Higher

Func,on – Human Brain

dr. Alya Dwiana, MSc

 REFERENSI

•  Bob Garret. Brain & Behavior. 4th Ed

•  Dale Purves. Neuroscience. 5th Ed.
 OCCIPITAL LOBE :
VISION – PLACE, OBJECT & FACE RECOGNITION

Ref: Purves Neuroscience chapter 12

Contra-lateral division of
labor

•  Right hemisphere
controls leG side of body
and visual field

•  LeG hemisphere controls
right side of body and
visual field
 The Visual Pathway
Transmission of visual
informa,on to the brain.
•  Re,na
•  Op,c nerve
•  Lateral Geniculate
Nucleus (LGN)
•  Op,c radia,ons
•  Visual cortex
 Target of Ganglion cells axons
1.  Lateral geniculate nucleus (thalamus)
-  Major target of most GCs
-  Visual pathway
2. Pretectum (midbrain)
-  Pupil responses
3. Suprachiasma,c nucleus (hypothalamus)
- Circadian rhythm
4.  Superior colliculus
- Eye movements
5.  Other : various nuclei of thalamus
- Photophobia
 The Primary Visual Cortex (V1)
•  LGN neurons project to
the primary visual cortex
-  Area 17
-  Occipital lobe around the
calcarine fissure
•  Each half of the visual
field is represented on
the contralateral visual
cortex
•  Re,notropic organiza,on:
neighbouring cells within
the re,na project to
neighbouring cells in the
LGN and visual cortex
(From fig.27-9 Kandel et al 2000)
 Intrinsically photosensiFve ganglion
cells
•  A small popula,on of GCs
contain a visual pigment
named melanopsin.
•  Melanopsin is similar to
visual pigments found in
invertebrates.
•  Light ac,va,on of
melanopsin leads to
depolariza,on of ipGCs.
•  There are mul,ple types
of ipGCs.
ipGCs à funcFons: Circadian rhythm
 ipGCs and Circadian rhythm

•  In blind people,
melatonin levels are
suppressed by light (like
sighted people)
•  Ac,vity and sleep in the
blind people is not
disturbed.
ipGCs project to the
hypothalamus.

Suprachiasma,c nucleus
(SCN) is a small nucleus
within the hypothalamus
that is important for
driving circadian rhythm.

ipGCs project to the SCN of
hypothalamus.
 Two parallel visual streams
•  Dorsal pathway (“Where”)
-  Mid temporal lobe is
important for detec,ng
where an object is.
-  Links with motor system.

•  Ventral pathway (“What”)
-  Inferior temporal lobe is the
center for object
recogni,on
-  Visual processing via V1, V2,
V4 and IT
-  Anterior and posterior
subdivisions of the inferior
temporal lobe.
 Strokes and Object RecogniFon

•  Strokes gave first clues on importance of

ventral temporal lobe.
•  Strokes give two extreme types of problems
with object recogni,on.
•  Both lead to agnosia (“ignorance” or “absence
of knowledge”)
 Object Agnosia
•  Although visual acuity is intact.

•  AppercepFve agnosia:
-  Can describe objects and their func,on from memory
-  Can iden,fy objects by touch
-  Can’t copy drawing of object
-  Can’t see object. See assemblage of parts.

•  AssociaFve agnosia:
-  Can describe objects and their func,on from memory
-  Can’t iden,fy by touch (?)
-  Can copy drawing of object
-  Can “see” object as object, but can’t name it.
 Object recogniFon in the temporal lobe

Can copy but

Knows the
cannot tell
object but
the name of
cannot copy
the object
 CriFcal Temporal Lobe Structures
•  AppercepFve Agnosia
= damage to first stage of object recogni,on (in
posterior inf. temporal lobe)


•  AssociaFve Agnosia
= damage to second stage of object recogni,on (in
anterior inf. temporal lobe)
 Vision and Memory
•  Object recogni,on is
associated with visual
categoriza,on, visual
memory and emo,on.

•  Range of outputs from
inferior temporal lobe
-  Perirhinal and
parahippocampal
cor,ces
-  Prefrontal cortex
 Vision and Memory

•  Visual experience influences the processing of

incoming visual informa,on.
•  Neurons in the inferior temporal lobe can be
modified by experience.
 Vision and Short-term Memory
•  Neurons in prefrontal
cortex and inferior
temporal cortex
con,nuously fire even
aGer the visual image
has been removed.
•  This con,nual firing is
thought to be
important for
maintaining short term
memories.
 The Dorsal Stream

•  “Where” pathway
•  V1, V3, MT, parietal lobe
•  Links with motor system
 The Dorsal Stream: area MT

