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Prof. Stephan Anagnostaras
Lecture 3: HM, the medialtemporal lobe, and amnesia
Neurobiology ofLearning and Memory
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Serial model
Memory terminology based on information processing models
e.g., Serial Model
Can test these models in brain damaged subjects
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Amnesia
Amnesia Partial or total loss of memory, usually resulting from
shock, psychological disturbance, brain injury, or illness.
Organic caused by shock, brain injury, illness• hypoxic episode,
herpes encephalitis• epilepsy, brain injury, Alzheimer’s
disease
Psychogenic caused by psychological trauma• dissociative
disorders• psychogenic fugue• multiple personality disorder
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Amnesia
Amnesia can be global or material-specific
Global any kind of information is affectedMaterial-specific
certain kinds of material
(e.g., faces)
Amnesia can be anterograde or retrograde
Anterograde amnesia inability to learn anything newsince the
time of the trauma (usually organic)
Retrograde amnesia loss of memory for events priorto the time of
the trauma (psychogenic or organic)
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HM
Most famous case reported by Scoville& Milner (1957)
Scoville did the surgeries for psychosisbut didn’t work, so
tried it for epilepsy onabout 30 patients. Patients studied
byBrenda Milner
HM: bilateral medial temporal lobelesion for status epilepticus
in 1953
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HM’s lesion: bilateral medial temporal lobe removal
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HM = no hippocampus, amygdala, overlying (rhinal) cortex
normalhpc
HM = no hpc, no rhinal ctx
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HM = no hippocampus, amygdala, overlying (rhinal) cortex
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HM’s amnesic syndrome
Severe deficit (global anterograde amnesia)• show word or face,
ask later, doesn’t know• reads newspapers repeatedly• doesn’t
remember own physician• see on formal tests or everyday life
• word lists• faces and objects• recall or recognition
Only mild retrograde amnesia• loss of memories that are a up to
2-3 years old at thetime of the lesion, but childhood memories in
tact• known as a time-limited or
temporally-graded retrograde amnesia
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Retrograde vs. anterograde amnesia
for HM, retrograde amnesia is approx. 2 yrs
normal memoryfor remote events(childhood, etc)
HM also has this
Retrograde and anterogradeamnesia can occur togetheror
separately (HM has both)
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Remote versus Recent Memory:HM, Loss of Recent memory
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Medial temporal lobe amnesia:what’s special?
Deficit very specific for Long-Term Memory (LTM)• not dementia•
IQ normal and unchanged• perceptual skills excellent• social skills
and personality intact• Short-Term Memory (STM = 3 min, 7±2 items)
good (e.g., digit span)• forgetting curve for STM normal• Memory
scale more than 3 std dev from controls!
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Rey-Osterrieth Figure
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Rey-Osterrieth Figure
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Famous Faces test of explicit memory and retrogradeamnesiaNF =
non-famous (control)
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Retrograde amnesia often shows a gradient: memory forolder
events (1950’s) is better than memory for newerevents (1980’s)
Amnesics worse than controls
Damage to hpc = Memory that was still in hpc “buffer”got lost
before it could be consolidated into permanent memoryelsewhere in
the brain
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Spared learning
Learns some things normally:• visual motor pursuit• priming•
mirror drawing task• normal eyeblink classical conditioning
(e.g., puff of air/tone on eye but not fear)• but doesn’t ever
remember doing task before (source
amnesia)These tasks do not necessarily share anything
incommon.
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HM could improve on task but didn’t recognize task eachday
Fig. 14.4
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HM improved in performance despite not remembering thetest
Fig. 14.6
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Repetition Priming: Testing ImplicitMemory (Graf et al.,
1984)
ABSENT ABS__________INCOME INC__________FILLY
FIL__________DISCUSS DIS__________CHEESE CHE__________ELEMENT
ELE__________
First the list: Then complete the word: Amnesics don’t remember
word list well
But they still can complete the fragment
with the previously seen word
• free recall• cued recall: complete word stem with specific
word from study list
abs____ ??• word stem completion: complete word stem with first
word that comes to mind
dis___??• same cue in cued recall & word-stem completion but
only cued recall requires conscious access to past
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Mirror Reading
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Some spatialmemory
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Explicit versus Implicit Memory
Memory impacted by the lesion termed explicit (ordeclarative)
memory - must be stated verbally andrequires conscious recollection
(note: doesn’t work foranimals) -includes semantic (facts,
knowledge) andepisodic (events, memory) memory
Not disrupted: implicit memory (procedural ornondeclarative) -
learning is demonstrated throughperformance and may not be
available to verbalrecollection (e.g., tying your shoelaces)
Note that implicit memory is a junk term thatincludes several
different forms of memory,including most forms of classical
conditioning
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Neuroanatomy
• The hippocampus is the critical structure for explicit
memoryPatient RB: damage only to CA1
• Disruption of hippocampal-circuitry can give a similar deficit
(dorsomedial thamalus)
• The greater the disruption to surrounding cortex the more
severe the amnesia
• Anterograde and retrograde amnesia usually correlated (HM is
an exception)
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More selective brain damage can produce explicit memoryproblems
(amnesia), also
Korsakoff’s amnesia:damage to MD thalamus
(diencephalon area of brain)
Pt R.B.:damage to CA1 area of hpc (very selective)
medial diencephalicamnesia
(Korsakoff’s and Pt N.A.)Zola-Morgan, Squire, & Amaral,
1986
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RB’s brain
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Herpes encephalitisNormal
Herpes SimplexEncephalitis
Reed & Squire (1998)
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Alzheimer’s disease: plaques & tangles in memory areas
•severe and more general memory loss (explicit + verbal
implicit, e.g., priming)
•affects entorhinal ctx (1), then hpc (2), frontal (3), parietal
(3) lobes
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Other forms of amnesia
Unilateral hippocampal damage resultsin material-specific
deficits
left = words, names, etc.right = faces, objects, etc.
Korsakoff’s psychosis results in similaramnesia plus
confabulation
Frontal lobes STM, working memory,temporal order,
confabulation
Electroconvulsive Therapy (ECT,ECS)
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Multiple memory systems in the brain
Explicit memoryImplicit memory
Facts(semantic)
Events(episodic)
Medial temporal lobe; diencephalon
Procedural memory:skills & habits(basal ganglia) Skeletal
musculature
(cerebellum)
Classical conditioning
EmotionalResponses(amygdala)
Priming(neocortex)
Eyeblink conditioning inrabbit
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HM normal on this? Explicit or Implicit learning?
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Classical (Pavlovian) conditioning and memory
There are many different forms of classical conditioningand the
responsible brain structure depends on the form
Examples: a) Pavlovian fear conditioning:
Tone --> Shock Then: Tone --> freeze(CS) (US) (CS)
(CR)
• Depends on the amygdala • + the hippocampus with trace
procedure• + the hippocampus if the CS is a context
b) Eyeblink conditioningTone --> puff of air to eye Then:
Tone --> eyeblink(CS) (US) (CS) (CR)
•Depends on cerebellum• + hippocampus with trace procedure
• Declarative knowledge of task always depends on
hippocampus