anxiety. But what
is the cause?
In the past decade, considerable interest has developed in investigating why some
people show a pathological level of anxiety to stimuli to which others have a much-attenuated
response. One hypothesis, just covered in the section on depression, is that
stressful experiences early in life increase a person’s susceptibility to a variety of behavioral
abnormalities, especially anxiety disorders. Findings from studies on laboratory
animals confirm that early experience can alter the stress response in adulthood.
Michael Meaney and his colleagues (e.g.,Weaver et al., 2004) demonstrated a range
of maternal licking-and-grooming behavior among rat mothers. Pups raised by mothers
that display low levels of licking and grooming show more anxiety-related behaviors,
including an enhanced corticosterone response in response to mild stressors, than
do pups raised by mothers displaying high levels of licking and grooming.
What is particularly intriguing in these studies is that rat pups raised by low or
high lickers and groomers themselves show the same behavior toward their own infants.
This link is not a direct genetic one, however, because pups raised by adoptive
mothers show the behaviors of their adoptive mothers rather than their biological
mothers.
Meaney’s group showed that the licking-and-grooming behaviors alter the expression
of certain genes, thus showing that early experiences can alter the phenotype.
More exciting, the researchers have reversed the adverse effects of early experience with
chemical treatments. This promising line of inquiry will likely lead to new forms of
treatment for anxiety disorders in coming years.
Although anxiety disorders used to be treated primarily with benzodiazepines such
as Valium, now they are effectively treated with SSRIs such as Prozac, Paxil, Celexa, and
Zoloft. Antidepressant drugs do not act immediately, however, suggesting that SSRI
treatment must stimulate some gradual type of change in brain structure, much as in
the actions of these drugs in treating depression.
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Finally, simply giving medications does not give people the coping skills that they
may need to get better, as stated earlier. This statement is especially true for anxiety
disorders. The treatment of obsessive-compulsive disorders in particular requires an
integrated approach, including both medications and cognitive-behavior therapy
(CBT). This therapy focuses on challenging the reality of the patients’ obsessions
and the behavioral necessity for their compulsions. The most effective behavioral
therapies expose and reexpose the patients to their fears. For example, treating a
fear of germs requires that the patient be exposed repeatedly to potentially germy environments,
such as public washrooms, until the discomfort abates (Abramowitz,
1998).
IS MISBEHAVIOR ALWAYS BAD?
You know the movie plot in which a person has some sort of blow to the head and becomes
a different (and better) person.You might wonder whether pathological changes
in the brain and behavior sometimes lead to improvement. A report by Jim Giles
(2004) on Tommy McHugh’s case is thought provoking.
McHugh, a heroin addict, had committed multiple serious crimes and had spent a
great deal of time in jail. He suffered a cerebral hemorrhage (bleeding into the brain)
from an aneurysm. His bleeding was repaired surgically by placing a metal clip on the
leaking artery. After he recovered from the injury,McHugh showed a dramatic change
in personality, took up painting, which he had never done before, and has become a
successful artist. His life of crime is now only for the record books.
His injury-induced brain changes appear to have been beneficial. The exact nature
of McHugh’s brain injury is not easy to identify, because the metal clip in his brain precludes
the use of MRI. Aspects of his cognitive behavior suggest that he may have
frontal-lobe damage.
Bruce Miller has studied a larger group of 12 patients who, like Tommy McHugh,
have frontal or temporal injury or both. All developed new musical or artistic talents
after their injuries (Miller et al., 2000). Miller speculates that loss of function in one
brain area sometimes can release new functions elsewhere.
In Review .
Our knowledge of psychiatric disorders such as psychosis, mood disorders, and anxiety
disorders is best viewed as work in progress. Significant progress has been made in understanding
the neurobiology of these disorders. Schizophrenia is correlated with abnormalities
in dopamine, GABA, and glutamate systems. Structural abnormalities and low
blood-glucose utilization are observed in both the prefrontal cortex and the temporal cortex.
Treatments emphasize normalizing the dopaminergic abnormalties. In contrast, the
monoamine systems are abnormal in mood disorders, particularly in signal transduction
in postsynaptic cells. And, in depression, abnormally high levels of blood flow and glucose
utilization show up in the prefrontal and anterior cingulate cortex and in the amygdala.
Antidepressant treatments aim largely at normalizing the monoaminergic systems,
which in turn normalizes glucose utilization. Anxiety disorders are likely related to GABA
systems and abnormally high levels of blood flow in the cingulate cortex, amygdala, and
parahippocampal cortex. Treatments are aimed at reversing the GABAergic abnormalities
and helping people learn to modify their behaviors.
604 ! CHAPTER 15
Cognitive-behavior therapy (CBT)
Treatment that challenges the reality of
patients’ obsessions and the behavioral
necessity for their compulsions.
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The general idea that manipulating the brain might be beneficial is clearly a slippery
slope. The idea behind psychosurgery was based on this general idea (Chapter 11).
Today, it might be possible to influence brain function more scientifically through a
strategy loosely described as neurocognitive enhancement. The general idea is that, by
using our knowledge of pharmacology, brain plasticity, brain stimulation, neurogenetics,
and so on, it will one day be possible to manipulate brain functioning.
Many people already use drugs to alter brain function. But what about treatments
such as genetic manipulation? In the studies undertaken by Michael Meaney and his
collaborators, they were able to show that specific behavioral manipulations can alter
the expression of genes in rats. Serious moral and ethical issues certainly need discussion
before neuroscientists begin to offer routes to neurocogntive enhancement. (See
reviews of these issues by Caplan, 2003, and Farah et al., 2004).
SUMMARY
What are the prospects for creating a unified theory of the bain and behavior? Freud’s
theories have been out of favor in behavioral neuroscience for about 50 years, but modern
neuroimaging studies are reviving a Freudian-type theory of the self, a theory more
in keeping with current scientific knowledge about brain organization and function.
As a new, unifying model of the self develops, researchers and practitioners may begin
to identify the neural basis of diseases now labeled as “mental” or “psychiatric.”