•  Area MT: middle

temporal lobe is an area
specialized for processing
object mo,on.
-  Receives re,notopic
informa,on from a
number of cor,cal
areas including V2 and
V3.
-  Receives input from
cells in layer IVB of the
primary visual cortex
Dorsal vs Ventral Stream
 Face recogniFon
•  Face oGen used as s,mulus for vision tasks.
•  Faces à a powerful s,mulus, because faces
very important to primates.
•  Iden,fy individuals, convey emo,on and other
informa,on.
•  Face recogni,on can be selec,vely affected by
strokes (prosopagnosia).
•  Can recognize that it is a face, but not who it
belongs to. Can recognize voice.
 Prosopagnosia
•  Strokes producing prosopagnosia
involve fusiform and lingual gyrus
in inferior temporal lobe.
•  Subset of object recogni,on areas.
•  Damage usually bilateral, but
some cases with right side damage
only.
•  Subset of object specific agnosias
(alexia, some other object classes
reported).
 Developmental Prosopagnosia
•  Some people born with prosopagnosia
•  Have completely normal vision
•  OGen face recogni,on only deficit, normal
object recogni,on
•  “Face recogni,on a specific type of object
recogni,on with dedicated neural circuitry?”
•  However, developmental and induced
prosopagnosia can “spill over” into general
object recogni,on deficits
 Fusiform Face Area
•  Some studies localize face
recogni,on to a small
area of the temporal lobe
(fusiform face area)
•  Fits into a specific part of
the object recogni,on
network
•  Humans and Macaques
have five other areas in
addi,on to FFA that
respond to faces
•  Damage to any one can
cause forms of
prosopagnosia
 Role of MulFple Face Areas
•  Each face responsive region does a different thing
1.  Iden,fies “faces” from one direc,on
2.  Generalises across mirror images (“b” and “d”)
3.  Unites various views of individual face
(invariance)
 Other Object RecogniFon Areas
•  Tend to be in reproducible places
•  Body parts – “extrastriate body area” – lateral
occipito temporal area (also addi,onal region,
“fusiform body area”)
•  Places/landmarks – “parahippocampal place
area” – loss leads to landmark agnosia
•  Words – “visual word form area” leG inferior
temporal lobe – loss leads to alexia
 Case Study
•  Female, 70 years old
•  Sudden onset headaches, right sided weakness, visual loss
•  Following morning found to be totally blind
•  Although she said she couldn’t see, she accurately reached
out to shake hands and could feed herself
•  Said everything seemed to “run together”
•  Physical Examina,on:
-  Able to see and point to objects presented visually
-  Visual acuity was 6/30; visual field defect
•  PET scan: defects in inferior temporal lobe on leG side;
deficits on the posterior half of the middle temporal lobe
on R and L side
 Blindsight
•  Aware of the object although totally blind (no
primary visual cortex)
Alterna,ve routes of visual informa,on

LGN provides direct input to MT

The blind woman who saw rain
Prosopagnosia & Agnosia
 BRAIN AREAS involved in LANGUAGE

Ref: Purves Neuroscience chapter 27

 Language and Neuroscience
•  Language is the most accessible higher
func,on

•  Much work has been done to understand

where in the brain language ability resides

•  Insight depend on strokes (ini,ally) and fMRI

(more recently)
 What is Language?
•  Auditory, visual, or tac,le symbols for
communica,on

•  Has a grammar and lexicon (an arbitrary

meaning for each element)
 What funcFons must a hypotheFcal
language network do?
•  Must be able to detect and to generate:
-  Phonemes
= dis,nct sounds that make up words (“p”, “b”). 42 in english (25
consonants & 17 vowels)

-  Words
= objects, concepts, ac,ons, proper,es and logical connec,ves

-  Sentences
= complexes of words whose rela,onships determine meaning
(syntax)

-  Discourse
= higher order structure made of sentences
 Capacity of the language network is
amazing

•  Novel, complex informa,on easily conveyed

and understood

•  Knowledge of mul,ple languages possible

•  Acquired as a child when motor and cogni,ve

performance very immature
 Language acquisiFon
•  Innate, effortless, unconscious (no need to teach)
- 10 words – 13 months old
- 50 words – 17 months old
- 300 words – 24 months old

•  Rate of acquisi,on
- early à 1-3 words/week
- aGer 40 words or so, 8-10 words/week

•  Preschool and primary school – 10 words a day (1 word

every 2.5 hours)
•  Average adult vocabulary 40.000 – 70.000?
à 2 words a day for every day of your life.
 What do infants hear?

•  Foreign language sounds and structure hard

for an adult

•  Infants (< 1 year old) can detect the structure

and sound of all language equally
 Language acquisiFon experiment
•  Second half of first year à cri,cal
•  Expose 9 months US infants to Mandarin
(either via person or TV) for 1 month
•  Performance iden,cal with children raised
from birth in Mandarin, but only for personal
interac,on
•  Prior to 7 months à treat all languages as
equal
•  Between 7-11 months, specialize in language
that is in environment.
 Motor Pa\erns

•  Speech produc,on develops before language

understanding
•  All infants sound the same ini,ally – language
specific sounds by two years
•  Speech motor paperns are laid down at this
stage and are permanent (accents)
 CriFcal Periods
•  Adults smarter than infants, but infants much
beper at learning a language
•  Two or three languages easily learnt during
cri,cal period early in life
•  Ability to acquire a second language declines with
age, most rapidly at puberty
•  Exis,ng language interferes with acquisi,on of
new language
•  Hearing and speech neural pathways become
specialized for one language, not plas,c and
cannot adapt easily to another
 CharacterisFcs of Neural Pathways
underlying language
1.  Language processors highly specialised and
separate to rest of auditory pathways
2.  “On” permanently. Cannot choose to hear
language as just noise
3.  Operate unconsciously
4.  Incredibly fast – recognise individual words in
less than 125 ms (while they are s,ll being
spoken) – massively parallel
5.  Develops automa,cally – doesn’t require
“learning”
 AddiFonal Language Areas
•  Broca’s and Wernicke’s aphasias do not iden,fy all
cri,cal areas for language
•  Damage to leG temporal cortex:
-  Broadmann areas 20,21 and 38 à severe and pure
naming deficits (can’t retrieve words but no other
deficit)
-  38 only à loses names of unique places and people
but not common things
-  Damage to leG posterior inferio-temporal cortex à
loss of par,cular types of things (i.e tools &
utensils), but not natural things or unique en,,es
-  Damage to outside of leG temporal lobe à lost
ac,on words
 Where are the language circuits?
•  Classical series of regions associated with language
comprehension and produc,on
 Effect of Stroke
Broca’s Lesion (motor or Wernicke’s Lesion (sensory or
expressive aphasia) recepFve aphasia)
•  Speech non-fluent, •  Speech is fluent and
telegraphic, agramma,cal gramma,cal
•  Search for words •  Prolific (produc,ve)
•  Mainly use content words •  Content does not make
(adjec,ves, nouns and sense
verbs), few func,on words •  Paraphrasic errors (words
(ar,cles, pronouns, and sound incorrectly
conjunc,on) subs,tued)
•  Comprehension of simple •  Comprehension profoundly
sentences = OK, complex affected
sentences = poor
 Wernicke-Geschwind Hypothesis
•  Broca’s aphasia represents damage to output side,
grammar and word selec,on is disturbed.
(Paul Broca – “On parle avec l’hemisphere gauche” à we speak
with our leG brain)

