6.1 Definition and Localization of Integrative Functions

integrative functions: sleeping/waking cycle
consciousness, language, thinking
memory, learning, motivation, emotion
brain area for integrative funtions: neocortex and limbic system

Functional Topography of the Neocortex

Cerebral localization versus hollistic views

Gall, early 1800's: Prenology,
skull 모양---> personality, mentality, moral characteristics
no adequate scientific foundation

specific function of particular cortical areas:
1) Broca: motor speech center, 1865
2) primary motor cortex: Fritsch & Hitzig, 1870
3) sensory speech center: Wernicke, 1874

Fig. 6.1
Kleist: highly discrete localization of individual mental functions
Lashley: size of the lesion, rather than site: equipotentiality (hollistic)

Boundaries of the association cortex

Fig. 6.2
association cortex: the regions to which no predominant sensory or motor fx
can be assigned.
large part of the cerebral cortex
1) parietal-temporal-occipital association cortex
: higher sensory functions and language
2) prefrontal association cortex
: higher motor functions
3) limbic association cortex
: memory and emotional aspects of behavior
Limits of cerebral localization, definiton of centers

predominantly concerned with the specific function

Role of Encephalization in Higher Brain Functions

brain weight (E) = K X body weight (P)2/3; K: encephalization factor
K: mouse: 0.06
chimpanziees: 0.3
human: 1.00
evolutionaly development:
relative increase in the neocortex
--- reduction elsewhere in the brain
due to decreasing sensory specialization
& a need for fewer motor response patterns
hunter and prey: progressive encephalization in vertebrates, carnivores
present brain wt: 200,000 years ago, 1,400 g
language about 40,000 years ago
Superior thinking and learning abilities
<---- quantitative change, increase in the number of neuronal
aggregates available for information processing


6.2 General Physiology of the Cerebral Cortex

Functional Histology of the Cerebral Cortex



General arrangement of the cortex, cortical layers

multilayered, folded
total surface area: 2,200 cm2 (47 cm X 47 cm)
thickness: 1.3-4.5 mm
volume: 600 cm3
109 to 1011 neurons+ glial cells
striate appearance, 6 layers Fig. 6-3, 6-5
neocortex (isocortex)
allocortex: 3-layered (archipallium, paleopallium)

Fig. 6-3
I. Molecular layer (plexifrom layer)
numerous fibers (tangential), few cells
II. External granular layer
III. External pyramidal layer
IV: Internal granular layer
V. Interanl pyramidal layer
VI. Fusiform-cell layer


Cortical maps

structural pattern of the isocortex is uniform
variation: cortical cytoarchitectonics
Brodmann's 50 area Fig. 6-4


Homotypical and heterotypical isocortex

histological area = particular function
Von Economo: five basic types: 1,2,3,4,5, gradual transition
Fig. 6-5
homotypical cortex: 2,3,4; contain all 6 layers
heterotypical cortex: 1,5; fewer than 6 layers
1: agranular cortex; prototype of the motor cortex, efferent
5: granular cortex (koniocortex); prototype of the sensory ctx, affer
2: dysgranular cortex

Fiber connections in the neocortex
cortical efferents (corticofugal fibers)
1) projection fibers
2) association fibers
3) commissural fibers
cortical afferents (corticopetal fibers)
1) thalamocotical
2) association 3) commissural fibers




Cortical neurons and the circuits they form

2 main types: Fig. 6.6
pyramidal cells: pyramidal shape, axon leaves the ctx
stellate cells: stellate shape, cortical interneurons

Layer I: apical dendrites of the pyramidal cells
axons of the stellate cells
tangential to the surface
local intracortical communication
afferent from nonspecific thalamus
Layers II & III:
small pyramidal cells
intercortical information transfer
afferents from nonspecific thalamus
Layer IV:
specific thalamic afferents (terminating on stellate, pyramidal cells
distribution to other layers
Layer V:
large pyramidal cell (giant cells of Betz in the motor ctx)
transfer of information to the subthalamic parts of the brain
Layer VI:
back to the thalamus, corticothalamic projection

perpendicular to the cortical surface:
processing particular kinds of information

concepts of histological and functional cortical columnar modules

Pyramidal cells:
apical dendrites: axodendritic synapses; excitatory
basal dendrites; inhibitory synapses

Stellate cells:
excitatory stellate cells: run perpendicular to the cortical surface
inhibitory stellate cells: parallel to the surface, basketlike
pericolumnar inhibition (basket cell)

various kinds of neurotransmitters


Electrophysiological Correlates of Cortical Activity


Biophysical properties of cortical neurons

Pyramidal cell: resting membrane potential: -50 to -80 mV
action potentials: 60-100 mV in amplitude, 0.5-2 ms dura.
originate at the axon hillock
axon을 따라, proximal dendrites, soma
up to 100 Hz
dendritic tree에서; dendritic generatting sites
fast prepotentials
(blocked by TTX, Na 채널)
slow dendritic action potentials
(blocked by Mg, Ca 채널)

Synaptic activity of cortical neurons

Excitatory postsynaptic potential (EPSP)
rise time: several ms
decay time: 10-30 ms

IPSP: 70-150 ms
less common than EPSP in the spontaneously active ctx
smaller amplitude
frequent long-lasting IPSP after activation of
the corticopetal sensory pathways.

frequency of cortical impulse activity elicited by PSP: low
usually below 10 Hz, not uncommonly below 1 Hz
resting potential: usually fluctuate in the range 3-10 mV
below threshold


Electrocorticograms (ECoG)

