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LECTURE CONTENT:

✓ GENERAL ORGANIZATION OF NERVOUS SYSTEM

✓ PHYSIOLOGIC ANATOMY OF THE CEREBRAL CORTEX

✓ FUNCTIONS OF SPECIFIC CORTICAL AREAS

✓ MEMORY: TYPES, MECHANISMS

✓ LIMBIC SYSTEM

✓ HYPOTHALAMUS

✓ STATES OF BRAIN ACTIVITY

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The Nervous System

The Central Nervous System

The Brain

The Spinal Cord

The peripheral Nervous System

The Somatic Nervous System

The Autonomic Nervous System

The parasympatheti

c Nervous System

The Sympathetic

Nervous System

Structures of the

Cerebrum

Gyri of neural cortex: increase surface area (number of cortical

neurons)

Longitudinal fissure: separates cerebral hemispheres

Lobes: divisions of hemispheres

Central sulcus divides: anterior frontal lobe from posterior parietal

lobe

Lateral sulcus divides: frontal lobe from temporal lobe

Parieto-occipital sulcus divides: parietal lobe from occipital lobe

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Functional Principles of the

Cerebrum

➢ Each cerebral hemisphere receives sensory information

from, and sends motor commands to, the opposite side of

body

➢ The 2 hemispheres have different functions although their

structures are alike

➢ Correspondence between a specific function and a specific

region of cerebral cortex is not precise5

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Cerebral Cortex - main features:

• The cerebral cortex is a sheet of neural tissue that is

outermost to the cerebrum of the mammalian brain.

• It plays a key role in memory, attention, perceptual

awareness, thought, language, and consciousness.

• It is constituted of up to six horizontal layers, each of

which has a different composition in terms of neurons

and connectivity.

• The human cerebral cortex is 2–4 mm (0.08–

0.16 inches) thick.

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Most of the neurons are of three types:

◦ (1) granular (also called stellate),

generally have short axons and, therefore, function

mainly as interneurons that transmit neural signals only

short distances within the cortex itself

◦ (2) fusiform,

give rise to almost all the output fibers from the cortex

◦ (3) pyramidal

they are the source of the long, large nerve fibers that go

all the way to the spinal cord.8

I. Molecular Layer

II. External Granular Layer

III. External Pyramidal Layer

IV. Internal Granular Layer

V. Internal Pyramidal Layer

VI. Polymorphic Layer

Structure of cerebral cortex

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Six horizontal layers

most incoming specific sensory signals from the

body terminate in cortical layer IV

most of the output signals leave the cortex

through neurons located in layers V and VI

layers I, II, and III perform most of the

intracortical association functions

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Anatomical and Functional

Relations of the Cerebral Cortex to

the Thalamus and

Other Lower Centers

All areas of the cerebral cortex have

extensive to-and-from efferent and afferent

connections with deeper structures of the brain.

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The thalamus and the cortex together

are sometimes called the

thalamocortical system.

two directions:

1. from the thalamus to the cortex

2. then from the cortex back to essentially the same area of the thalamus.

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Association areas receive and analyze signals

simultaneously from multiple regions of both the motor

and sensory cortices as well as from subcortical structures.

The most important association areas are:

(1) the parieto-occipitotemporal association area,

(2) the prefrontal association area,

(3) the limbic association area.

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This association area lies in the large parietal and

occipital cortical space bounded by the somatosensory

cortex anteriorly, the visual cortex posteriorly, and the

auditory cortex laterally.

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Functions of specyfic

regions of

Parieto-occipitotemporal

Association Area

• provides continuous analysis of

the spatial coordinates of all parts

of the body as well as of the

surroundings of the body.

• receives visual sensory

information from the posterior

occipital cortex and simultaneous

somatosensory information from

the anterior parietal cortex.

An area begines in the posterior parietal cortex

and extending into the superior occipital cortex

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This is the major area for language

comprehension, called Wernicke's area.

It lies behind the primary auditory cortex in the

posterior part of the superior gyrus of the temporal

lobe.