à Broca’s aphasia must be specifically dis,nguished from
dysarthria (the inability to properly move the muscles of the
mouth, tongue and pharynx that mediate speaking)

•  Wernicke’s aphasia represents damage to input

side, comprehension is disturbed
 Wernicke-Geschwind Hypothesis

•  Lesion restricted to pure Broca’s or

Wernicke’s area have mild symptoms
•  Need to involve surrounding cortex to get full
symptoms
•  Subcor,cal regions (thalamus and caudate)
may also be important

à Hypothesis is useful, but over-simplified
 Cerebellum and Language
•  Cerebellum mainly
thought to have a
motor role in language
– seen in ataxic
dysarthria
•  Poor produc,on of
vowels and consonants,
problems with stress
and voice quality
 Cerebellum and Language
•  More than speech ar,cula,on affected
•  Word retrieval depressed aGer cerebellar
damage
•  Syntax impaired
•  Error checking impaired (like motor role of
cerebellum)
•  Other cogni,ve processes affected as well
•  Right hemisphere damage the worst
 Where else is the textbook wrong?
•  May also have to modify our view of lateralisa,on of
language
•  Usually stated that language depends on leG side of the
brain
•  Le7 Hemisphere – “dominant, verbal, analy,c and
intelligent”
•  Right Hemisphere = “non-dominant, nonverbal, visuo-
spa,al, holis,c and crea,ve”

•  Most people understand language and speak very much

beper with the leG hemisphere than the right. The
contribu,ons of the two hemispheres to the overall goals
of communica,on are different (correc,on to Broca’s
conclusion).
 Laterality of language
•  90% of people are right-handed, controlled by
dominant leG hemisphere
•  Centered in leG hemisphere in 96% of right-
handers; 70% of leG-handers (= 93% of
everyone)
•  Other leG-handers, in both hemispheres, only
rarely in right
•  Probability of right hemisphere language
dominance propor,onal to degree of leG-
handedness
 What contribuFon does the right (non-
dominant) hemisphere make to language?

•  Language facility is divided between

hemispheres, with different func,ons in each
hemisphere
•  Important, but needs sophis,cated tes,ng to
reveal deficits aGer lesion
•  The ability to produce and comprehend
complex language is in leE hemisphere
 What language tasks can right-
hemisphere (RHS) do?
•  Can read and understand numbers, lepers, short
words. Has a rich lexicon and can understand
propor,onal speech. But …………..
•  Can’t produce propor,onal speech. Can point to
objects shown to leG visual field or spoken into
right ear but cannot speak their name
•  Can produce non-propor,onal speech (days of
the week, nursery rhymes, coun,ng, swearing)
•  Iden,fies known words by direct recogni,on, not
phonology, beper at concrete words, not
abstract (“image-ability” important)
 What language tasks can right-
hemisphere (RHS) do?
•  Interpret and produce prosody – tone or
emo,onal content of speech
•  Interpret metaphors (non-literal language) à
stroke to RHS can lead to literal interpreta,on
of metaphor
•  Interpret humor
•  Interpret non-verbal sounds
•  No understanding of syntax
 BRAIN: WAKE/SLEEP areas

Ref: Purves Neuroscience chapter 28 & Garret’s Brain & Behavior chapter 15.
 Circadian Rhythms and Behavior
•  Organism are adapted to be ac,ve at a par,cular
,me of the day/night cycle (their circadian
rhythm)
à (la,n) circa = approximately, dia = day
•  Humans = day ,me, rats = night ,me
•  How do animals know what ,me it is?
•  Could track light cycle
•  What happens when you remove all clues (i.e live
in a cave)?
 Free running circadian rhythms
•  In a cave without external
clues (clocks, window,
etc) – “natural” human
cycle is about 25 hours
(mice = 23 hours)
•  Stretches 30-36 hours on
prolonged isola,on
•  Body has an intrinsic clock
that is constantly reset by
environmental clues
 Where is the
circadian clock?
•  A great deal is know at
the molecular level about
the circadian clock
mechanism
•  In mammals, the
circadian clock resides in
the suprachiasmaFc
nucleus (SCN)
•  Remove SCN, can’t
respond to light/dark
cycle, no circadian rhythm
(but not sleep itself!!)
 Input to SCN
•  Direct from re,na
•  For circadian rhythm,
light sensi,ve element is
not rod or cone.
•  Small number of ganglion
cells contain melanopsin
and project directly to
SCN
•  Melatonin à a hormone
that induces sleepiness
•  Internal clock resets every
morning
 AcFvaFon of Sleep