What research methods do neuroscientists use to investigate the neurobiology of behavioral
disorders? Most behavioral disorders have multiple causes—genetic, biochemical,
anatomical, and social–environmental variables—all interacting. Research methods directed
toward these causes include family studies designed to find a genetic abnormality
that might be corrected, biochemical anomolies that might be reversed by drug or
hormone therapy, anatomical pathologies that might account for behavioral changes,
and social–environmental variables. Investigators rely increasingly on neuroimaging
(MRI, PET, TMS, ERP) to examine brain–behavior relations in vivo in normal subjects
as well as in those having disorders. Interest is growing in the use of more-refined
measurements of behavior, especially cognitive behavior, to better understand behavioral
symptoms.
How are disorders classified? Disorders can be classified according either to presumed
etiology (i.e., cause), to symptomatology, or to pathology. The primary etiological classification,
neurological versus psychiatric, is artificial, because it presupposes that two
classifications accommodate all types of disorders. In fact, as more is learned about etiology,
more disorders fall into the neurological category. The symptomatological classification
requires a checklist, such as the DSM-IV. The problem in such diagnosis is
that symptoms of psychiatric disorders overlap. The checklist of likely symptoms for
disorders is thus open to interpretation. Symptoms may appear more or less prominent,
depending on the perceptions of the classifier. The pathological classification of
behavioral disorders may be possible with MRI or other scans but often requires postmortem
examination. In either event, it is becoming clear that disorders have more
overlap in pathology than was previously recognized.
How are general treatment categories deployed to combat disorders of brain and behavior?
The treatment of behavioral disorders is usually tied to the presumed causes. If
a disorder is presumed to be primarily one of biochemical imbalance, such as depression,
the treatment is likely to be pharmacological. If the disorder has a suspected
anatomical cause, the treatment may include the removal of pathological tissue (e.g.,
epilepsy) or the use of implanted electrodes to activate underactive regions (e.g.,
WHAT HAPPENS WHEN THE BRAIN MISBEHAVES? ! 605
Neurocognitive enhancement.
Brain-function enhancement by
pharmacological, physiological, or
surgical manipulation.
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Parkinson’s disease, stroke). Brain activation with TMS is promising and noninvasive.
Many disorders, however, require medical treatment concurrent with behavioral therapy,
including physiotherapy or cognitive rehabilitation for stroke or trauma and behavioral
or cognitive therapies for anxiety disorders.
What is the neurological plague of the twenty-first century? The aging population of
the Western world will increase the number of people with hidden diseases of behavior,
especially the neurodegenerative disorders and stroke. Like other plagues in human
history, this one will affect not only the person who has the disease but also the caregivers.
About half of the caregivers for people with disorders linked to aging will seek
psychiatric care themselves.
Can brain dysfunction or alteration ever lead to positive outcomes? The logic of psychosurgery
is that, by altering brain organization, it might be possible to influence abnormal
behavior. The history of psychosurgery has not been a good one, but the
general principle could be applied to genetic manipulations, transplants, and brain
stimulation. There is also evidence that, in some cases, people with abnormal behaviors
may inadvertently benefit from neurological disease, although this outcome is certainly
not common.
KEY TERMS
REVIEW QUESTIONS
1. What are the difficulties in developing a unifying theory of the neurobiology of
abnormal behavior?
2. What are the causes of abnormal behavior?
3. What are the treatments for abnormal behavior?
4. What are the methods of studying brain and behavior?
5. In what sense is behavioral therapy a biological intervention?
FOR FURTHER THOUGHT
1. What type of studies will be required to establish the basis of mental disorders
and their treatments?
2. Why would abnormalities in the anterior cingulate and prefrontal cortex
produce so many different behavioral syndromes?
akathesia, p. 592
autoimmune disease,
p. 590
automatism, p. 589
behavioral therapy, p. 583
bipolar disorder, p. 600
catatonic posture, p. 589
cognitive-behavior therapy
(CBT), p. 604
cognitive therapy, p. 583
deep brain stimulation
(DBS), p. 579
dementia, p. 590
diaschisis, p. 587
DSM-IV-TR, p. 577
festination, p. 593
focal seizue, p. 588
grand mal seizure, p. 589
HPA axis, p. 601
idiopathic seizure, p. 587
ischemia, p. 586
Lewy body, p. 596
magnetic resonance
spectroscopy (MRS),
p. 586
mania, p. 600
neurocognitive
enhancement, p. 605
neuroprotectant, p. 587
petit mal seizure, p. 589
phenylketonuria (PKU),
p. 573
postictal depression, p. 589
psychotherapy, p. 584
symptomatic seizure, p. 587
tardive dyskinesia, p. 582
type I schizophrenia, p. 598
type II schizophrenia,
p. 598
606 ! CHAPTER 15
neuroscience interact ive
Many resources are available for
expanding your learning on-line:
www.worthpublishers.com/kolb/
chapter15
Try some self-tests to reinforce your
mastery of the material. Look at some
of the news updates on current research
on the brain. You’ll also be able to link
to other sites to reinforce what you’ve
learned.
Review the major concepts and
anatomical fundamentals in the
modules on the Central Nervous
System and Neural Communication
on the CD.
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RECOMMENDED READING
Barondes, S. M. (1993).Molecules and mental illness. New York: Scientific American Library.
Like the other books in the Scientific American Library, this one is beautifully written
and illustrated and is easily accessible. It provides a good general discussion of the
neurobiology of mental disorders.
Charney, D. S., & Nestler, E. J. (Eds.). (2004). The neurobiology of mental illness (2nd ed.).
New York: Oxford University Press. This is a serious book for those interested in the
latest information on the neurobiology of mental illness. Coverage includes the entire
spectrum of mental disorders with thorough reference lists and clear discussions.
Sacks, O. (1998). The man who mistook his wife for a hat: And other clinical tales. New York:
Touchstone. This collection of short essays provides interesting reading about some
strange relations between brain and behavior. Sacks is an excellent writer, and his
accounts are not only entertaining but thought provoking as well.
Solms, M., & Turnbull, O. (2002). The brain and the inner world. New York: Other
Press/Karnac Books. An introduction to the issues concerning the organization of the
mind and the brain.
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Throughout this book, we examined the nervous system with a focus on function,
on how our behavior and our brains interact. We began with Fred
Linge, who met the challenge of brain trauma sustained in a car accident by
learning to compensate for his changed abilities. The brain injuries suffered by Tan,
D. B., Roger, Donna, and other patients proved to be sources of insight into brain
function.