2 electrodes laid on the surface of the cerebral ctx
Fig. 6-7
continuous potential fluctuations, 1 - 50 Hz, 100 uV or more
normal conditions: frequency & amplitude
: species of animal, recording site, degree of wakefulness
in humans: awake but relaxed state, 8-13 Hz, occipital ctx, alpha waves
eyes open: alpha blockade, replaced by beta waves; 14-30 Hz
lower amplitude
Origin of the ECoG
reflects the postsynaptic activity of the cortical neurons
positive potential fluctuation: EPSPs in the deeper layers of the ctx
IPSPs in the superficial layers
negative potential fluctuation: 반대로

rhythmic activity of the ctx (alpha rhythm)
: induced largely by the activity of the deeper structures (thalamus)
Fig. 6-8
ablation of thalmus, deafferentation---> alpha 리듬 사라짐
decortication: no change in alpha rhythm
multiple thalamic pacemakers
reticular structures: synchronizing & desynchronizing action

Event-related potentials, ERPs

characteristic potential fluctuations that tend to appear after
psychological, motor and sensory events.
e.g.: rediness potential, expectancy potential, premotor positivity
Evoked potentials (EPs):
receptors (sensors), peripheral nerves,
sensory tracts, nuclei, other sensory structures를 자극시 출
Fig. 6-9:
somatic evoked potentials (SEPs)
: peripheral somatic nerve를 자극, recording from SI,SII
Primary evoked potential: from postcentral gyrus의 작은 지역
Secondary evoked potential: from extensive cortical region

origin of EP: reflection of the synaptic activity


The main value of EP measurement for clinical diagnosis

to test the intactness of peripheral sensory and subcortical pathways
Fig. 6.10: Auditory evoked potential (AEP)
6 distinct positive peaks
I: auditory nerve
II: cochlear nucleus
III: superior olive
IV & V: lateral lentiform nuclei, & inferior colliculi
VI: thalamic level
Visual EP (VEP)


Electroencephalogram (EEG)


Definition, mechanism of origin

1929-1938: Hans Berger
scalp에서, smaller amplitude & lower frequency
mechanism: same as ECoG

Recording and interpreting the EEG

standardized, recording site, recording conditions: Fig. 6.11
interpretation based on: Fig. 6.12
frequency, amplitude, shape and distribution of the waves in the EEG
proportions of the different kinds of waves

Forms of the EEG; diagnostic significance

Fig. 6.11
alpha waves: alpha rhythm: 8-13 Hz (10 Hz), eyes closed, occipital area
synchonized EEG
alpha blockade, eyes open
beta waves: 14-30 Hz (20 Hz), smaller amplitude, desynchronized EEG
theta waves: 4-7 Hz (6 Hz)
delta waves: 0.3-3.5 Hz (3 Hz)
slow waves during sleeping
EEG of children and adolescent: slower, more irregular,
exhibiting delta waves even in waking state

EEG: the only available method for the continuous quantification of
neuronal processes in the intact human brain
: the most important means of access to human information processing
and behavior-controlling mechanisms for both psychological and
clinical practice

Fig. 6.12
seizure potentials, cerebral trauma, metabolic intoxication
tumors, diffuse organic brain disease, psychoactive drug

isoelectric or flat EEG: a criterion for death
cortex (3-8 min) and brainstem (7-10 min): low ischimia tolerance
resuscitation limit
myocardium: 20 min, kidney: 150 min
organ transplants


Magnetencephalography, MEG

brain generates weak magnetic field
better spatial resolution of the site of origin of cortical activity
at present for research use

Cerebral Activity, Metaboilism and Blood Flow

brain consumes about 50 ml oxygen/min:
resting person에서, 대개 20% of the total oxygen requirement
15% of the cardiac output at rest
rate of perfusion is not uniform in all parts of the brain
cerebral cortex >>> white matter
Fig. 6.14
alpha wave EEG시: blood flows: frontal regions >> other areas
slight pain ---> primary sensory area
hand movment---> "
metabolic maps: monitoring the uptake of radioactive glucose
parallel with the changes of the regional blood-flow maps
regionally elevated neuronal activity---> local vasodilation


Imaging Procedures for the Representation of Brain Structures and Activities


X-ray computed tomography (CT)
0.5-1 mm resolution for a layer 2-13 mm thick
positron-emission tomography (PET)
4-8 mm spacial resolution, temporal resolution of 1 s
tomography by nuclear magnetic resonance (NMR)
1 mm resolution, thickness: 5-10 mm, temporal resolution: 10-20s










BRAIN FACTS

6.3 Waking and Sleeping (각성과 수면)
Circadian Periodicity as the Basis of the Waking/Sleeping Rhythm
The circadian oscillator
Protozoans---> Humans: rhythmical changes
rhythm coupled with 24 hour periodicity
earth rotation, tides, phases of the moon
annual cycle

passive vs active rhythmicity
---> free-running rhythm (shorter or longer than 24 hr)
---> biological clock (endogenous processes)
---> circadian rhythm (self-excited oscillator)
---> synchronized with 24-h cycle by external entraining signals
Circadian periodicity in humans
more than 100 parameters: changes cyclically with a 24 h period
body temperature: early morning <1-1.5 OC evening
waking/sleeping cycle
considerable number of circadian oscillators of somewhat diff. periods

free-running rhythm (bunkers or caves): Fig. 6-15
A: 24.0+-0.7 h ---> 26.1+-0.5 h somewhat longer
body temp. maxim: just before the onset of sleep
2 day after: phase shift: couple and decouple
B: extreme case: 48 h, bicardian rhythms
complete uncouple: autonomic body temp> 25.1 hr vs. 33.4 s/w
temperature clock is less flexible