•  Entry/arousal from sleep can be fast

•  Sleep switch exists
•  Ventrolateral preopJc area represent that
switch
•  Sums circadian rhythm, sleep drive and
environmental cues
 Sleep

•  Sleep = a form of consciousness à lucid dreams

•  All higher vertebrates sleep
•  When asleep – temperature drops, respira,on
slows (save energy?)
•  Brain ac,vity changes
 EEG
•  Awake = mix of alpha (8-12 Hz) & beta (13-30 Hz)
waves
•  Sleep – 1st stage = theta (4-7 Hz) waves
•  Sleep – 2nd stage = K complexes & sleep
spindle
•  Sleep – 3rd / 4th stage = slow-wave sleep à
large & slow delta (1-3 Hz)
waves
 EEG and Sleep
•  Larger, more rhythmic brain waves are
characteris,c of sleep
•  Sleep is characterized by cycles of different
EEG paperns with corresponding changes in
brain behavior and responsiveness (REM vs
non-REM sleep)
 Non-REM sleep
“an idling brain in a moveable body”

•  Muscles relaxed, movement limited, BUT body

capable of movement
•  Temperature control lost, temperature drops,
metabolism down
•  Dreaming rare
•  Liple mental ac,vity
•  Difficult to awaken
•  Fours stages of EEG ac,vity (stage IV the
deepest)
 REM sleep
“an hallucina,ng brain in a paralyzed body”

•  EEG looks “awake”

•  Brain O2 consump,on higher than when you are
awake
•  Body is immobilized
•  Pronounced eye movements
•  Rela,vely easy to awaken
•  Temperature control lost, high but irregular heart
and respiratory rates
•  Clitoral and penile erec,on
•  Dreaming sleep
Sleep Cycle
Sleep cycle - example
REM sleep - Example
 Sleep Cycles
•  Cycle is roughly 90-100
minutes (REM sleep
25% of night)
•  REM more common late
in the night
•  Heart rate and
respira,on é in REM;
but ê in non-REM
REM sleep changes with age
 Sleep EEG in dolphins
•  Dolphins keep swimming, sleep one
hemisphere at a ,me
 Neural control of sleep

•  Sleep is an ac,ve process

•  Requires ac,va,on of specific groups of
neurons
•  Controlled by nuclei in brainstem and
hypothalamus
•  Waking state ac,vely maintained
 Brainstem and hypothalamic nuclei
•  Ascending re,cular system (cholinergic) – in
pons
•  Locus coeruleus (noradrenergic) – in midbrain
•  Raphe nuclei (serotonin) – in brainstem
•  Tuberomamillary nucleus (histamine) – in
hypothalamus

à All promote arousal and wakefulness
 Ascending Wakefulness Systems
•  Characterized by widespread inputs to
thalamus, cortex and spinal cord.

Purves et al., 2008 Fig.28.11

 ThalamocorFcal InteracFons
•  Thalamus innervates the
cortex
•  Thalamic neurons have two
stable states:
(1) directly reflects sensory
inputs
(2) thalamic neurons fire in
a coordinated slow
rhythm
•  State no.2 prevents sensory
inputs being passed to the
cortex
•  Brainstem ac,vity switches
rhythmic state OFF in
thalamic neurons
 Control of Arousal Centres
•  Two systems feed into the brainstem arousal centers
•  Orexins-releasing neurons in the tubomammilary nucleus
(TMN) s,mulate the arousal centres
•  The ventrolateral preop,c nucleus (VLPO) in hypothalamus
inhibits the arousal centres à promo,ng sleep
 Awake
•  During arousal (wakefulness) brainstem and
hypothalamic inputs excite cortex and allow thalamus
to pass sensory informa,on
 Non-REM sleep
•  During non-REM sleep:
- brainstem and hypothalamic inputs inhibited,
-  cortex entrained by thalamus,
-  no sensory input
 REM sleep
•  During REM-sleep, most brainstem and hypothalamic
inputs inhibited but ascending re,cular system s,ll
partly ac,ve and so cortex s,ll ac,ve with sensory
input
Sleep vs Arousal
 Motor paralysis in REM sleep
•  Motor neurons directly inhibited
•  Pon,ne centers also inhibit spinal cord (motor
inhibi,on)
•  Destroy pon,ne spinal inhibitory centers – cats
exhibit full motor programs during REM sleep
•  Ac,vity in locus coeruleus and raphe coincide
with wakefulness and alertness
•  Loss of these inputs leads to coma/
unconsciousness
 Summary of the cellular mechanisms that govern sleep
and wakefulness
Brainstem nuclei responsible Neurotransmi\er involved AcFvity state of the relevant
brainstem neurons

Wakefulness
-  Cholinergic nuclei of pons-midbrain Acetylcholine Ac,ve
junc,on
-  Locus coeruleus Norepinephrine Ac,ve
-  Raphe nuclei Serotonin Ac,ve
-  Tuberomammilary nuclei Orexin Ac,ve
Non-REM sleep
-  Cholinergic nuclei of pons-midbrain Acetylcholine Decreased
junc,on
-  Locus coeruleus Norepinephrine Decreased
-  Raphe nuclei Serotonin Decreased
REM sleep on
-  Cholinergic nuclei of pons-midbrain Acetylcholine Ac,ve (PGO waves)
junc,on
-  Raphe nuclei Serotonin inac,ve
REM sleep off
-  Locus coeruleus Norepinephrine Ac,ve
 What does sleep do?
•  Many theories
•  Strongest correla,on with memory
consolida,on of declara,ve memory (facts)
•  Memories are progressively strengthened to
ensure they are not lost. Sleep helps this.
 Memory consolidaFon
(Ellenbogen et al 2006, Current Biology 16:1290)
•  Used A-B, A-C memory recall
1.  Learn word pair A-B (i.e: leaf-wheel)
2.  Learn interfering word pair A-C (i.e: leaf-nail)
3.  Try and recall pair A-B


