Transcript Lecture 18

Disorders of Memory
Amnesia & Animal Models
Lecture Outline
Disorders of Memory
•H.M.
•Anterograde Amnesia
•Retrograde Amnesia
•Korsakoff’s Syndrome
Animal Models of Memory
Anatomy of Memory
Prefrontal lobes
• important for short-term memory.
Temporal lobes
• hippocampus and amygdala.
• processing of short-term to long-term memory.
Diencephalon
• thalamus, hypothalamus, mammillary bodies.
• processing of short-term to long-term memory.
Disorders of Memory
• Retrograde – loss of memory for events prior to injury.
• Anterograde – inability to form new memories.
• Post-traumatic Amnesia (PTA) – period of time after brain injury
during which new memories can not be formed (patient is also usually
disoriented in time and space).
Who is H.M.?
coronal MR slices
• Patient H.M. suffered from
epilepsy thought to be caused
by a head injury at age 9.
• H.M.’s epilepsy could not be
controlled through drug
interventions.
• H.M. underwent bilateral
temporal lobotomies in 1958.
H.M.
Healthy control
The medial temporal lobes (MTL)
Who is H.M.?
• Surgery successfully treated epileptic seizures, but left severe memory
impairments.
• His memory for the remote past was intact (could remember his
childhood), but he had some retrograde amnesia and severe
anterograde amnesia.
• If you left H.M. for only a few minutes, upon returning he would
most likely forget who you were or that you had already met!
• Loss of episodic memory. Semantic memory generally intact.
• Semantic – memory for factual based material.
• Episodic – memory for events that can be linked to a time and place.
What is it like to be H.M.?
• “Right now, I’m wondering, ‘Have I done or said anything amiss?’
You see, at this moment everything looks clear to me, but what
happened just before? That’s what worries me. It’s like waking
from a dream.”
-- H.M., 1965
• “Every day is alone in itself, whatever enjoyment I’ve had, and
whatever sorrow I’ve had.”
-- H.M., 1968
What Is Memory?
Classic cases of amnesia
The case of N.A.
• A small lesion in the left dorsomedial nucleus of the thalamus.
• Similar pattern of deficits to H.M.
• Retrograde amnesia for the 2 years preceding the accident.
• Almost complete anterograde amnesia – can remember
virtually nothing of events since the accident.
• More verbal than visual memory deficits, although both
domains affected (e.g., has spatial memory impairments).
• Episodic lost but semantic intact.
What Is Memory?
Classic cases of amnesia
What types of functions may be left intact in cases of severe amnesia, such as H.M.,
Clive and N.A.?
• immediate memory – can recite back several words immediately (but within
five minutes no recollection of words).
• intact memory for remote events (e.g., from childhood).
• factual knowledge (e.g. water boils at 100°C).
• perceptual and motor memory (e.g. riding a bike, brushing teeth).
• language and social skills.
• procedural learning (e.g. mirror drawing).
• Other facets of functioning:
• Personality
• Intellectual Functioning
Insight into intact and impaired functions in amnesics enables us to learn much about
memory processing.
H.M. – procedural learning.
• Task – draw object viewed in the
mirror.
• Practice makes perfect – even in
H.M.
• Never recalls having done the test!
• Implicit memory.
• stem-completion also intact – e.g.,
DEFEND, HELIUM, MODIFY
DEF__________
DEFEND, DEFEAT, DEFINE
H.M.’s Contribution to Memory Research
The hippocampus is NOT the location of LTM, and is NOT necessary
formation of LTM.
• can remember childhood.
The hippocampus is NOT the location of STM.
• can carry on conversations.
The hippocampus IS responsible for converting STM into LTM.
• understands new information, but a permanent record is never
made.
• involved in consolidating memories overtime.
Hypothesized Memory Processes
Performance
Retrieval
Incoming
information
Working
memory
Sight
Sound
Smell
Touch
Sensory Encoding
buffers
Attention
Short-term
storage
Long-term
storage
Consolidation
Rehearsal
Anterograde Amnesia
What brain regions are critical in anterograde amnesia?
• for H.M. the hippocampus and parahippocampal cortex were
removed (as was the amygdala).
Parahippocampal cortex: A region of limbic cortex adjacent to the
hippocampal formation that, along with the perirhinal cortex, relays
information between the entorhinal cortex and other regions of the
brain.
• amygdala is probably only important for the emotional content of
memories – flashbulb memories.
• amnesic patients can perform memory tasks, but they cannot learn
anything they learned from it.