flight (jet lag): to east---> shorthen
to west---> lengthened(phase delay), easier reentrainment
1 day/time zone: 1 h shift
body temperature: slowly reentrained

ratio of the duration of activity and rest times
within a circadian cycle is not kept constant
---> average circadian period is kept as constant as possible
---> circadian periodicity is the primary process
---> sleeping and waking are subordinate
side effects of endogenous circadian periodicity

significance of the circadian rhythms:
inherited
phylogenetic adaptation to the temporal structure of
our environmental events
internal copy of the schedule of environmental events
---> organism can adjust itself in advance to the changes
in environmental conditions to be expected at any time
---> performing certain actions at suitable times of the day
---> measuring time by means of the internal clock

pacemakers for the circadian rhythm:
in CNS
1. suprachiasmatic nucleus (SCN) in the ventral hypothalamus
---> regulating the activity cycle (S/W rhythm)
: input from the visual system
: synchronized with the VMH by close reciprocal connections
2. ventromedial nucleus of the hypothalamus (VMH)
---> temperature & feeding rhythm (glucose, corticoid level)

Phenomenology of Waking and Sleeping

Human waking/sleeping behavior
Neither waking nor sleeping is a homogeneous state of consciousness
수면은 단순한 무활동의 시기라기 보다는 일련의 연속적 상태
Stages of sleep: depth of sleep <--- intensity of a stimulus sufficient for
awakening
EEG (뇌전위) pattern: Fig. 6-16

Stage W: Waking: alpha waves (8-13 Hz), 뇌의 뒷부분에서 현저
Stage A: alpha waves ---> disintegrate, small theta waves (4-7 Hz)
transition from waking to sleeping
Stage B(1): lightest level of sleep, 제 1 단계 수면
theta waves
at the end of stage B---> large vertex sharp waves (3-5 sec dur)
심장박동률 감소, 근육 긴장 감소
Stage C(2): light sleep
beta spindles (sleep spindles), K complex
외적 자극에 대해 거의 무반응
Stage D(3): intermediate sleep
rapid delta waves (3.0-3.5 Hz)
Stage E(4): deep sleep, EEG is synchornized, 큰 진폭
maximally slowed delta waves (0.7-1.2 Hz), occaisonal alpha
Stage BCDE= NREM sleep, synchronized sleep, slow wave sleep (서파수면)

REM stage
desynchonized waves, resembling stage B
burst of rapid eye movement (급속한 안구운동), 각성시키기 매우 힘듬
---> by naked eye, electro-oculogram (EOG
rest of the musculature is practically atonic (근육이완)
bursts of brief twitches, 호흡, 심장박동 빠름
awakening threshold is about as high in REM sleep as in deep sleep
paradoxical sleep (역설적 수면), desynchonized sleep
dream occurs during REM sleep
Fig. 6-17:
a: 3-5 cycles/night, REM stage recur about every 1.5 hrs,
평균 1.5 시간의 cycle: 기본 휴식활동 주기 (basic rest-activity cycle)
각성중의 공상(daydreaming)도 약 100분 간격
duration average 20 min, increases in the course of the night
(처음 REM 기간은 불과 5-10 분, 깨어나기 직전: 40 분 정도 지속)
수면 초기의 주기들은 짧고, 3,4 단계의 서파수면이 많다.
body temperature: unaffected by the rhythmic fluctuations in depth of
sleep
e: heart rate, respiration: phasic fluctuations, pennis errection
especially apparent during REM sleep.

Fig. 6-18:
Age relation
reduction in total sleeping time, 모든 포유동물에서
생후 2주 까지: 50%가 REM 수면, 각성상태에서 바로 REM으로 이행가능
생후 16 주가되면 수면과 각성의 주기가 명백해진다.
decrease in the proportion of REM sleep
large proportion of REM sleep in very young children
---> importnat for the ontogenetic development of the CNS
짧은 평균시간, 빈번한 S/W cycle
5-6세 까지는 slow wave 수면의 특징적인 EEG이 불명확
노인: 3,4 단계 수면의 감소: 인지능력의 감소와 유관

Sleep and dreams

dream: NREM < REM
60-90% dream reports on waking from REM sleep
NREM: talking, sleepwalking, night terror of children
abstract, thought-like (cognitive), 사고적
REM : more lively, visual, and emotional, sensory (odrors, tones)
easier to recall
by no means a consequence of visual dream (unborn, newborn)

first half of the night: more closely related to reality
having to do with events of the preceding day
현실적 내용이 중심
second half of the night: less related to every day life
toward morning, bizarre, emotionally intense


Preceding events influences dreams
water deprivation--->
exciting movie or TV play before going to bed--->
increases duration and intensity of the REM phases
and the dreams
REM deprivation---> longer and deeper REM, more intense dream
---> no long-lasting physical or mental consequences
External stimuli during REM sleep
acoustic stimuli---> incorporated into dreams
time markers for the dream reports

Sleep, dream and memory
꿈의 기능: 수수께끼, 원시 문화 (꿈의 진실성 강조),
문제해결, 소원성취, 무기능
not retained unless alpha activity appears in the EEG during or
after the presentation
final dream before awaking is remembered.
Sleeping facilitates the consolidation of material to be learned
several possible reasons
a: less distracting events (방해자극의 감소)
b: passive forgeting process operates more slowly
c: active REM sleep makes a positive contribution