à More success if had sleep between 1 and 2
 Slow wave (NREM stage 3 and 4)
sleep seems important
(Gais et al 2007, PNAS 104: 18778)

•  Subjects learn word-pair list, tested aGer a

nights sleep
•  Some subjects had frontal lobes s,mulated
transcranially using direct current s,mula,on
during the night
•  Induced SWS-like (slow-wave-sleep) state and
enhanced recall
 Hippocampal memory is “replayed”
during sleep

•  Many studies claim hippocampal-cor,cal

networks that underlie learning are
reac,vated during SWS
•  Some studies have shown that the
improvement in next day recall correlates
with amount of hippocampal re-ac,va,on
 Inducing hippocampal recall
(Rausch et al 2007, Science 315:1426)

•  Smells can be strongly associated with memory

•  Subjects taught a spa,al memory task occupied
with smell of a rose
•  The subjects were exposed to the smell when
they were in SWS. This reac,vated the
hippocampus.
•  Exposure to smell during SWS sleep improved
recall next day, which was correlated with how
much ac,vity they had in sleeping hippocampus
 Sleep enhances insight?
(Wagner et al 2004, Biol.Psychiatry 60:788)

•  Subject learnt mathema,cal rules to carry out

a complex calcula,on
•  Sleep enhanced the speed of calcula,on
•  Sleep also enhanced the chance of discovering
a shortcut built into the calcula,on (60% vs
25%, sleep vs no sleep)
 Awareness & Arousal in Normal and
Impaired Consciousness
Brain & Behavior Fig.15.28

Lucid
dreaming Consciousness
Wakefulness
Awareness

REM drowsiness
sleep
Light sleep
Deep sleep
Minimally conscious state

General anesthesia
Vegeta,ve state
Coma

Arousal
 Sleep Disorders:
•  Insomnia à inalbility to sleep or obtain adequate-quality sleep, feels
inadequately rested.
•  Sleepwalking (somnambulism) à during slow-wave sleep. e.c gene,cs or
stress?
•  Narcolepsy à muta,on of orexin receptor
•  REM sleep behavior disorder
•  Delayed Sleep Phase Disorder (late bed,me and rising) à PER3 clock gene
involvement. Disorders of circadian rhythm à muta,on of circadian clock gene
CKIδ and PER2.
•  Restless legs syndrome
•  Obstruc,ve Sleep Apnea (OSA)
•  Sleep paralysis
•  Night terror (sleep terror disorder)
•  Somniphobia (anxiety & panic apacks before and during apempts to sleep)
Brain Areas involved in Memory &
Learning

Purves Neuroscience chapter 31

 Major categories of human memory

Immediate Memory Working Memory Long-term memory

(frac,ons of a second- (seconds-minutes) (days-years)
seconds)

Forgefng

Human vs Monkey
 DefiniFon
•  Learning = the process by which new
informa,on is acquired by the nervous system
and is observable through changes in
behavior.

•  Memory = the encoding, storage, and retrieval

of learned informa,on
 QualitaFve categories of Human
Memory

•  DeclaraNve Memory = the storage & retrieval of

material that is available to consciousness and
can in principle be expressed by language.
i.e: remember phone number, past even, the words to a song.

•  Non-declaraNve memory (procedural memory) =
not available to memory. Involve skills.
i.e: knowing how to use your phone, how to sing a song
 DeclaraFve Memories
•  Episodic memory (events)
•  SemanJc memory (facts)
•  Autobiographical memory (informa,on about
oneself)
•  SpaJal memory (the loca,on of the individual
and of objects in space)
Unconscious vs Conscious Memory
Non-declaraFve memory, involves :
•  Basal ganglia
•  Prefrontal cortex
•  Amygdala
•  Sensory associa,on cor,ces
•  Cerebellum

Not involves:
•  Medial temporal lobe
•  Midline diencephalone
Memory ConsolidaFon & Priming
•  Memory ConsolidaNon = the way in which
immediate and short-term (working) memories
are gradually encoded as long-term memories

•  Priming = a change in the processing of a

s,mulus due to a previous encounter with the
same or a related s,mulus with or without
conscious awareness of the original counter.

à memories, even those we feel quite confident
about, are o7en false.
Where are memory stored?