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• Posterior to the language comprehension area, lying mainly

in the anterolateral region of the occipital lobe, is a visual

association area.

• This so-called angular gyrus area is needed to make

meaning out of the visually perceived words.

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The names are learned mainly through auditory input,

whereas the physical natures of the objects are learned mainly

through visual input. In turn, the names are essential for both

auditory and visual language comprehension.

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2. The Prefrontal

Association Area

This brain region has been implicated

in planning complex cognitive

behavior, personality expression,

decision making, and moderating

social behavior.

In 1861, the French surgeon, Pierre Paul Broca, described two patients who

had lost the ability to speak after injury to the posterior inferior frontal gyrus of

the brain.

Clinical studies of Broca's aphasia often assume that the deficits in these

patients are due entirely to dysfunction in Broca's area, thereby attributing all

aspects of the disorder to this one brain region.

N. F. Dronkers, O. Plaisant, M. T. Iba-Zizen and E. A. Cabanis Oxford Journals Medicine Brain

Volume130, Issue5 Pp. 1432-1441. 2007 22

Broca's Area

This area, is located partly in the posterior lateral prefrontal cortex

and partly in the premotor area. It is here that plans and motor

patterns for expressing individual words or even short phrases are

initiated and executed.

This area also works in close association with Wernicke's

language comprehension center in the temporal association cortex

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This area is found in the anterior pole of the temporal lobe, in the

ventral portion of the frontal lobe, and in the cingulate gyrus lying

deep in the longitudinal fissure on the midsurface of each cerebral

hemisphere.

It is concerned primarily with behavior, emotions, and

motivation.

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Facial recognition areas located

on the underside of the brain in

the medial occipital and temporal

lobes.

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The occipital portion of this facial recognition area is contiguous

with the visual cortex, and the temporal portion is closely

associated with the limbic system that has to do with emotions,

brain activation, and control of one's behavioral response to the

environment

Carl Wernicke, a German neurologist, discovered

another part of the brain, this one involved in

understanding language, in the posterior portion of the

left temporal lobe. People who had a lesion at this

location could speak, but their speech was often

incoherent and made no sense.26

Angular Gyrus (area 39)

If this region is destroyed while Wernicke's area in the temporal

lobe is still intact, the person can still interpret auditory

experiences as usual, but the stream of visual experiences

passing into Wernicke's area from the visual cortex (by the visual

occipital areas (areas 17, 18, and 19) is mainly blocked.

Therefore, the person may be able to see words and even know

that they are words but not be able to interpret their meanings.

This is the condition called word blindness.

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A first model of the general organization of language

functions in the brain was proposed by American

neurologist Norman Geschwind in the 1960s and

1970s.

This “connectionist” model drew on the lesion studies

done by Wernicke and his successors and is now

known as the Geschwind-Wernicke model.28

According to this model, each of the various characteristics of

language (perception, comprehension, production, etc.) is

managed by a distinct functional module in the brain, and each of

these modules is linked to the others by a very specific set of

serial connections.

The central hypothesis of this model is that

language disorders arise from breakdowns in

this network of connections between these

modules. 29

According to this model, when you hear a word spoken, this

auditory signal is processed first in your brain’s primary auditory

cortex, which then sends it on to the neighbouring Wernicke’s

area.

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Wernicke’s area associates the structure of this

signal with the representation of a word stored in your

memory, thus enabling you to retrieve the meaning of

the particular word.

In contrast, when you , the information is

perceived first by your visual cortex, which then transfers it to the

, from which it is sent on to Wernicke’s area.

Whether you hear someone else speak a word or you read the word

yourself, it is the mental lexicon in Wernicke’s area that recognizes

this word and correctly interprets it according to the context. For you

then to pronounce this word yourself, this information must be

transmitted via the arcuate fasciculus to a destination in Broca’s area,

which plans the pronunciation process.

Lastly, this information is routed to the motor cortex, which controls

the muscles that you use to pronounce the word. 32

Several decades ago, it was found that some patients

could receive significant relief from severe psychotic

depression by severing the neuronal connections

between the prefrontal areas of the brain and the

remainder of the brain, that is, by a procedure called

prefrontal lobotomy. 33

Subsequent studies in these patients showed

the following mental changes:

1. The patients lost their ability to solve complex problems.

2. They became unable to string together sequential tasks to

reach complex goals.

