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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