Hippocampus
 Sopir taxi di London-UK
•  Structural MRI showed enlarged posterior hippocampi di
London cabbies compared to non drivers
•  Could larger hippocampi lead to innately beper spa,al
skills?
à Hippocampal size correlated with experience
•  Evidence that changes in hippocampal grey maper are
acquired with experience
Tes,ng Memory in rodent
 Tes,ng Memory in mice

(Exist in NR2B à Faster

all NMDA in firing, quick
receptors) in plas,city but
decrease in
development
Tes,ng Memory in Mice
Measuring AcFvity of Neurons
Short-term Memory

Short-term Memory:

Inser,on of AMPA receptors,
phosphoryla,on, enhanced presynap,c
release via retrograde signaling (short-
term memory)
Long-term Memory

Long-term Memory:

Protein synthesis, structural changes
 AcquisiFon and storage of AcquisiFon and storage of
declaraFve informaFon non-declaraFve informaFon

Short-term memory storage Short-term memory storage

(hippocampus and related (sites unknown but
structures) presumably widespread)

Long-term storage Long-term memory storage

(a variety of cor,cal sites: (cerebellum, basal ganglia,
Wernicke’s area for the meaning
of words, temporal cortex for the premotor cortex, and other
memories of objects and faces, sites related to motor
etc.) behavior)
 Brain changes in Learning

•  Learning is a form of neural plas,city that

changes behavior by remodeling neural
connec,ons.

•  Specialized neural mechanism have evolved to

make most of this capability.

 Brain changes in Learning
•  Long-term potenFaFon (LTP) à an increase in
synap,c strength resul,ng from the simultaneous
ac,va,on of presynap,c neurons and post-synap,c
neurons.
i.e : process in working memories & learning

•  Long-term depression (LTD) à a decrease in the

strength of synapses that occurs when s,mula,on of
presynap,c neurons is insufficient to ac,vate the
postsynap,c neurons.
i.e : mechanism to modify memories & to clear old
memories to make room for new informaJon

Neurons & Memory FormaNon
Theories of learning & forgefng

 CondiFoned Learning
•  DefiniNon = the genera,on of a novel response
that is gradually elicited by repeatedly pairing a
novel s,mulus that normally elicits the response
being studied.
•  2 forms : classical & operant condi,oning

à Non-declara,ve memory
 1. Classical CondiFoning

•  An innate reflex is modified by associa,ng its

normal triggering s,mulus with an unrelated
s,mulus; by virtue of the repeated
associa,on, the unrelated s,mulus eventually
triggers the original response.
•  i.e : Ivan Pavlov’s experiment.
 2. Operant CondiFoning
•  The altered probability of a behavioral
response engendered by associa,ng the
response with a reward (or, punishment)
à posi,ve reinforcement
à nega,ve reinforcement
•  i.e : - Edward Thorndike’s experiment (law of
effect)
- Skinner box
Thorndike’s Law of Effect
Skinner Box
•  Both classical & operant condi,oning à takes
a number of trials for the condi,oning to
become established.

•  If the condi,oned animal performs the

desired response but the reward is no longer
provided, the condi,oning gradually
disappears à ExNncNon
 Forgefng
•  The human brain is very good at forgeung!!

•  We forget things that have no par,cular

importance, and unused or unrehearsed
memories deteriorate over ,me.

•  Our brain would be impossibly burdened with

the welter of useless informa,on that is
briefly encoded in our immediate and working
memory “register” or “buffers” à Forget.
 ReconsolidaFon
•  Each ,me a memory is retrieved, it must be reconsolidated,
and during that ,me the memory becomes even more
vulnerable.

•  Reopening a memory provides the opportunity to refine it,

correct errors, and modify your emo,onal response to
redheaded acquaintances.

•  Can be used to eliminate fear response in humans

(therapeu,c usefulness)

•  However, it also allows the introduc,on of new errors à

memory get “reconstructed” over ,me, usually by blending
with other memories.
Fletcher. NEUR30004_SMHF.
Can brain training make us smarter?

Playing acFon games (in

moderaFon) improves reacFon Fme
and focus.
(Bavalier et al., 2013)
Exercising the brain

-  Release of growth factors (i.e:

BDNF) and regeneraFon of new
neurons
-  Improvements in mood and
memory

-  Increased blood flow to brain

-  Elevated mood
-  Increased birth of new neurons?
-  Improves learning and memory?
 Amnesia

The Failure of storage and retrieval

 Amnesia
•  Forgeung is a normal & essen,al mental
process. But it can also be pathological à
Amnesia.

•  Anterograde amnesia = an inability to establish

new memories following neurological insult.

•  Retrograde amnesia = difficulty retrieving

memories established prior to the precipita,ng
neuropathology.
Unconscious vs Conscious Memory
The Legacy of H.M (Henry Molaison)
•  Bilateral resec,on of medial
structures of the temporal lobe, to
treat severe epilepsy (Scoville and
Milner, 1957)
•  Profound impairment of recent
memory in absence of other
intellectual loss (IQ = 112 post
surgery)
•  Could not remember what he had
for breakfast, find his way around
hospital or recognize anyone he
had met since the surgery.
H.M case – “severe anterograde amnesia
(+ retrograde amnesia)”
MRI reveals – medial temporal lobe lesion
 The legacy of H.M

He was able to hold H.M could recall

immediate impression memories from his
in his mind but as soon childhood
as his apen,on was
diverted, they were
lost.
 The Legacy of H.M

-  H.M demonstrated improvement, even though he was unable

to recall having previously done the task
-  Unconscious memory??
“Every day is alone”
“whatever enjoyment I’ve had and whatever
sorrow I’ve had”

- Henry Molaison (1926-2008) -
Clive Wearing – The man with no short term memory
Clive Wearing – anterograde amnesia
 Brain Areas Involved in EMOTION

Ref: Purves Neuroscience ch. 29, 30 & Garret’s Brain & Behavior ch. 5, 7 & 8
The Role of Feedback From The Body

Theory :
1.  James-Lange Theory of Emo,ons
2.  Cannon-Bard Theory of Emo,ons
 1. James-Lange Theory