Sleep disorders
snoring: mouth open, tongue sunk back into the throat, supine
sleep apnea (수면성 무호흡): spontaneous interruption of breating
crib death (유아가 갑자기 죽는 증후)
grinding of the teeth: teeth sharpening, phylogenetically old
talking in one's sleep

Sleepwalking (somnambulism, 몽유병)
neither pathological symptom nor harmful
happen to at any age, but is most common in children and young
occurs in deep sleep
서파수면시(3,4단계 수면)에 많다, 성숙해지면서 사라짐

Bed-wetting (enuresis)
happens to about 10% of all children above the age of two
always occurs during NREM sleep
밤수면의 처음 1/3에 주로 (3,4단계 수면시)

Pavor nocturnus (night terror)
3-8 years old, rare after puberty, 비명
잠든지 약 1시간후에 나타남, 제4단계 수면시 주로

Sleep paralysis
absolutely impossible to make a movement
when waking up, falling asleep, fully coscious
suprising, often accopanied by frightening halucinations

Insomnia
수면의 시작과 지속의 장애
about 15% of all adults
subjective sleep deficiency
actually sleep more than they realize
as long as the insomnia does not involve distinct shortening
of total sleep duration for a long period---> no threat to health
정상인에 비해 더 적은 REM 수면, 더 많은 2 단계 수면

수면발작 (narcolepsy):
갑작스런 수면, 5-30분간 지속 (정상적인 일과 중에도)
근육긴장의 일시적 상실
막바로 REM 출현
뇌간의 기능장애
강한 정서자극에 의해


위궤양 환자: REM시 3-20배 위산 분비
심장병 환자: 사먕, 새벽 4-6시 (REM이 가장 강하고 지속적일때)


Waking/sleeping behavior of animals
REM sleep is a relatively recent development.
Fish(어류), 양서류, reptiles: no REM sleep
Birds: very brief (seconds), less than 1 %
검은제비갈매기: 활강중에 잠간 잠, 착륙하지않고 몇달 공중
Mammals: considerable time for REM sleep
hunting species: about 20%
hunted : 5-10%
몸집이 작은 소동물: 짧은 REM 기간, 짧은 수면 주기
(REM 수면: 체온 조절 불확실)


Mechanisms of Waking and Sleeping

1) Why must we sleep?
2) How does sleep begin?
3) Why and how does it end?
4) What mechansims are responsible for the various stages of sleep and
for the periodic transition from one stage to another?

A: conesquence of a decrease in wakefulness
passive envent
B: active termination of the waking state


Deafferentation theory of sleep
Fig. 6-19
1930, F. Bremer, EEG of cat brain
isolated brain (lesion at medulla)---> synchonized & desynchronized
waking patterns
isolated forebrain (lesion at midbrain)--->
elimination of all sensory stimuli except sight and smell
---> only a synchronized sleeping EEG

conclusion:1) activity of the CNS is induced and controlled primarily
by sensory stimuli.
2) waking state requires at least some minimal level of
cortical activity, maintained by sensory input
3) sleep is a condition induced and maintained by a reduction
or diminished effectiveness of sensory input.
Deafferentation
4) sleep induction is basically a passive phenomenon.

Opposition to deafferentaion theory:
1) in time the chronic isolated forebrain prepearation does develp
a sleeping/waking rhythm.
2) sensory deprivation causes a progressive decrease in the
duration of sleep during the period of isolation
3) organisms without the tel- and diencephalon show
sleeping/waking rhythm.

Reticular theory of waking and sleeping

Fig. 6-19C
late 1940's, G. Moruzzi and H.W. Magoun
brainstem reticular formation (RF): 뇌간의 망상체
high frequency stimulation---> immediate awakening
lesion---> permanent sleep
ARAS (ascending reticular activating system)
nonspecific projections
crucial arousal center

Opposition:
1) electrical stimulation---> both sleeping and arousal
2) neuronal activity: no correlation
3) isolated forebrain---> S/W rhythm
RF not soley responsible for waking and sleeping

Serotonergic theory of sleep

Fig. 6-19C
raphe nuclei: serotonin (5-HT)
M. Jouvet, late 1960's
cat, destruction of the raphe nuclei---> total insomina for several days
blocking the synthesis of 5-HT (with parachlorophenylalanine, PCPA)--->
partial loss of sleep
5-hydroxytryptophan (precursor of serotonin) 투여---> correction

locus coeruleus (noradrenalin)
bilateral destruction of LC---> complete abolition of REM
no effect on NREM
Reserpine 투여---> simultaneous exhaustion of the stores of
serotonin and noradrenalin
---> insomnia
subsequent 투여 of 5-hydroxytryptophan---> restores NREM only

conclusion: 1) release of serotonin causes active inhibition of the
the arousal systems---> induces sleep (NREM)
2) REM sleep by LC
3) LC inhibits raphe N---> initiation of awakening

this theory is no longer tenable in its original form
raphe neurons: most active in arousal rather than in sleep
REM activation seems to be due less to the neurons of the LC than
to those of the more diffusely distributed nucleus subcoeruleus
but 5-HT: promoting the synthesis or release of sleep substances

Endogenous sleep factors
1) sleep factor(s) would accumulate during the waking state
Factor S (a small glucopeptide from urine or cerebrospinal fluid)
---> induces NREM sleep
REM-sleep factor
2) sleep promoting substances are produced or released during sleep
DSIP (delta sleep inducing peptide, nonapeptide)

not known what role they play in the physiological control of sleep


Biological functions of sleep (수면의 생물학적 기능)