3. They became unable to learn to do several parallel tasks at the

same time.

4. Their level of aggressiveness was decreased, sometimes

markedly, and, in general, they lost ambition.

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Subsequent studies in these patients showed

the following mental changes:

5. Their social responses were often inappropriate for the occasion,

often including loss of morals and little reticence in relation to sex

and excretion.

6. The patients could still talk and comprehend language, but they

were unable to carry through any long trains of thought, and their

moods changed rapidly from sweetness to rage to exhilaration to

madness.

7. The patients could also still perform most of the usual patterns of

motor function that they had performed throughout life, but often

without purpose. 35

Deficits in the Prefrontal

Association Areas

Decreased aggressiveness and inappropriate social

responses

Inability to progress toward goals or to carry through

sequential thoughts

Deficits in the elaboration of thought, prognostication,

and performance of higher intellectual functions

("Working Memory") 36

Patients with prefrontal cortical lesions are

easily distracted, have poor concentration and

organization, have difficulty dividing or

focusing attention, and are more vulnerable to

disruption from interference, resembling

many facets of the behavioral features of

ADHD.

Deficits in the Prefrontal Association

Areas

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BRAIN LATERALIZATION

Brain lateralization

The human brain is divided into two

hemispheres but these paired structures are not

exactly symmetrical and often differ in their

size, form, and function.

This phenomenon is called brain

lateralization.

The two most lateralized functions in the

human brain are motor control and language. 39

Lateralization of motor

control

Lateralization of motor control is what determines

whether someone is right-handed or left-handed.

◦ When someone is ambidextrous-when they can use either hand as

easily as the other-it means that their brain is only partly

lateralized or not at all lateralized for motor control.

In right-handed people, the “dominant” hemisphere

for motor control is the left, while in left-handed

people, it is the right. 40

Lateralization of language

In the vast majority of right-handed people, language

abilities are localized in the left hemisphere.

But the opposite is not true among left-handed people,

for whom the picture is less clear. Many “lefties” show

a specialization for language in the left hemisphere,

but some show one in the right, while for still others,

both hemispheres contribute just about equally to

language. 41

Functional differences between left and right hemispheres:

In most people (90%), left brain (dominant hemisphere)

controls:

◦ reading, writing, and math

◦ decision-making

◦ speech and language

Right cerebral hemisphere relates to:

◦ senses (touch, smell, sight, taste, feel)

◦ recognition (faces, voice inflections)

Unclear dominance may lead to dyslexia 42

Left Hemisphere

Important for the

expression of positive

emotion

Damage to the L.H. leads

to loss of the capacity of

joy.

Activation in the L.H.

leads to tendencies to

approach other people.

Right Hemisphere

Important for the

expression of negative

emotion

Damage to the R.H. may

make people euphoric.

Activation in the R.H. leads

to tendencies to withdraw

from people. 43

Function of the Corpus Callosum and

Anterior Commissure

Fibers in the corpus callosum provide abundant bidirectional

neural connections between most of the respective cortical areas

of the two cerebral hemispheres except for the anterior portions

of the temporal lobes; these temporal areas, including especially

the amygdala, are interconnected by fibers that pass through

the anterior commissure.

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The functions of the corpus callosum and the

anterior commissure is to make information stored

in the cortex of one hemisphere available to

corresponding cortical areas of the opposite

hemisphere.

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1. Cutting the corpus callosum blocks transfer of

information from Wernicke's area of the dominant

hemisphere to the motor cortex on the opposite side of the

brain.

2. Cutting the corpus callosum prevents transfer of

somatic and visual information from the right

hemisphere into Wernicke's area in the left dominant

hemisphere.

3. Finally, people whose corpus callosum is completely

sectioned have two entirely separate conscious portions of

the brain.