We met Alex the parrot, Kamala the elephant, puffins, sea bears, butterflies, sea
snails, fruit flies, and nematodes whose behavior also proved to be a source of insight
into brain function. We examined car engines, robots, and prehistoric flutes. Each
teaches a different lesson about the organization and functioning of the brain.
As we reflect on the many topics that we have covered, an important question
emerges: What basic concepts about the brain does all this information suggest? To
answer this question, we retrace our path from brain to behavior all the way back to
Chapter 2, to revisit the principles of nervous system function set out there.
You have seen that these big ideas apply equally at the micro and macro levels of
nervous system neurobiology, as well as to the broader picture of behavior that
emerges. In fact, however, most of the themes that have been introduced span more
than a single chapter in this book. Our goal here is to bind those themes together to
produce a set of key concepts about brain function and its links to behavior. The real
task is to learn how the brain produces behavior, including consciousness.
Neuroscience in an
Evolutionary Context
Revisiting the Principles of
Nervous System Function
Principle 1: Information-Processing Sequence in
the Brain Is ”In ! Integrate ! Out“
Principle 2: Sensory and Motor Functions
Throughout the Nervous System Are
Separated
Principle 3: Inputs and Outputs to the Brain
Are Crossed
Principle 4: Brain Anatomy and Function
Display Both Symmetry and Asymmetry
Principle 5: The Nervous System Works Through
Excitation and Inhibition
Principle 6: The Nervous System Functions on
Multiple Levels
Principle 7: Brain Components Operate Both
Parallelly and Hierarchically
Principle 8: Functions in the Brain Are Both
Localized in Specific Regions and Distributed
Neuroscience in the
Twenty-first Century
608 !
Epilogue
What Have We Learned and
What Is Its Value?
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WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 609
NEUROSCIENCE IN AN EVOLUTIONARY CONTEXT
Evolution results from the complex interplay of biology and environment, of genes and
experience. This ongoing interplay influences how humans and other animals behave
and learn from earliest infancy through old age. Experience can influence the messages
that genes produce, and genes, in turn, can influence an organism’s environment and
experience.
Our bodies and our behaviors stem in part from the activity of the 20,000 or so genes
that we inherit from our parents. Each gene encodes a protein, and each protein can be
modified or combined with one or many others to produce the hundreds of thousands
of molecules that build our brains. Predictable developmental stages are initiated by this
genetic code, but the details of development can be influenced by chance, by experience,
and by the environment (Figure E-1).
Experience does not just mean events in the outside world. It encompasses the
internal environment, too: the action of hormones and other neurochemicals, the
progress of a disease or recovery from an injury, and reactions to stress. Internal experience
includes our own thoughts (Chapter 14) and dreams (Chapter 12). Both
processes result from changes in our brains, and they cause neural changes as well.
The dance of genetic and experiential influences continues throughout our lives just
as it does in the continuing evolution of our species. Experiences can turn the genes in
neurons on, and the way in which genes are turned on influences experience. The influence
of genes and experience is not simply to form neurons and place them in
appropriate relations with one another but also to eliminate excess or faulty neurons and
connections, analogously to the sculpting of a statue from an unshaped block of marble.
REVISITING THE PRINCIPLES OF NERVOUS
SYSTEM FUNCTION
Determining the relative contributions that genes and environment make to the brain and
behavior has so far eluded science. But watching their interplay suggests general principles,
summarized in Table E-1, that form the basis for many discussions throughout
Cortical columns
from a normal cat
Cortical columns from a cat
deprived of vision in one eye
Infant
Adolescent
Adult
L R L R L L R L R L
Cats develop cortical
columns for ocular
dominance.
Genetics determines
the infant’s pattern of
neuronal growth…
…but, in normal cats,
experience causes the
development of discrete,
equal-width columns.
A cat deprived of vision in one eye
early in development develops
columns of unequal size.
Figure E-1
Critical Experience As detailed in
Chapter 6, beginning at a critical period
in its development, a kitten was deprived
of vision in its right eye. Whereas the
pattern of neural growth, determined by
genetic inheritance, is normal in the left
eye, the cortical dominance columns in
the right eye are abnormal, showing the
effect of experience.
Block of stone
Carving
Finished brain
In the first months of life, our brains
overproduce neurons and connections and
then prune away unnecessary neurons and
incorrect connections, analogously to a
sculptor chiseling a statue from a block of
stone.
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this book.Analogous to the way in which species evolve by reacting to the interplay of nature
and nurture,principles of nervous system function evolve from the interaction of science
and research. Thus the selection of these concepts is somewhat arbitrary; we could
have chosen more or different principles.
The reason for extracting guiding principles is just as important as their content
or wording. You reviewed the methods and treatments of neuropsychology in Chapter
15.We invite you now to revisit the functional principles that you first studied in Chapter
2, knowing what you know now about neuropsychology, brain and behavior, and
how they work together.
Your task is to synthesize the large body of information that you have learned into
an integrated theory of how the brain works. Perhaps the overriding message that
emerges from this effort is that mental activity results from brain activity. Through research,
we can eventually understand how this process takes place.
Principle 1: Information-Processing Sequence in
the Brain Is “In Integrate Out”
Most neurons have afferent (incoming) connections with tens or sometimes hundreds
or thousands of other neurons, as well as efferent (outgoing) connections to neurons
and many other cell types, such as muscle cells. The parts of the nervous system make
a great many connections with one another. Sensory and motor systems interact constantly
to control the organism’s interaction with its environment.
The entire brain receives inputs, creates information, and produces behavior, as
charted in Figure E-2. To the animal whose brain is engaged in this process, the creation
of information from inputs represents reality. The more complex the brain circuitry,
the more complex the reality created and, subsequently, the more complex the
thought. The emergence of thought that enables consciousness may be the brain’s ultimate
act of integration.
THE NEURON IS THE BASIC UNIT OF ANATOMY,
PHYSIOLOGY, AND COGNITION
Neurons are remarkably similar in all species, no matter where they are found in the
nervous system. The three basic parts of the neuron are the cell body, the dendrites,
and the axon, including the axon terminal, or end foot (Figure E-3). The neuron is the
basic unit of information processing, of brain plasticity, and even of cognition.
