Download NeuroAnatomic and Genetic Approaches to Memory Formation

Neurobiology of
Learning and Memory
Prof. Stephan Anagnostaras
Lecture 3: HM, the medial
temporal lobe, and amnesia
Serial model
Memory terminology based on information
processing models
e.g., Serial Model
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Can test these models in brain damaged subjects
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
Amnesia
Amnesia can be global or material-specific
Global any kind of information is affected
Material-specific certain kinds of material
(e.g., faces)
Amnesia can be anterograde or retrograde
Anterograde amnesia inability to learn anything new
since the time of the trauma (usually organic)
Retrograde amnesia loss of memory for events prior
to the time of the trauma (psychogenic or organic)
HM
Most famous case reported by Scoville
& Milner (1957)
Scoville did the surgeries for psychosis
but didn’t work, so tried it for epilepsy on
about 30 patients. Patients studied by
Brenda Milner
HM: bilateral medial temporal lobe
lesion for status epilepticus in 1953
HM’s lesion: bilateral medial temporal lobe removal
HM = no hippocampus, amygdala, overlying (rhinal) cortex
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normal
hpc
HM = no hpc, no rhinal ctx
HM = no hippocampus, amygdala, overlying (rhinal) cortex
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 the
time of the lesion, but childhood memories in tact
• known as a time-limited or
temporally-graded retrograde amnesia
Retrograde vs. anterograde amnesia
normal memory
for remote events
(childhood, etc)
for HM, retrograde amnesia
is approx. 2 yrs
Retrograde and anterograde
amnesia can occur together
or separately (HM has both)
HM also has this
Remote versus Recent Memory:
HM, Loss of Recent memory
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!
Rey-Osterrieth Figure
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Rey-Osterrieth Figure
Famous Faces test of explicit memory and retrograde
amnesia
NF = non-famous (control)
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Retrograde amnesia often shows a gradient: memory for
older events (1950’s) is better than memory for newer
events (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 memory
elsewhere in the brain
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 in
common.
HM could improve on task but didn’t recognize task each
day
Fig.
14.4
HM improved in performance despite not remembering the
test
Fig.
14.6
Repetition Priming: Testing Implicit
Memory (Graf et al., 1984)
But they still can
First the list:
ABSENT
INCOME
FILLY
DISCUSS
CHEESE
ELEMENT
Then complete the word:
ABS__________
INC__________
FIL__________
DIS__________
CHE__________
ELE__________
• 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
complete the fragment
Amnesics don’t
with the previously
remember word list well
seen word
Mirror Reading
Some spatial
memory
Explicit versus Implicit Memory
Memory impacted by the lesion termed explicit (or
declarative) memory - must be stated verbally and
requires conscious recollection (note: doesn’t work for
animals) -includes semantic (facts, knowledge) and
episodic (events, memory) memory
Not disrupted: implicit memory (procedural or
nondeclarative) - learning is demonstrated through
performance and may not be available to verbal
recollection (e.g., tying your shoelaces)
Note that implicit memory is a junk term that
includes several different forms of memory,
including most forms of classical conditioning
Neuroanatomy
• The hippocampus is the critical
structure for explicit memory
Patient 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)
More selective brain damage can produce explicit memory
problems (amnesia), also
Korsakoff’s amnesia:
damage to MD thalamus
(diencephalon area of brain)
Pt R.B.:
damage to
CA1 area of hpc
(very selective)
Zola-Morgan, Squire, & Amaral, 1986
medial diencephalic
amnesia
(Korsakoff’s and Pt N.A.)
RB’s brain
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Herpes encephalitis
Normal
Herpes Simplex
Encephalitis
Reed & Squire (1998)
Alzheimer’s disease: plaques & tangles in memory areas
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•severe and more general memory loss
(explicit + verbal implicit, e.g., priming)
•affects entorhinal ctx (1), then hpc (2), frontal (3),
parietal (3) lobes
Other forms of amnesia
Unilateral hippocampal damage results
in material-specific deficits
left = words, names, etc.
right = faces, objects, etc.
Korsakoff’s psychosis results in similar
amnesia plus confabulation
Frontal lobes STM, working memory,
temporal order, confabulation
Electroconvulsive Therapy (ECT,ECS)
Multiple memory systems in the brain
Explicit memory
Medial temporal lobe; diencephalon
Implicit memory
Classical conditioning
Facts
(semantic)
Events
(episodic)
Procedural memory:
skills & habits
Skeletal musculature
(basal ganglia)
(cerebellum)
Eyeblink conditioning in
rabbit
Priming
(neocortex)
Emotional Responses
(amygdala)
HM normal on this? Explicit or Implicit learning?
Classical (Pavlovian) conditioning and memory
There are many different forms of classical conditioning
and 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 conditioning
Tone --> 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