Fight or
flight
2. Cannon-Bard Theory

Fight or
flight
James-Lange vs Cannon-Bard
James-Lange vs Cannon-Bard
 EmoFon Network
•  EmoFons originated in the Limbic System:
-  Prefrontal cortex (orbital and medial)
-  Basal ganglia (ventral por,ons)
-  Mediodorsal nucleus of the thalamus
-  Amygdala

•  Another important components:

-  Hippocampus Major roles in learning
-  Mammillary bodies
-  Anterior cingulate cortex EmoFon, a\enFon, conscious
emoFonal experiences
-  Hypothalamus
Limbic System
Prefrontal Cortex
•  Damage to the
prefrontal area à
impairs people’s ability
to make ra,onal
judgments.
•  Deficiencies in this area
à Unable to restraint
violent urges.
•  Abnormali,es in this
area à depression,
schizophrenia
 Prefrontal Cortex

•  The prefrontal cortex’s connec,ons to other

parts of the brain (amygdala, hippocampus,
etc) determine whether we are novelty-
seeking adventurer or are more restrained.

i.e: Do I want to skydiving (novelty-seeking

adventurer) OR stay at home (reward
dependent)?
 Amygdala

•  The prefrontal areas receive much of their

emo,onal input from the amygdala.
•  Amygdala à a small limbic system structure
in each temporal lobe that is involved in
emo,ons, especially nega,ve ones.
•  Amygdala à almond-shape structure deep
within the temporal lobe.
•  Mainly involved in Fear & Anxiety
 Amygdala subnuclei:
1.  Medial amygdala (MeA)
2.  Central amygdala (CeA)
à output of emo,onal
responses
3.  Basolateral amygdala
(BLA)
4.  Basomedial amygdala
(BMA)
5.  Lateral amygdala (LA)
•  Experiments on rhesus monkeys by Heinrich
Klüver and Paul Bucy à removed a large part of
both medial temporal lobes (destroying much of
the limbic system):
-  Visual agnosia
-  Hyperac,vity & hypersexuality Klüver-Bucy
-  Virtually tame Syndrome

-  Show no fear (!!!)

Klüver-Bucy syndrome à could be elicited by
removal of the amygdala alone.
•  Dangerous situa,ons à induce fear à learn how to avoid (role of
hippocampus & amygdala) à survival
•  Learning Process à classical condiJoning à Ivan Pavlov’s
experiment.
Hemispheric SpecializaFon in EmoFon
•  Both hemispheres are involved

•  LeG frontal area à posi,ve emo,ons

•  Right frontal area à nega,ve emo,on

•  Damage to leG hemisphere à more anxiety and

sadness. The incidence and severity of depression is
significantly higher in paJents with lesions of the leE
anterior hemisphere.
•  Damage to right hemisphere à unperturbed,
euphoric. PaJents with lesions of the right anterior
hemisphere are oEen described as unduly cheerful.
 Hemispheric SpecializaFon in
EmoFon

•  Right Hemisphere à more specialized for its

expression (i.e: facial expressions and
emo,onal scenes)

•  Damage to right hemisphere à trouble

recognizing emo,on from the tone of the
speaker’s voice and their own speech is
usually emo,onless.
 Stress, Immunity & Health
•  Stress is adap,ve, mobilizing the body for ac,on and
increasing immune system ac,vity
•  Prolonged stress à interfere with mental, physical and
emo,onal func,oning; compromising the immune
system, damages the brain (extreme stress) and even
produce death.
•  Stress can cause sudden death à e.c excessive
sympathe,c ac,vity leads to heart fibrilla,on à heart
apack.
•  PTSD pa,ents à reduced hippocampal volume (caused
by cor,sol é) à short-term memory deficits & slight
intelectual impairment.
•  PTSD pa,ents are suggested to have increased
sensi,vity to cor,sol.
 Pain as an AdapFve EmoFon
•  Pain is necessary as a warning sign to our body.
•  Congenital insensiJvity to pain à unable to sense
pain.
•  Pain is one of the senses à in,mately involved
with emo,on. Emo,onal response makes pain
adap,ve.
•  Pain pathway has rich interconnec,ons with the
limbic system.
•  Pain ac,vates the anterior cingulate cortex which
is in,mately connected with other limbic
structures.
•  Example : case of wounded soldiers in world war II.
 Aggression
•  Aggression = behavior that is intended to harm.

•  Two types:
1. Predatory aggression
à when animal apacks and kills its prey, or when a human
makes a premeditated, unprovoked apack on another.
à  Cold & emo,onless (sympathe,c ac,vity is not
involved)

2.  AffecFve aggression

à  Characterized by its impulsiveness and emo,onal
arousal.
à  Offensive (apack to guard territory) and defensive
(apack to defense/b.c of fear) affec,ve aggression
 Hormones & Aggression
•  Aggression is influenced by environment à Has hormonal &
neural roots.
•  In non-primate animals à aggression is enhanced by
testosterone in males & both testosterone + estrogens in
females.

•  In Primates & humans:

−  Aggressiveness éé à pre-menstrual period in females
monkeys à e.c low progesterone & estrogen.
−  Violence in male & female inmates à e.c Testosteron éé
−  Aggression increases testosterone level
 The Brain’s Role in Aggression
•  Defensive pathways : •  Predatory a\ack :
medial nucleus of the Lateral and central
amygdala (MeA) nucleus of the
ê amygdala (LA and CeA)
medial hypothalamus ê
ê lateral hypothalamus
dorsal part of the ê
periaqueductal gray ventral PAG
(PAG) in the brainstem.