Drugs, for example, act at the level of individual neurons, and individual neurons
are what an animal’s experiences change. Individual neurons also communicate with
one another to generate sensation and perception and to create behavior. Differences
610 ! EPILOGUE
Eight Principles of Nervous System Function
Principle 1: Information-processing sequence in the brain is ”in ! integrate ! out.“
Principle 2: Sensory and motor functions throughout the nervous system are separated.
Principle 3: Inputs and outputs to the brain are crossed.
Principle 4: Brain anatomy and function display both symmetry and asymmetry.
Principle 5: The nervous system works through excitation and inhibition.
Principle 6: The nervous system functions on multiple levels.
Principle 7: Brain components operate both parallelly and hierarchically.
Principle 8: Functions in the brain are both localized in specific regions and distributed.
Table E-1
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Source Inputs Integration
Cellular
level
Outputs
N1 = neuron 1
N4
N5
N1
N2
N3 N6
N7
N8
Nuclei
level
Area
A
Area
B
Area
X
Area
Y
Area
Area Z
C
Brain
level World Brain Behaviors
Brains process
information on the
level of signaling
molecules from
cells (neurons)…
1
The same kind of
process takes place
between groups of
cells (nuclei) and
larger areas of
the brain.
These complex
cellular interactions
enable the brain to
translate
information from
the world into
behavior.
…and then sent
to neurons that
control an
action such
as movement.
3
…that are
integrated at
other neurons…
2
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among brains are due to differences in how individual neurons are distributed, organized,
and connected.
As brains have evolved to be larger and much harder to build to an exact blueprint,
nature’s solution has been to create extra neurons that duplicate the function of
other neurons. The strategy in developing a brain with many neurons is to shed unused
and unnecessary neurons, sculpting the brain to the organism’s current needs and
experiences.
Not only does this strategy prevent dependency
on the survival of each individual neuron,
it also allows great flexibility in adapting to specific
environmental conditions. An organism can
spend its energy in maintaining neurons required
in daily life. Allowing unneeded neurons
to die does not result in the loss of any essential
mental or behavioral function. Because the neuron
is the functional unit of the brain, investigating
what a neuron looks like, how it conducts
information, and how it works with other neurons
to produce behavior remains a focus for
studying the function of the brain and understanding
how the brain produces behavior.
THE SYNAPSE IS THE KEY SITE OF NEURAL
COMMUNICATION AND LEARNING
Dendrites, which are essentially extensions of the cell body’s surface, allow a neuron to
collect information from other cells, whereas the axon provides a pathway for passing
that information along. Although the dendrites and axon both handle messages, the
business site for communication is the synapse (Figure E-4).
WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 611
Figure E-2
Levels of Neural Processing The brain
integrates and makes decisions about
information at increasingly complex
levels of organization.
Collecting
information
Integrating
information
Flow of
information
Sending
information
Axons from
other neurons
Cell body Axon
End feet
Dendrites of
target neuron
Dendrites
Nerve cells collect
information,…
…and send it on to other
neurons or organs.
…process it,…
Figure E-3
Processing Unit A neuron is made up
of dendrites, which collect information
from other cells; an axon, which
communicates this information to other
neurons; and a cell body, which processes
the information and provides the energy
required to keep the operation going.
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612 ! EPILOGUE
Capillary
Muscle
Dendrites Cell body Axon
Synapses occur
between
dendrites,…
…between axons and various
other parts of the neuron,…
…and between axons and
blood vessels and muscles.
Figure E-4
Synaptic Connections
Drugs, hormones,
neurotrophic factors,
experiences
Synaptic change
Behavioral change
Synapses occur most often between an axon terminal of one neuron and a dendrite,
cell body, or axon of another neuron. The primary mode of communication
across most synapses is chemical. The chemical either alters channels on the receiving
(postsynaptic) neuron or initiates postsynaptic events through second messengers
(Chapter 5).
Synaptic activity can be influenced in several ways. The most direct route is either
to increase or decrease the amount of chemical transmitter released into the synaptic
cleft or to enhance or attenuate that chemical’s action on its postsynaptic receptor. This
route is the primary route of action of most drugs (Chapter 7).
There are less-direct routes, too. One effect of repeated exposure to drugs is either
to change characteristics of the postsynaptic membrane (such as the number of receptor
sites on it) or to alter the number of synapses. The number of synapses may be increased
by the addition of new synapses to the existing neurons; the synaptic space may
be increased by the addition of dendritic spines.
Changes in receptors or in the number of synapses are likely events in processes
such as learning and drug addiction. Indeed, synaptic change is required for virtually
any behavioral change, whether the change is related to learning, to development and
aging, or to recovery from brain injury. Because synaptic change is the key to behavioral
change, it follows that factors that enhance or diminish synaptic change (such as
neurotrophic factors, drugs, hormones, or experiences) will stimulate or retard behavioral
change.Many new treatments for behavioral disorders are designed to maximize
synaptic change.
CONSCIOUSNESS ORGANIZES BRAIN PROCESSING AND
THE BEHAVIOR PRODUCED BY THE BRAIN
We take for granted that we are conscious but debate whether other animals are. Consciousness
implies that we act not simply in relation to immediate circumstances but
also on the basis of memory and further implies the ability to communicate the reasons
for our actions to others. Simply stated, we think about our actions and articulate
our reasons. Clearly, other animals have memory and, clearly, they have communication
systems. But are they conscious in the way that humans are?
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Presumably, consciousness provides an adaptive advantage when a large
amount of information must be processed before we decide how to behave in a
particular situation. But behaviors that depend on conscious processing are
slower than automatic behaviors.As a result, conscious analysis is usually applied
to tasks where speed is not critical, such as discriminating between the various
colors of socks in a drawer.
In contrast, rapid automatic movements, such as swinging a baseball bat at a
ball, are usually performed without conscious control. As you learned in the discussion
of the ventral and dorsal streams of the visual system (Chapter 8), the distinction
between conscious and unconscious processing is fundamental to the
difference between thinking about objects and moving in relation to objects.Very
likely, the conscious processing of sensory information was enhanced by the emergence
of language,which,may have evolved in part to categorize information.
Many other animals have brains that are similar to ours, they have memory,
and they can communicate. These are reasons to believe that animals are in some
sense also conscious. But, because consciousness appears to be a specialized
function of only certain regions of the brain, many kinds of consciousness may
have evolved and we may be unique among animal species in having a self-aware
consciousness not common to other animals.