증명된것 무
no satisfactory answer to the question of why we must sleep
1) Serving recovery: little experimental support
a) physical exertion ---> causes to fall asleep
no change of the duration of sleep
수면전 신체운동--> 전체 수면시간의 무변동
b) people with extremely little sleep
말: 2 시간/하루,
standford 대의 한 교수: 50년 이상 3-4 시간/하루 ---80세
c) no explanation for the existence of REM and NREM sleep
2) 에너지 보존: 수면시 에너지 소비감소
(근육긴장, 심장박동, 혈압, 호흡, 신진대사등의 감소)
문제점: REM sleep
3) 포획동물로 부터의 회피: 생태적인 적소에서, REM 수면은 주기적 유사각성
4) 정보처리를 도운다: 하루동안의 기억을 분류하고 강화하는 기능










BRAIN FACTS

6.4 Neurophysiological Correlates of Consciousness and Speech


Consciousness : from sleep, anesthesia, coma, or severe concussion
experienced introspectively
essential feature of our existence
physiological and psychological research object

Phylogeny of consciousness
impossible to draw a sharp dividing line between animals
with consciousness and those without
consciousness seems to develop roughly in parallel with
the phylogenetic development of the nervous system
Animal kingdom comprises many gradations and extremely varied
forms of consciousness.

Functional and Structural Prerequisites for Consciousness; Role of the Hemispheres

Excessive neuronal activity---> epileptic seizure
Too little neuronal activity---> coma, anesthesia
Intermediate activity level---> consciousness
적절한 정도의 Activity-dependent 막 흥분성의 변화===> 의식

Interplay of cortical and subcortical structures에 의해

Split-brain patients: corpus callosum과 anterior commisure를 절단
epileptic activity의 spread를 막기위해
Fig. 6-20, inconspicuous in everyday life
intellect unchanged
left cerebrum---> right motor & somatosensory
left hemisphere---> right visual field (optic chiasm)
left auditory cortex---> both sides
R. Sperry et al., Fig. 6-21, tachistoscope
visual and tactile stimuli on the right
---> to the left brain

a) object on the right visual field, word
---> name it, pick it with right hand
---> write it down with right hand

b) object (word) into the left half of the visual field
---> cannot name it (but perceive, learn, remember,명령)
---> pick it out with the left hand
---> cannot express what he is doing
two indenpendent minds
a) left under the control of consciousness
b) rightly largely functioning uncousciously and automatic

Conclusion:
left hemisphere: language & speech
cause interpreter (reudcing cognitive dissonance)
analytical, sequential processing
right hemisphere: visual & tactile form recognition
abstraction, speech comprehension
indentification of faces (Fig. 6-22)
spatial conceptualization
musical tasks, simple linguistic input
parallel processing
Intact normal person: 2 hemisphere의 specialized function을
분리하기 힘들다. aid one another

sodium amytal (a fast-acting barbiturate)를 internal carotid artery
lesions of the right hemisphere
----> emotionally indifferent, euphorically disinhibited
lesions of the left hemisphere
----> catastrophe reactions with deep depression
lateralization of the mood
lesion on one side ----> causes overexcitation of the other side
(disinhibition)

Why is function laterized to one hemisphere?
a) inherent anatomical asymmetry in the human brain
present even in human fetus.
b) functions that require extensive intracortical
connectivity: corpus callosum은 상대적으로 적다.
great apes, monkeys, rats, cats, birds에도 lateralization 유

Neurophysiological Aspects of Language and Speech

Four Features of Language

Creativity
Form (Phonemes)---dysarthria (소뇌의 손상에 의해 발음 불분명)
---Broca's aphasia (cerebral cortex의 lesion)
Content (Morphology, Grammar)---Wernicke's aphasia, conduction aphasia
Use (social communication)---aprosodias, schizophrenia
Animal Language

Cricket, Bees, Birds.... natural language.
..form,content,use,creativity are highly stereotyped
Chimpanzee를 집에서 기름---never learned to speak
sign language: up to 160 words 배움 (4살 인간: 3000이상)
no understanding of syntax
Origin of Human Language
10만년 전에 갑자기 나타났다, left temporal lobe의 발달은 50만년 전
Gestural theories: 원숭이가 일어서서 손으로 의사표시
Vocal theories: 손을 딴 목적에 쓰고 입으로 의사표시

언어능력은 innate process
a) localizabel to one hemisphere
b) anatomical difference (planum temporale)
c) 31st week of gestation시 해부학적 차이
d) infants at birth: 여러 소리에 민감
f) stages development in the acquisition of language가 all culture에서 동일
brain development와 밀접

Lateralization of language and speech

right-handed people: Left hemisphere is dominant hemisphere for
language and speech
left-handed people: right hemisphere is generally dominant for
language and speech functions
sometimes left hemisphere, or bilateral

Speech and language areas

Brocas's speech region (Fig. 6-23A)
motor aphasia, lower part of the third frontal gyrus on the left
immediately in front of the parts of the motor cortex that control
the muscles of the face, jaws, tongue, palate and throat
(muscles necessar for articulation)
---> great effort, short sentences, reduced to the most
essential nouns, verbs and adjectives

Wernicke's speech region (Sensory Aphasia)
posterior part of the first temporal lobes, in the immediate vicinity
of the auditory cortex
deficit in understanding of language
speech fluent