Double Dissociation
Proof the hippocampus mediates consolidation?
Patient S.M. - bilateral amygdala damage.
• could not establish conditioned emotional responses.
Patient W.C. - bilateral hippocampal damage.
• could not remember testing procedure.
• episodic (declarative) memory impaired.
Patient R.H. - bilateral damage to both.
• both kinds of learning impaired.
Korsakoff’s amnesia
• severe anterograde amnesia.
• destruction of parts of diencephalon (mammilo-thalamic tract).
• temporally graded retrograde amnesia.
• lose declarative memories but not procedural ones.
• confabulation is common.
• caused by thiamine deficiency due to alcoholism and poor diet.
Retrograde amnesia and the temporal gradient
% correct
MTL amnesics
Korsakoff’s patients
1990
1980
1970
1960
1950
1940
Korsakoff’s patients show a steep temporal gradient in their
remote memories
Retrograde amnesia and consolidation
• temporal gradient to retrograde amnesia.
• for closed head injury or even ECT (shock therapy) – memory loss is
greatest for most recent events and rarely extends beyond a few years.
• retrograde amnesia is quite severe in Wernicke-Korsakoff’s syndrome
but still maintains a temporal gradient – suggests hippocampus is not
the only structure necessary for memory.
Confabulation
• more than just “filling-in-the-blanks”.
• patients with Wernicke-Korsakoff’s will make up information to hide
a memory deficit.
• indicative of a lack of awareness of the memory impairment (frontal
lobe involvements).
The story so far…
• Memory involves multiple brain regions
• medial temporal lobes
• hippocampus
• entorhinal cortex
• parahippocampal cortex
• amygdala
• subcortical structures
• mammilo-thalamic tract
• neocortex
• posterior superior temporal gyrus
• dorsolateral prefrontal cortex
Animal Models of Memory Research
• We have learned a lot about memory from case studies, but individual
cases are not as statistically powerful as group studies.
• We know that different brain structures have different roles in learning
and memory.
• Human memory research provides research direction, but animal
research is needed for in depth analysis.
Animal models of memory
Delayed match to sample
Delayed non-match to sample
Spatial memory – animal models
• hippocampal lesions disrupt learning in a radial arm maze or Morris
water maze.
Now have Virtual Reality Morris water mazes for humans
Prefrontal cortex
• output from BG – thalamus,
from there to prefrontal and
SMA
• premotor, SMA involved in
planning & execution
• important for learning
sequences of movements
Triple Dissociation
• MacDonald & White used the radial arm maze (RAM) to examine
declarative, procedural and emotional memory.
• Evidence for different memory systems mediated by different brain
structures.
• Lesions to the hippocampus produced deficits in declarative memory.
• Lesions to the basal ganglia produced deficits in procedural memory.
• Lesions to the amygdala produced deficits in emotional memory.
Review Questions
1) People with anterograde amnesia
A) are unable to recall childhood experiences.
B) show impairments in motor memory.
C) show normal complex relational learning.
D) are unable to learn new information.
E) show facilitated stimulus-response learning.
2) The most profound symptom of Korsakoff's syndrome is
A) anterograde amnesia.
B) total amnesia.
C) combative behavior
D) delirium tremens.
E) auditory and visual hallucinations.
3 ) Which of the following is true of confabulation?
A) Confabulation is seen in persons who simply mix up their memories.
B) Confabulation is intentional.
C) Patient H.M. shows severe confabulation.
D) Korsakoff's patients fail to show confabulation.
E) Confabulation is the report of a fictitious event by a person with amnesia.
Review Questions
4) One striking aspect of H.M.'s memory deficit is that he
A) can learn some new tasks, but is unaware of having learned them.
B) only remembers recent facts.
C) reverses word order in repeated sentences.
D) indicates he remembers things he has never seen.
E) show signs of confabulation.
5) Which of the following is true of short-term memory?
A) Immediate memory precedes short-term memory.
B) Short-term memory has a limited capacity.
C) Short-term memory is impaired by repetition of verbal material.
D) Short-term memory has an unlimited capacity.
E) Immediate memory is distinct from short-term memory.
6) When tested in an 8-arm maze, a rat with hippocampal damage will
A) repeatedly visit arms from which they have already eaten a food pellet.
B) be unable to visit all of the arms.
C) be more efficient at getting food than is an intact rat.
D) only visit arms that have never held food in the past.
E) perform more efficiently than will a rat with damage to the fornix or entorhinal cortex.