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BEHAVIORAL AND MOTIVATIONAL

MECHANISMS OF THE BRAIN-THE

LIMBIC SYSTEM AND THE

HYPOTHALAMUS47

Reticular Excitatory Area of the

Brain Stem

The signals passing through the thalamus are

of two types:

1. Rapidly transmitted action potentials that excite the cerebrum

for only a few milliseconds. These originate from large neuronal

cell bodies that lie throughout the brain stem reticular area.

Their nerve endings release acetylcholine, which serves as an

excitatory agent, lasting for only a few milliseconds before it is

destroyed. 48

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Reticular Excitatory Area of the

Brain Stem

2. The second type of excitatory signal originates from large numbers

of small neurons spread throughout the brain stem reticular

excitatory area.

Most of these pass to the thalamus, but this time through small,

slowly conducting fibers that synapse mainly in the intralaminar

nuclei of the thalamus and in the reticular nuclei over the surface of

the thalamus. From here, additional small fibers are distributed

everywhere in the cerebral cortex.

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NEUROHORMONAL CONTROL

OF BRAIN ACTIVITY

Norepinephrine (NE) is a neurotransmitter, involved

in behaviours including alertness, anxiety, and

attention. Most norepinephrine cells cluster in a pair of

nuclei called the locus coeruleus, Latin for a “blue spot”

in the brain stem.

A second group of nerve cells arises deeper down in the

medulla, and delivers norepinephrine mostly to the

hypothalamus

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Dopamine is a neurotransmitter, a chemical used to carry messages

between neurons. Dopamine is produced in several areas of the brain,

including the substantia nigra.

Dopamine

Dopamine's effects are complex and poorly understood, but dopamine

appears to play a role in signaling reward in the brain. Many drugs of

abuse which give "pleasurable" or "calming" highs, such as cocaine and

nicotine, appear to work by mimicking dopamine in the brain

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When a signal comes down the axon, dopamine is released

into the synapse. It then crosses the synaptic cleft to the second

neuron, where it binds to and stimulates dopamine receptors,

generating a signal in the second neuron.

The dopamine is then released from the receptor and crosses

back to the first neuron where it is picked up by dopamine

transporters for re-use.

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But what happens when a

person takes a drug?

Cocaine (green), attaches to dopamine transporters (purple), thereby

blocking dopamine from being taken back up by the first neuron.

Thus dopamine can continue to stimulate (maybe over-stimulate) the

receptors of the second neuron because it remains in the synapse for a

longer period of time.

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Concept of Limbic System

Broca (1877) - ‘La Grand Lobe Limbique’

Papez (1937) - ‘Limbic Circuit’ - emotion

MacLean (1952) - ‘Limbic System’ - visceral brain

Nauta (1972) - ‘Septo-hypothalamo-mesencephalic continuum’

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In the early part of the twentieth century, researchers identified the

hypothalamus

as a key structure in the control of the autonomic nervous system (Karplus and

Kreidl, 1927). On the basis of these early observations, and their own work

(Cannon and Britton, 1925), Cannon and Bard proposed a hypothalamic theory

of emotion that consisted of three major points:

(1) the hypothalamus evaluates the emotional relevance of

environmental events;

(2) the expression of emotional responses is mediated by the

discharge of impulses from the hypothalamus to the

brainstem;

(3) projections from the hypothalamus to the cortex

mediate the conscious experience of emotion (Bard, 1928;

Cannon, 1929).

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In 1937 Papez added anatomical circuits in the

forebrain to the theory, but retained the central role of

ascending and descending connections of the

hypothalamus.

The Papez theory, in turn, was extended by MacLean

(1949, 1952), who called the forebrain emotional

circuits the visceral brain, and later, the limbic system.

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COMPONENTS:

Amygdaloid body

Hippocampus (“seahorse”)

Cingulate gyus

Parahippocampal gyrus

Hypothalamus

Mamillary bodies

Anterior nucleus of thalamus59

FUNCTIONS

“Emotional brain”

Emotional and motivational aspects of

behavior.

Provides emotional component to

learning process:

Especially the amygdala.

Associated with memory

Especially the hippocampus.