Tertiary speech region (overlapping roughly with the MII)
Penfield, electrical stimulation
---> aphasia for the duration of stimulation
---> no elicitation of words or sentences

lateral precentral gyrus의 자극---> vocalization

language functions are lateralized to one hemisphere
articulation, the execution of speech are bilateral

prosodic aspects of speech (accentuation, intonation): right hemisphere

Wernicke-Geschwind model of language
Fig. 6-24A
Visual information from retina--->primary visual cortex (area 17)
---> area 18 (higher visual area)
---> association cortex (area 39), shape recognition
---> area 22 (Wernicke region): (receptive) word finding; sensory aphasia
---> arcuate fasciculus; conduction aphasia (resemble sensory aphasia)
---> Broca's region: (expressive) forming of speech; motor aphasia
---> motor cortex: articulation (vocaliztion)

Global aphasia: both Wernicke's & Broca's area damage
(supplied by the middle cerebral artery)
amnesic aphasia: disturbances in the temporal-parietal association cortex
---> disturbances in word-finding ability
alexia (reading, sensory); agraphia (writing); acalculia (arithmetic)

Language and action
Fig. 6-24 B
Verbal command (lift the right hand)
---> auditory cortex
--> Wernicke's region for interpretation
---> arcuate fasciculus
---> left associative premotor cortex (design for the action)
---> left primary motor cortex (execution of the movement)

Fig. 6-24 C
Verbal command (lift the left hand)
---> auditory cortex---Wernicke-->assoc pre motor ctx
(corpus callosum)---> right pre motor ctx ---> right MI ctx


6.5 Plasticity, Learning, Memory


Forms of Learning and Memory


Biological significance and extent of information storage

Learning:intake,
밖으로 부터의 정보와 지식을 획득하는 과정
Memory:storage, 정보의 유지와 저장
and retrieval
basis of adaptation of individual behavior to the environment
selective storage, forgetting

학습의 연구: 행위의 변화를 보아,
direct examination of the brain (행위의 변화가 없는 학습시)

Habituation and sensitization (non-associative learning)

2가지 주된 학습형태:
nonassocaitive learning: 한 종류의 자극에 동물을 한번 또는 반복 노출 시킬 때
---> 동물이 자극의 성질에 대해 배울 수있는 기회 제공
associative learning:
a) 한 자극과 다른 자극과의 상관관계를 배움---> classical conditioning
b) 한 자극과 동물의 행동과의 상관관계를 ---> operant conditioning
(instrumental)

2 가지의 nonassociative learning: Habituation & Sensitization

반복된 자극에 대한 orienting response가 사라짐: e.g.,큰 소리로 놀라게
habituation: accomodation to a repeated stimulus that the organism
recognizes as unimportant

: most widespread form of learning in humans and animals
----> turn our attention to more important events
----> stimulus specific
----> not a matter of fatigue
----> independent adjustment process
----> X adaptation ( increase in threshold of a sense organ
exposed to continuous stimulation)


Sensitization:
increase in a physiological or behavioral reaction to stimuli
---> stimulus and situation specific
자극: 주로 강하거나, noxious

complex nonassociative learning:
sensory learning: continuous record of sensory experience
imitative learning: acquisition of language

Behavioral memory and knowledge memory

conditioning---> behavioral memory (reflexive memory, animal)
reflexive memory: automatic or reflexive quality
its formation or readout is not dependent on
awareness, consciousness, or cognitive processes
expressed primarily by improved performance
Perceptual and motor skills & the learning of procedures and rules

cognitive process---> knowledge memory (declarative memory, human)
declarative memory:
depends on conscious reflection for its acquisition & reacall.
relies on cognitive processes such as evaluation, comparison, inference.

associative learning: association b/w stimuli (S) & responses (R)
habituation & sensitization: non-associative learning


Behavioral Memory (Learning by Conditioning)


Classical conditioning

Sherrington's concept of the "reflex act" +
John Locke, Aristotle의 학습:"association of ideas"
classical conditioning (by Pavlov)===> idea에 대한 객관적 연구
flexor reflex: unconditioned reflex (UR)
conditioned reflex (acquired reflex) (CR)


US(unconditioned stimulus): food ---> UR(unconditioned response)
항상 분명한 행위의 변화 유발
CS(conditioned stimulus): bell sound
2가지: appetitive, defensive
CS->US->UR becomes CS-> CR(conditioned response)
association(pairing) of two stimuli
환경내의 사건 사이의 관계를 예측함을 배운다.
동물의 perceptual capacity를 조사할 수 있다.
extinction: CS에 의해 CR이 형성된 후 시간이 지남에 따라
CR의 강도와 빈도가 낮아지는 현상
---> 이미 학습된 것이 단순히 사라지는 것이 아님,
CS가 US의 발생하지 않음을 예측
CS와 US 사이에 contiguity(인접성)와 contingency(우연성)이 있을때
classical conditioning이 가장 잘 일어남.
prey VS predator의 인식, nutritious food VS posionous food
이러한 것들의 구별은 genetical preprograming 또는 학습에 의해 가능

conditioned reflex is learned passively
involved in the development of autonomic reactions
less role in the acquisition of motor responses

imprinting: special form of associative learning
based on an innate prediction for particular S-R 조합


Operant (instrumental) conditioning : trial-and-error learning

animal can acquire new behavior actively
배고픈 쥐의 여러 행위 중 bar pressing behavior의 증가-->food
자신의 행동의 결과를 예측함을 배움

response to be learned is followed immediately
by a rewarding or punishing stimulus.
(positive or negative reinforcement of the behavior)

Skinner boxes (Fig. 6-25)

similarity b/w instrumental and classical conditioning
---> optimal time interval b/w the critical events
is 500 ms in both cases.

difference: operant conditoning requires more complex
neural networks
classical conditioning: restricted to specific reflex

brain is not a tabula rasa, but is iherently predisposed to
detect and manipulate certain environmenatal contingencies.