Principle 2: Sensory and Motor Functions
Throughout the Nervous System Are Separated
The segregation of sensory and motor functions exists throughout the nervous system
(review the law of Bell and Magendie in Chapter 2). Distinctions between motor and
sensory functions become subtler in the forebrain.
THE BRAIN CREATES A REPRESENTATION OF THE
EXTERNAL WORLD AND PRODUCES BEHAVIOR
IN RESPONSE TO THAT WORLD
Most animals with a multicellular brain have a common problem. They must move
from place to place to eat and to reproduce. These movements, which are controlled by
the nervous system, cannot be random. Rather, they must be made in response to the
external world where food and mates are found. This external world is created by the
nervous system through inputs from various sensory receptors.An animal’s perception
of what the external world is like therefore depends on the complexity and organization
of its nervous system.
Recall that different animals, such as dogs, bats, and chimpanzees, have developed
different “views” of the external world. For a dog, the world is dominated by odors; for
a bat, it is largely a world of sounds; and, for a
chimpanzee, colors are in the forefront of perception.
None of these representations of the external
world are more “correct” than the others.
They are simply different perspectives on what is
“out there” to be perceived.
Each representation creates a unique picture
that suits the behavioral repertoire of the animal
species. The behavior of dogs is driven by smells,
whether it is the smell of a strange dog, a potential
mate, or a possible prey. The flight of bats is
WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 613
Some neural processing happens so quickly
that we cannot be aware of it. The ball
coming out of the pitcher’s hand will travel
too fast for Hideki Matsui to consciously
see it, but he may still get a hit.
Even though bats create a world
largely through sound rather than
sight, they manage to move from
place to place without much trouble.
Employing echolocation, this bat ably
navigates through a mesh screen in
the dark.
Steven Dalton/NHPA
Investigate the sensory systems of the
brain in the modules on the Central
Nervous System and the Visual System on
the CD.
Ezra Shaw/Getty Images
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614 ! EPILOGUE
guided by auditory information, as when bats use sound to locate insects to eat. And
the behavior of chimpanzees is driven by color, the best example being to spot ripe fruit
in trees.
The brains of animals do something else as well: they create knowledge about the
world. They keep track of where objects are, where food may be found, where safe
sleeping places are located. As brains evolved into larger and larger organs, the amount
of knowledge processed and stored grew so big that some mechanism for organizing it
was needed.
One solution to the problem of categorizing information is to create some form of
coding system, of which human language is the ultimate example. In essence, the earliest
function of language may have been to organize the brain’s information. Language,
in other words, evolved for the brain to talk to itself. Later, language also provided a way
to share knowledge between brains.
Given the achievements of the human species in all these behavioral functions—
representing the world and moving about in it, acquiring and organizing knowledge—
our brain’s evolutionary development has clearly been very successful indeed. Still, the
human nervous system is not special: many kinds of coding and language likely allow
each animal species to succeed at its specialized mode of life.
BRAIN ORGANIZATION SEGREGATES SENSORY
INFORMATION USED FOR ACTION AND FOR KNOWLEDGE
In the ordinary course of our daily lives, we operate under the illusion that our behavior
is conscious.We believe that we give conscious commands to produce purposeful
movements. Usually, we are unaware that many of our actions, even very complex actions,
are performed without conscious control.We are unaware that we shape our fingers
to the objects that we are about to grasp (Chapter 10).We are surprised to learn
that, subsequent to temporal-lobe injury, we can reach for objects that we cannot consciously
see and that, subsequent to parietal-cortex damage, we can misreach for objects
that we can see.
This dichotomy between conscious action and unconscious action shows us that
the brain segregates actions that require conscious reflection from those that require
only action. Reaching for a handrail on a moving bus would not be an effective protective
action if we had to think about it for any length of time before doing it.
Much of our behavior can be divided into categories of knowledge and action. For
example, basketball is a complex sport, and knowledge of rules and strategies is required
to understand the game.But an experienced player probably gives little attention to rules
and strategies and catches, throws, and shoots the ball almost automatically.
Shooting a basketball can be learned in a single trial, but shooting it accurately
takes many thousands of trials. Many skills can similarly be divided into these action
and knowledge categories. Because the brain segregates action and knowledge, complex
behavior also can be segregated into categories of largely more conscious and
largely more automatic, as can brain regions.
ANIMALS ENGAGE IN BEHAVIORS FOR MULTIPLE REASONS
One of the most difficult questions to answer is why animals engage in behaviors, especially
why they perform particular behaviors at particular times. To address this
question, in Chapter 11 we considered the story of Roger, who seemed to have strange,
indiscriminate food preferences.We also considered the housefly and learned that what
appears to be purposeful behavior is really a response to stimuli coming from its feet
and esophagus (Figure E-5).
In addition, we examined why cats kill birds, factors that affect the annual cycle of
polar bears, and ideas about why we sleep and dream. We found it helpful to classify
Foregut stretch
receptors
Taste
receptors
Esophagus
Proboscis
Figure E-5
Prewired Behavior A housefly’s taste
receptors are on its feet. Stretch receptors
in its foregut tell it when it is full.
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WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 615
the many different kinds of animal behaviors as either regulatory or nonregulatory.
Regulatory behaviors maintain basic body functions, such as constant body temperature
or circadian patterns of sleeping and waking. Most regulatory behaviors require
little brainpower and are largely controlled by the hypothalamus and associated brainstem
structures.
It is more difficult to say why we engage in nonregulatory behaviors.We seek stimulation,
finding an absence of sensory input intolerable.We also seek mates, orienting
much of our lives around this behavior and activities associated with it. In addition, we
make plans and organize our behaviors temporally. Searching for the reasons behind
these nonregulatory behaviors led us to investigate the anatomical structures that control
each of them.
Although we still do not know much about the reasons for many of our nonregulatory
behaviors, we can draw several conclusions. Above all, behavior is controlled by
its consequences. These consequences may shape the behavior of a species or the behavior
of an individual organism. Behaviors that are adaptive and brains that are likely
to engage in adaptive behaviors are selected in the course of evolution.