•  A predisposing factor for human aggression à deficiency
in Prefrontal func,oning.
•  Men have less gray maper in the prefrontal cortex than
women à thus, 77% greater an,-social behavior.
•  Reduced volume of gray maper in the prefrontal cortex à
characteris,c of an,-social personality.

•  AnNsocial personality disorder à behave recklessly,

violate social norms, commit an,social acts (i.e: figh,ng,
stealing, using drugs, sexual promiscuity)

•  NOTE: deficiency in prefrontal func,oning alone IS NOT

ENOUGH to produce violence! à the prefrontal areas
ordinarily inhibits urges, but those urges originate in
subcor,cal areas (i.e amygdala).
According to studies:
•  Lession of the amygdala à reduced aggressive
behaviors in 33-100% of pa,ents with severe
aggressive disorders.
•  Male & female murderers à higher ac,vity in right
subcor,cal areas, including the amygdala,
hippocampus, thalamus & midbrain (PET scan).
•  Affec,ve murderers à lower prefrontal ac,vity;
predatory murderers à normal prefrontal ac,vity
•  Psycopath (lack of empathy & remorse) à 22%
reduc,on in prefrontal gray maper

à The PFC deters aggression and an,-social behavior
BUT in others with stronger urges, PFC func,oning
determines whether the aggression will be uncontrolled
or planned and directed.
 Emo,ons & Neurotransmiper
•  3 neurotransmiper involved in aggression behavior: Dopamine,
GABA & Serotonin.
•  Dopamine à contributes to arousal
•  Low GABA ac,vity à impulsivity
•  Low serotonin à increases dopamine
•  Decreased serotonin ac,vity in PFC à impulsive aggression
•  Low serotonin + high testosterone level à aggression éé
•  Alcohol consump,on + low serotonin level à aggression in humans
•  Alcohol ini,ally increases serotonin ac,vity then depletes it below
original level à increase craving for more alcohol
•  Alcohol consump,on increases both aggression and the desire for
more alcohol in alcohol abusers.

•  Drugs (such as An,depressant Fluoxe,ne) inhibit serotonin uptake

at the synapse à reduce alcohol craving and intake + reduce
hos,lity and aggressiveness.
 EmoFonal Reinforcement and
AddicFon
•  The limbic system can signal the presence of or
prospect for REWARD AND PUNISHMENT, as well as
promo,ng the ac,va,on of motor programs aimed
at procuring beneficial rewards and avoiding
punishment.

•  Heroin, cocaine, alcohol, opiates, marijuana,

nico,ne, amphetamines and their synthe,c analogs
à act on elements of the limbic circuitry à altering
the neuromodulatory influence of dopamine in the
ventral divisions of the basal ganglia à
consolida,on of addic,ve behavior in limbic
circuitry.
Nucleus Accumbens and
Ventral Tegmental Area
(VTA) à primary sites à
related to drugs abuse
and emoFonal
reinforcement
 Brain’s Reward System

The MesolimbocorFcal dopamine system à role in drug addic,on,

feeding, sex and other behaviors
Brain’s Extended Reward System
 Drugs abuse affect dopamine projecJon
(VTA & N.Acc) à hijack the brain reward system
 AddicJon Hijacks the Brain
•  A study found that when cocaine addicts were
shown pictures of drugs for just 33 mseconds (less
,me than it takes for the images to enter addicts’
consciousness) à their drug craving returned.

•  Drugs also disrupt brain circuits involved in impulse
control in the prefrontal cortex à reason on why
adolescents are more suscep,ble to addic,on (the
PFC does not fully developed un,l mid 20s).
 Love is a Drug?
•  Brain system “being in love” à reward & reinforcement.
•  Roman,c love à ac,vity of 2 pep,de hormone neurotransmiper:
Oxytocin & Vasopressin.

•  Person in love à brain regions normally regulate social interac,ons (i.e
cerebral cortex & basal forebrain, including amygdala) are diminished
in ac,on. Studies using fMRI à maximal ac,vity in the caudate
putamen & VTA.
•  Person recently rejected by love interest à maximal ac,va,on in the
VTA & caudate nucleus; in addi,on also ac,vate à cor,cal regions
associated with mo,va,on, calcula,on of gain and loss (such as
gambling or risk taking), emo,onal regula,on, and drug craving!

•  Animal studies (prairie voles)à dopamine & vasopression influence

monogamous mate selec,on. Injec,on of vasopressin antagonist into
ventral pallidum of male prairie voles or dopamine antagonists into
N.Acc of female prairie voles à monogamy is disrupted.
 Love – Sexuality
•  Sex involves arousal & sa,a,on à a form of mo,va,on (a need of the
brain)
•  The key elements in human sexual behavior: Testosterone, Structure in
Hypothalamus, and sensory s,muli such as certain physical
characterisJcs & pheromones.

•  3 Factors to determine sexual preferences (Hetero~ & Homo~):

GeneNc, (pre-natal) hormonal and Neural.
à X-chromosome: increases aprac,on to men (in both men & women)
à  Parents with ‘a bit off’ testosterone levels
à  Third inter,,al nucleus of the anterior hypothalamus (INAH3) à ½
size in HomoM (similar size with HeteroW) than HeteroM;
Suprachiasma,c nucleus (SCN) was larger in HomoM
à  In HomoM à androgens ac,vate the anterior hypothalamus (similar
to HeteroW)
à  In HomoW à estrogens ac,vate the anterior hypothalamus (similar
to HeteroW)
Selamat Belajar!