associate stimuli that are relevant to their survival
e.g. food aversion (bait shyness)---> treatment of chronic EtOH
therapeutic technique: systematic desensitization (extinction)
psychiatry, decrease neurotic anxiety or phobias
operant conditioning: in the management of severely disturbed
institutionalized patientis with behavioral problems.
biofeedback: stroke patient의 작은 근육의 움직임 기록--> cue


Learning in the autonomic nervous system

classical conditioning뿐만 아니라
operant conditioning도 가능
---> long-term changes in heart rate,
the tone of the intestinal musculature등등


Knowledge Memory (Cognitive Learning)

4 generalizations on the neurobiology of memory
1) memory has stages and is continually changing
2) long-term memory may be represented by physical (plastic) changes in 뇌
3) the physical changes coding memory are localized in multiple regions
4) relexive and declarative memories may involve different neuronal circuits


Fig. 6-26
short-term memory
long-term memory: consolidation에 의해 engram(moemory trace)이 형성됨


Input---> STM(PM)--->LTM(SM+TM)
Search & Read-out ----> Output

Table 6-1
Sensory memory (very brief short-term memory)
stored automatically, for a few hundred ms
fading and extinction
auditory (echoic),
visual (iconic memory):
photochemical processes in the retina (visual afterimage)
actively extinguished, or written over by information taken up later
tranfer to a more permanent memory (via either verbal or nonverbal coding)
encoded by a transient physical change in the sensory receptor

Primary memory (short-term memory)
serves for the temporary storage of verbally coded materials.
smaller capacity than sensory memory
stored in the order of its arrival time
forgetting: replacing by new items
duration: seconds
only verbal memory
nonverbally coded sensory memory---> secondary memory
transfer to secondary memory: by practice

Secondary memory
large long-term storage system
capacity?, duration?
inforamtion is stored according to its significance
organization: confusion between similarly significant words
slower retrieval than primary memory
forgetting: proactive (interference by previously learned things): 중요
retroactive (interference by subsequently learned)

Tertiary memory

never forgotten
extremely short access times
possible that they are simply very well consolidated engrams
in the secondary memory.

long-term memory= secondary+tertiary memory
even without external trauma, there is a gradual loss of
the stored information or a diminished capacity to retrieve it.
---> memory process은 시간에 따라 계속 변화
memory process is also subject to modification
when the memory is first formed.

Disturbances of Memory


Anterograde amnesia (amnestic syndrome or Korsakoff's disease)

: inability to learn newly acquired information
cannot transfer information from the primary to the secondary memory
clinically called "recent memory"
caused in particular by bilateral damage to or removal of the
hippocampus and the sturctures associated with it.
---> a key role in the recording and transfer of information
from the primary to the secondary memory (selection)

Fig. 6-27A: 복잡한것은 기억 불가
particularly severe where declarative tasks are concerned
less pronounced for procedural learning (usually nonverbal)


Retrograde amnesia

inability to retrieve items stored in memory in the time
before normal brain function was impared.

possible causes: mechanical shocks (concussion)
stroke (apoplexy), electroshock (therapeutic or by 사고)
----> associated with fairly generalized disruption of brain fx.
----> not yet known which particular structural and functional
disturbances give rise to retrograde amnesia.
erases the content of the primary memory
interference with access to the secondary memory
read-out of recent memories is easily disrupted.
tertiary memory is unaffected


Hysterical amnesia










BRAIN FACTS



Neuronal Mechanisms of Plasticity and of the Engram


learning and memory: the most obvious signs of the life-long
modifiability and plasticity of the nervous system

search for the structural, physiological and biochemical bases of 가소성
Plasticity is only a prerequisite for learning, retention and recall.

Habituation and sensitization

Simple forms of learning (habituation, sensitization, classical condit.)
---> synaptic transmission의 효율성의 변화 (plastic changes)

Habituation: Depression of Synaptic Transmission
a reduction of the release of presynaptic transmitter

Sensitization: Enhancement of Synaptic Transmission

long-term habituation and sensitization-->structural alteration of the synapses
---> decrease or increase in the number and size of the presynaptic active zones

changes in synaptic efficiency due to use and non-use have long been
regarded as one of the bases of the essential bases of 신경가소성
eg. posttetanic potentiation at certain excitatory synapses (hippocampus)
visual cortex, if not used---> histological & functional signs of
degeneration
---> considerable hypertrophy
cerebellum: simultaneous activation of the synapses
of mossy and climbing fibers on a Purkinje cells.


Engrams of the behavioral memory

classical conditioning in simple nervous system (sea slug Aplysia)
---> presynaptic facilitation involved in the learning process
---> associative learning can be ascribable to the activity of a few neurons
---> many learning processes that produce engrams in the behavioral
memory cannot be explained without invoking complex neuronal networks

Classical conditioning involves an Associative Enhancement of
presynaptic facilitation that is dependent on activity.
CS---0.5sec---US--->CR: timing is critical
convergence of CS & US in individual sensory neuron
Activity-dependent presynaptic facilitation
modulation of K+ channel
Ca+2/calmodulin에 의한 adenylyl cyclase의 자극
---> cAMP의 증가---> cAMP-dependent protein kinase
---> 다량의 neurotransmitter 분비

Engrams of the knowledge memory

simplest and most intuitively appealing idea about the neuronal
basis of cognitive learning:
---> information stored in the form of an orderly spatiotemporal pattern
of reverberating excitation. (dynamic engram) (practice)
deep anesthesia, anoxia, cooling---> silencing of neuronal activity
===> short-term or recent memories are disrupted
dynamic engram---> brings about structural changes at the synapses
(consolidation to a structural engram)
retrieval by corresponding activation of these synapses.