We learned that cats kill birds because neural circuits in the brainstem control
these behaviors. Activation of these circuits is presumably rewarding, and so, in
a sense, animals engage in many behaviors because the behaviors feel good. We
learned, too, that animals do not need to actually engage in a rewarded behavior
to experience this positive feeling. Electrical stimulation of the attendant neural circuits
appears to be just as rewarding (perhaps even more so) than actually using the
circuits.
Because objects can take on different meanings, there are different reasons for our
actions. This difference is illustrated in Chapters 7 and 11, with the use of the terms
wanting and liking.Wanting is thought to be controlled by systems related to need, such
as primary hunger and primary thirst, whereas liking is thought to be controlled by
other neural structures that are sensitive to experience.
Principle 3: Inputs and Outputs to the Brain
Are Crossed
Most of the brain’s input and output pathways are crossed. Each hemisphere receives
sensory stimulation from the opposite (contralateral) side of the body and controls
muscles on the opposite side as well. Crossed organization explains why people who
experience strokes in the left cerebral hemisphere may have difficulty sensing stimulation
to the right side of the body or moving body parts on the right side. The opposite
is true of people with strokes in the right cerebral hemisphere.
The human visual system is crossed in a more complicated way than are sensory
and motor systems for other parts of the body or for animals with eyes on the sides of
their head, such as rats (Chapter 8). The human brain divides each eye’s visual field
into a left half and a right half. The information that either eye receives from the left
visual field is sent to the right side of the brain, and the information that either eye receives
from the right visual field is sent to the left side of the brain.
A crossed nervous system must join the two sides of the perceptual world together
somehow. To do so, innumerable neural connections link the left and right sides of the
brain. The most prominent connecting cable is the corpus callosum, which joins the
left and right cerebral hemispheres with about 200 million nerve fibers.
An important exception to the crossed-circuit principle is in the olfactory system.
Olfactory information does not cross but rather projects directly into the same (ipsilateral)
side of the brain.
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Principle 4: Brain Anatomy and Function Display
Both Symmetry and Asymmetry
Even though the left and right hemispheres appear anatomically similar and share
many functions, some, such as the articulation of speech, are lateralized to a single
hemisphere in most people. One reason that functions are lateralized may be the
greater efficiency of having a single neural network control a complex behavior that
depends on multiple sources of sensory input, knowledge, or both. For instance, language
or birdsong produced by a brain that has bilateral control of the sound-producing
apparatus is hard to imagine. After all, an organism cannot simultaneously make
two different sounds, one produced by each hemisphere.
A single control system therefore makes more sense. This concept can be easily applied
to other functions. For example, although we can move our limbs independently,
many of our movements, such as eating or dressing, require limb cooperation. Control
of such behaviors clearly necessitates the integration of multiple
sources of sensory input and multiple movements. The
nervous system has evolved lateralized networks to oversee
these functions.
It is tempting to overemphasize the asymmetrical organization
of the brain, especially the cerebral hemispheres. In
fact, however, both sides of the brain undertake most brain
functions. Both sides process sensory inputs from all the sensory
domains, and both sides produce movements of one
side of the body. The brain, in other words, has both symmetrical
and asymmetrical organization (Figure E-6).
Even a language function, which we think of as lateralized,
has both symmetrical and asymmetrical aspects (Chapter
9). It is the output apparatus for language that must be
controlled unilaterally. There is no obvious reason why the receptive aspects of language
must be unilaterally controlled, and, in fact, the right hemisphere does have receptive
functions, especially for nouns.
Because functions are both symmetrically and asymmetrically organized, our
brains can, in a sense, operate as two different brains. In fact, the hemispheres actually
do act separately if the corpus callosum is severed (Chapter 14).
Principle 5: The Nervous System Works Through
Excitation and Inhibition
The juxtaposition of excitation and inhibition is central to nervous system functioning.
The same principle that governs the production of behavior governs the activity
of individual neurons. The activity of neurons and neural systems is literally a balancing
act between the forces of inhibition and excitation.
The human nervous system is designed to balance excitation and inhibition. To
function, we maintain homeostatic balances of our regulatory systems (Chapters 7, 11,
and 12).We also maintain homeostasis with our external world, either by changing the
world or adapting to it (Chapters 13, 14, and 15).
As you have progressed through this book, you have seen that there is an interplay
of excitation and inhibition at many levels of nervous system function.At the level
of the cell and its components, single neurons can be either excited or inhibited, and,
through their neurotransmitters, cells act to stimulate or inhibit one another (Figure
E-7). An example in vision is how the activity of single retinal ganglion neuron can
616 ! EPILOGUE
Figure E-6
Superficial Differences Although at
first glance the brain’s hemispheres
appear identical on the right and the
left sides, closer inspection reveals that
they are asymmetrical. The brain’s
functions, however, are both
symmetrical and asymmetrical.
Parietal
lobe
Temporal
lobe
Left hemisphere Right hemisphere
Lateral
fissure
The left lateral fissure is
more horizontal,…
…and the right lateral fissure
bends upward more.
As a result, the parietal lobe is
larger on the left…
…and the temporal lobe is
larger on the right.
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Review the basics of excitation and
inhibition in the module on Neural
Communication on the CD.
be excited or inhibited by stimulation to its different parts, as shown
in Figure E-8.
Beyond the level of the cell, the dual processes of excitation and
inhibition continue to apply. For instance, systems in the reticular
formation controlling sleep–wake cycles essentially balance the inhibition
and activation of forebrain systems (Chapter 12). Similarly,
motor control includes the inhibition of some movements while
other movements are being activated (Chapter 10).
Many diseases can be thought of as disorders of excitatory and
inhibitory signals.Huntington’s chorea, for example, is the loss of the
ability to inhibit choreiform (convulsive) movements, whereas depression
is an inability to activate many kinds of behaviors (Chapter
15). Some diseases are characterized by changes in both inhibition
and excitation. Parkinson’s disease features both an uncontrollable
tremor and difficulty in initiating movement, and schizophrenia may
feature both flattened emotions and sensory hallucinations. The release
of behaviors such as tremor or hallucination represents a loss of
inhibition, whereas the absence of behaviors such as movement or facial
expression represents a loss of excitation.
