Disorders of MemoryAmnesia & 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.

• processing of short-term to long-term memory.

Diencephalon • thalamus, hypothalamus, mammillary bodies.

Temporal lobes • hippocampus and amygdala.

• 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.?

• 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.

coronal MR slices

H.M. Healthy control

The medial temporal lobes (MTL)

• 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.

Who is H.M.?

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

Incoming informati

on

Performance

Retrieval

Working memory

Short-term storageEncodin

g

Long-term

storage

Consolidation

Sensory

buffers

Sight

Sound

Smell

TouchAttenti

onRehear

sal

Anterograde AmnesiaWhat 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

Korsakoff’s patients show a steep temporal gradient in their remote memories

1990 1980 1970 1960 1950 1940

Korsakoff’s patients

MTL amnesics%

corr

ect

• 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.

Retrograde amnesia and consolidation

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.

1) People with anterograde amnesiaA) 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 isA) anterograde amnesia.B) total amnesia.C) combative behaviorD) 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 heA) 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 willA) 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.

Review Questions