locaization of the engram:
Pavlov는 국재적으로 믿음, Lashley---> lesion study---> 실패
almost all regions of the brain have a potential memory function
memory trace is not laid down in a spatially circumscribed area
simple reflexive memory by spinal cord
simple leraning task: several parallel channels of
information are used (parallel processing).
many ways for information to be stored in different regions of 뇌
capability to reconstruct the original memory from the limited 정보
different memory processes require different, clearly distinguishable
brain regions.
reflexive memory: locaizable
e.g. lesion of the amygdala---> interfere w/h conditioned heart rate responses
nictitating membrane response---> abolished by lesion in cerebellum

declarative memory: affected by lesions of the temporal lobe or
of the diencephalon
---> interfere primarily with the retention of new memories
temporal lobe, diencephalon: are not for memory storage
temporal lobe의 전기자극:---> melody 기억, amnesia
Hippocampus의 lesion---> anterograde amnesia, STM intact


Neurochemical Mechanisms of Plasticity and of the Engram


genetic memory: DNA
immunological memory
a crucial role of protein biosynthesis in consolidation

inhibition of protein biosynthesis (by puromycin, cycloheximide, anisomycin)
---> interfere with the formation of a structural engram in the cell or cell 막
---> prevention of permanent memory.
---> the most pronounced amnesia is achieved when protein synthesis
is inhibited shortly before the beginning of a training session
--->no protein synthesis during training
protein synthesis is necessary only for a critical consolidation phase
during and shortly after training

inhibition of protein synthesis does not interfere with the short-term memory
---> different mode of operation of short-term and long-term memory.
STM---> covalent modification of pre-existing proteins
---> cAMP-dependent protein kinase
---> K+ channel을 phosphorylation
---> N-type Ca2+ 채널이 오래도록 활성화 됨
---> transmitter release 가 많아짐
transmitter mobilization을 활성화
----> L-type Ca 채널의 변화
----> transmitter vesicle의 쉽게 이용 되도록
LTM---> synthesis of new protein and mRNA
--->cAMP-dependent transcriptional regulator proteins의 phosphorylation
---> cAMP-dependent protein kinase의 지속적인 활성화
---> synaptic connection의 성장
morphological change(growth, regression, pruning)

still not possible to achieve a direct, specific improvement of
intelligence and of learning and memory performance by pharmacological means.


Hippocampus: important for storage of declarative memory
Pathwasy:
Perforant fiber pathway----> granule cells of the dentate gyrus-->
mossy fiber pathways---> pyramidal cells in the CA3 region--->
Schaeffer collateral fiber pathway---> pyramidal cells in CA1

LTP (lon-term potentiation)
brief high-frequency stimulation to any of the three afferent 경로
---> increase in the excitatory synaptic potential in the
postsynaptic hippocampal neurons (last for hours)
LTP in the CA1 region
1) cooperative (하나 이상의 fiber가 활성화 되어야)
2) associative (fiber와 postsynaptic cell이 같이 active해야)
NMDA receptor의 활성화--->influx of Na+ & Ca2+
NMDA receptor: doubly gated channel
normally blocked by Mg2+, Glutamate+depolarization
depolarization by non-NMDA receptor에 의해
Ca2+---> Ca2+/calmodulin kinase와 protein kinase C를
활성화
LTP의 유지: presynsptic transmitter의 분비
retrograde plasticity factor
3) specificity (specific to the active pathway)

LTP in the CA3 region: nonassociative
NMDA receptor의 antagonist인 APV (aminophosphonovalerate)에
의해 block이 안됨,
does not require Ca2+ influx



6.6 Functions of the Frontal Lobes

prefrontal cortex (frontal granular cortex)
nonhuman primates와 사람에서 큰 volume 차지
1) prefrontal association cortex: areas 9 to 12:
dorsal and lateral surfaces of the FL
2) orbitofrontal cortex: areas 13 and 14 on the orbital surface
part of the limbic association cortex

afferent: dorsomedial nucleus
limbic systems (reciprocal): cingulate gyrus, hippocampus
amygdala and the hypothalamus

neocortical part of the limbic system

dorsal components linked to the hippocampus
ventral components linked to the amygdala

prominent dopaminergic innervation

future action들에 대한 결과의 예상 및 future action의 계획


limbic system plays a special role in the species specific behavior
(motivation, drives)

prefrontal cortex: learned control of innate behavior patterns

Inferences from frontal-lobe lesions in humans

frontal-lobe lesion
---> normal on intelligence tests
---> subtle personality changes
lack of motivation, absence of firm intensions
absence of plans based on foresight
unreliable, crude, frivolous

Schizophrenics (정신분열증 환자):
smaller frontal lobe

Fig. 6-29: perseveration : persistance of motor act which has begun
dissociation between verbal and other motor reactions
차 운전 시: 왼쪽 말에---> 오른쪽으로 감
impression that the preceding memory trace cannot make room for the next
rapidly enough---> an enhanced proactive inhibition

conscious of their mistakes, but incapable of bringing
their impulsive actions under control.

prefrontal cortex is involved in the learned control of inborn behavior
patterns and in harmonizing external and internal motivations.
Frontal-lobe symptoms in animal experiments
tendency to perseveration
poor scores on the tasks with delayed reinforcement
increased distractability

prefrontal cortex: development of behavioral strategies










BRAIN FACTS