Principle 6: The Nervous System Functions
on Multiple Levels
Similar sensory and motor functions are carried out in various parts of the central
nervous system: the spinal cord, brainstem, and forebrain. But why are multiple areas
with overlapping functions needed? Putting all the controls for a certain function in a
single place seems simpler.Why bother with duplication? It turns out that, as the brain
evolved, new areas were added, but old ones were retained. The simplest solution has
been to add new structures on top of existing ones.
Among the millions of animal species that inhabit our planet, very few have nervous
systems. Of those that do, still fewer have brains, and very few have large brains.
The nervous system and the brain likely began with a single cell that first became more
complex by incorporating new organelles and then, by dividing, organized into a primitive
nervous system and eventually into a brain.
Stimulate
Inhibitory
pathway
Excitatory
pathway
Stimulate
Oscilloscope
Motor neuron
S S
EPSP IPSP
Time (ms) Time (ms)
Excite Inhibit
Voltage (mV)
Figure E-7
Neural Integration Researcher John C. Eccles used the experimental
setup shown here to demonstrate information integration at the
neural level (Chapter 4). Stimulation of a neuron’s excitatory pathway
produces a membrane depolarization called an excitatory postsynaptic
potential (EPSP). Stimulation of the inhibitory pathway produces a
membrane hyperpolarization called an inhibitory postsynaptic potential
(IPSP).
ON
OFF
Light strikes
center
Excitation
Inhibition
Light strikes
surround
ON
OFF
Light stimulus
in a part of the
visual field
Receptive field
of a ganglion cell
Response of cell to stimulus at left
0 1 2 3
Time (s)
0 1 2 3
Time (s)
Figure E-8
Play of Light The receptive field of a
retinal ganglion cell with an on-center
and off-surround responds to the
presence or absence of light. A spot of
light in the center receptive field
excites the neuron but, when the light
shines on the surround, the cell is
inhibited (Chapter 8).
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In short, all brain cells descended from a first brain cell, all nervous systems
evolved from a first nervous system, and all brains evolved from a first brain. Brain
cells, nervous systems, and the brain did not evolve in isolation, however. Brain cells
and muscle cells evolved together to form more-complex networks, suggesting that
the primary evolutionary force sculpting these organs was and is the production of
movement.
We have seen that true cells, those with nuclei and other organelles, evolved from
simpler forms, and multicellular organisms evolved from single-celled organisms.We
have also seen that muscles and neurons are the distinguishing feature in
only one of the five kingdoms of living organisms, the animals.And we have
seen that, across the 15 phyla of animals, a nervous system first appears and
then becomes more complicated until, in only one of these phyla, the chordates,
the first brain makes its appearance (Chapter 1).
Among the seven classes of chordates, the brain becomes more complex;
but, in only two of these classes, birds and mammals, does the brain
become especially large and complex. Only in mammals has a true neocortex
evolved, and the neocortex becomes large in only a few orders, including
whales and primates. Among the primates, the cortex becomes
especially large in the apes and reaches its largest size in the human family.
In the only remaining member of the human family, we modern humans,
the cortex has evolved its largest and most complex form (Figure E-9).
Because brain cells, the nervous system, and the brain evolved gradually and because
representative animals having nervous systems of various complexities still exist,
neuroscientists are able to use a wide range of species of living organisms and animals
to study functions of the human brain. Because we have an evolutionary history in
common with other animals, we are not special, but we are specialized.
Principle 7: Brain Components Operate Both
Parallelly and Hierarchically
The brain and spinal cord are semiautonomous areas organized into functional levels.
Even within a single level, more than one area may take part in a given function.With
these different systems and levels, how do we eventually obtain a unified conscious
experience?
This question focuses on the binding problem: how the brain ties together its various
activities into a whole perception or behavior. The solution must somehow be related
to how the parts of the nervous system are connected. The two alternative
possibilities for “wiring” the nervous system are serial circuits and parallel circuits.
THE PRINCIPLE OF COMMON DESCENT RESULTS IN
A HIERARCHY OF COMPLEXITY IN THE EVOLUTION
OF THE BRAIN
In the evolution of complex nervous systems, simpler and evolutionarily more primitive
forms have not been discarded and replaced but rather have been added to. As a
result, all anatomical and functional features of simpler nervous systems are present in
the most complex nervous systems, including ours.
The bilaterally symmetrical nervous system of simple worms is common to complex
nervous systems. Indeed, the spinal cord that constitutes most of the nervous system of
the simplest fishes is recognizable in humans, as is the brainstem ofmore-complex fishes,
amphibians, and reptiles. The neocortex, although particularly complex in dolphins and
humans, is nevertheless clearly the same organ found in other mammals.
618 ! EPILOGUE
Figure E-9
Containing the Brain In the course of
human evolution, the relative size of the
brain has increased threefold, as
illustrated here by a comparison of the
skulls of Australopithecus afarensis (left),
Homo erectus (center), and Homo
sapiens (right).
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Hierarchy is manifest in the complex behavior of adult humans, in that it is a
mixture of many behaviors that are clearly recognizable in other animals, including
regulatory behaviors, emotional behavior, cognitive functions, and more specialized,
nonregulatory behaviors seen only prominently in humans. The addition and integration
of new levels of complexity in the hierarchical organization of the brain is seen
not only in adult behavior but also in the development of the human brain from infancy
into adulthood. Hierarchical organization accounts for the increasingly more
complex behavior that characterizes development as well.
The increasing complexity of movement and cognitive functions are manifestations
of the maturation of successive levels of a hierarchally organized brain (see Figure E-2).
In addition, the abnormalities associated with brain injury and brain disease that seem
bizarre when considered in isolation are only the normal manifestation of parts of a hierarchically
organized brain.Through the principle of hierarchy,we can see that our evolutionary
history, our developmental history, and our own personal history are
integrated at the various anatomical and functional “levels” of the nervous system.
PATTERNS OF NEURAL ORGANIZATION ARE PLASTIC
The brain is plastic in two fundamental ways:
1. Although we tend to think of regions of the brain as having fixed functions, the
brain has a capacity to adapt to different experiences by changing where specific
functions are represented. For example, a person with an amputated arm has an
increased representation of the face in the somatosensory cortex, as shown in Figure
E-10. In the absence of the limb, the face becomes more sensitive (Chapter 10).
2. The brain is also plastic in the sense that the connections among neurons in a given
functional system are constantly changing in response to experience. This type of
plasticity is manifested in our capacity for learning from experience and for subsequently
recalling learned material (Chapter 13).