Associated with pain/pleasure, rage60

AMYGDALA

Large nuclear group in temporal lobe.

Afferents:

Olfactory tract

Solitary nucleus

Parabrachial nucleus

Limbic neocortex:

Cingulate gyrus

Parahippocampal gyrus

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FUNCTIONS OF THE AMYGDALA

Relate environmental stimuli to coordinated

behavioral autonomic and endocrine responses

seen in species-preservation.

Responses include:

Feeding and drinking

Agnostic (fighting) behavior

Mating and maternal care

Responses to physical or emotional stresses.

KLUVER-BUCY SYNDROME:

Results from bilateral destruction of

amygdala.

Characteristics:

Increase in sexual activity.

Compulsive tendency to place objects in mouth.

Decreased emotionality.

Changes in eating behavior.

Visual agnosia.63

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HYPOTHALAMUS

Hypothalamus and Limbic

System: Homeostasis

A major function of the nervous system is to maintain

homeostasis, or the stability of the internal environment.

The hypothalamus, which comprises less than 1% of the total

volume of the brain, is intimately connected to a number of

structures within the limbic system and brainstem.

Together the hypothalamus and the limbic system exert control

on the endocrine system the autonomic nervous system to

maintain homeostasis.65

Hypothalamus and Limbic

System: Emotion and Motivated

Behavior

Emotions and motivated behavior are crucial for survival:

◦ Emotional responses modulate the autonomic nervous system

to respond to threatening stimuli or situations.

◦ Emotional responses are adaptive. If you are prepared to deal

with threatening stimuli, you are more likely to survive and

reproduce.

◦ Motivated behavior underlies feeding, sexual and other

behaviors integral to promoting survival and reproduction.

◦ The hypothalamus and limbic system mediate these behaviors.

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Hypothalamus: Integrative

Functions

The hypothalamus helps regulate five basic physiological needs:

1) Controls blood pressure and electrolyte (drinking and salt appetite).

2) Regulates body temperature through influence both of the autonomic

nervous system and of brain circuits directing motivated behavior

(e.g. behavior that seeks a warmer or cooler environment).

3) Regulates energy metabolism through influence on feeding, digestion,

and metabolic rate.

4) Regulates reproduction through hormonal control of mating,

pregnancy and lactation.

5) Directs responses to stress by influencing blood flow to specific

tissues, and by stimulating the secretion of adrenal stress

hormones.

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How hypothalamic pathways

influence endocrine function?

The hypothalamus controls the endocrine system by

secreting oxytocin and vasopressin into the general

circulation from nerve terminals ending in the posterior

pituitary.

The hypothalamus also secretes regulatory hormones into

local portal circulation that drains into the anterior

pituitary.

Finally, some hypothalamic neurons influence peptidergic

neurons, synapsing at those neurons cell bodies or axon

terminals.

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Temperature regulation is a good

example of a hypothalamic servo-

control system To regulate temperature, integration of autonomic, endocrine, and

skelatomotor systems must occur. The hypothalamus is positioned

anatomically to accomplish this control and integration.

The set point for the system is normal body temperature.

The hypothalamus contains “feedback detectors” that collect

information about body temperature. These come from two sources:

◦ Peripheral receptors transmit information through temperature pathways

to the CNS.

◦ Central receptors are located mainly in the anterior hypothalamus.

Temperature-sensitive neurons in the hypothalamus modulate their

activity in relation to local temperature (blood temperature).

Distinct regions of the hypothalamus

mediate heat dissipation and heat

conservation

The anterior hypothalamus (preoptic area)

mediates decreases in heat.

Lesions cause:

◦ Chronic hyperthermia

Electrical stimulation causes:

◦ Dilation of blood vessels in the skin

◦ Panting

◦ Suppression of shivering

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Distinct regions of the hypothalamus

mediate heat dissipation and heat

conservation (2)

The posterior hypothalamus mediates

heat conservation.

Lesions cause:

◦ Hypothermia if an animal is placed in a cold

environment.

Microstimulation causes:

◦ Shivering

◦ Constriction of blood vessels in the skin71