One result of brain plasticity is that animals can acquire culture,
patterns of behavior that are not easy to predict simply by studying
brain anatomy and function. Many species of animals display behaviors
that differ, depending on a specific group of animals of that
species. Different pods of killer whales have different diets and different
groups of chimpanzees use different kinds of tools. Nevertheless,
we humans are specialized in the extent to which culture plays a role in
our lives.
We have learned to read, to calculate, to compose and play music,
and to develop the sciences.Clearly, the human nervous system evolved
long before we mastered these achievements. In turn, culture now plays
a dominant role in shaping our behavior. Because we drive cars, use computers, and
watch television, we and our nervous systems must be different from those of our ancestors
who did not engage in these activities.
Principle 8: Functions in the Brain Are Both
Localized in Specific Regions and Distributed
The parts of the brain make a great many connections with one another. This connectivity
is the key to its functioning. Sensory information, knowledge, and the control of
movement are all represented at multiple levels in the nervous system, beginning at the
spinal cord and ending in the association cortex (Figure E-11).
WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 619
Ball of
thumb
Thumb
Index
finger
Amputee
Cotton swab
Pinkie
finger
Figure E-10
Brain Plasticity When their faces are
lightly touched, amputees feel as if their
missing hands are being touched.
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These multiple levels of representation imply that functions
can be only partly localized to specific regions in the
brain. In fact, functions and controls are both localized and
distributed. You have seen such an example of localized and
distributed function in the organization of the sensory and
motor systems.
Clearly, there are sensory pathways into the brain and,
just as clearly, there are motor pathways out of the brain. Although
sensory impressions and motor actions can occur in
isolation one from the other, neither can ever be truly normal
without the other. For every function, there are parallel and
distributed systems of control.For the somatosensory system,
the different body senses have the same anatomical pathways
to some extent and can function in isolation, but their conjoint
operation provides us with our normal body image.
A key problem in studying the brain is the extent to
which functions can be thought to reside in specific locations.
A fundamental difficulty in localizing functions begins with the problem of defining
what a function is. Consider motivation. In Chapter 11, we used the psychological
construct of motivation as a shorthand way to describe the processes that initiate various
behaviors. But motivated behavior ranges from basic needs, such as maintaining a
constant body temperature, to lusting after an abstract concept, such as wealth.The neural
systems underlying such disparate behaviors are clearly going to be segregated.
Similarly, wanting sexual activity and engaging in it are two types of behavior organized
by different neural pathways. Apparently, the function that we call sexual behavior
has many aspects, and these aspects reside in widely separated areas of the brain.
A similar analysis may be applied to most other behaviors, a prime example being
memory. Memories are often extremely rich in detail and may include sensory detail,
emotions, words, and movement. As described in Chapter 13, there are many types of
memory processing, including the implicit–explicit distinction. As with sexual behavior,
one simple incident may be encoded in different places in the brain to form a
“memory” of the event.
An implication of the concept of localized and distributed functions is that damage
to a small area of the brain produces focal symptoms, but it takes massive brain
damage to destroy a function completely. A relatively small injury can destroy some
aspect of memory, but it takes a very widespread injury to destroy all memory capability.
Thus, a brain-injured person may be amnesic for the explicit recall of new information,
but he or she can still recall a lot of explicit information from the past and
may retain implicit recall of new information.
NEUROSCIENCE IN THE TWENTY-FIRST CENTURY
As you reflect on what you have learned in this book, you might wonder what we will
learn about the brain in the twenty-first century. It is often said that most of what we
now know about brain function was discovered in the 1990s, the so-called “decade of
the brain.” There is some truth in this statement. At the beginning of the 1860s, investigators
such as John Hughlings-Jackson were just starting to develop a vague idea of how
the brain is organized.And the brain’s chemical synapses were unknown until the 1950s.
With the research technology of recent years, however, many new insights have
come to light. Investigators have now begun to understand the important process of
how genes control neural activity. The development of new imaging techniques such
620 ! EPILOGUE
Basal ganglia
Cerebral
cortex
Frontal
lobe
Amygdala
Hippocampus
Specific areas of the cortex
are part of circuits for motor
activity, vision, memory,
and other functions.
The basal ganglia are part
of circuits for voluntary
movement, and movement
disorders such as Parkinson’s
disease result from neural
malfunction in that area.
Some memory and spatial
functions are partly
localized in the
hippocampus,…
…and other processes, such
as emotion, rely on circuits
that include the amygdala.
Figure E-11
Neural Connectivity Functions
are localized in specific parts of
the brain, but different aspects of
a function—types of memory, for
example—may be localized in more
than one area.
Rotate the brain and investigate brain
anatomy in the module on the Central
Nervous System on the CD
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as fMRI and ERP have opened up the normal brain to cognitive neuroscientists, allowing
them to investigate brain activity in laboratory subjects. As we reflect on the
study of brain and behavior in the past 150 years, we can only marvel at how far it has
advanced and how much potential for future discoveries lies just at our doorstep.
Studies of brain and behavior have also begun to capture the public imagination.
Whereas explanations of events in regard to brain function were unknown to the general
public 25 years ago, today, the media usually report new discoveries in neuroscience
and their possible applications weekly.
If we really understood the brain, we could build a robot behaviorally indistinguishable
from ourselves, but this possibility exists today only in the realm of science
fiction. As scientists have uncovered the complexities of emergent properties of genes,
proteins, and neurons, the possibility of building a “humanoid robot” appears to be receding
rather than growing closer. Most see the more short term goal of neuroscience
as restoring normal behavior by repairing a damaged nervous system.
One day we will likely be able to stimulate processes of repair not only in malfunctioning
brains but in injured spinal cords as well. These advances will come about
through the efforts of neuroscientists to understand how the brain produces and organizes
consciousness and, ultimately, overt behavior.
Along the way, we will learn how the brain stores and retrieves information, why
we engage in the behaviors that we do, and how we are able to read the lines on this
page and generate ideas and thoughts. The coming decades will be exciting times for
the study of brain and behavior. They offer an opportunity for us to broaden our understanding
of what makes us human.
WHAT HAVE WE LEARNED AND WHAT IS ITS VALUE? ! 621
EPILOGUE.qxd 2/8/05 3:13 PM Page 621

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