Human Brain Disorders and Memory Nicola J. Broadbent Ph.D Dept. Psychiatry UCSD School of Medicine

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Human Brain Disorders and MemoryNicola J.
Broadbent Ph.DDept. PsychiatryUCSD School of
Medicine
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Case H.M.

• Severely incapacitated by seizures despite
  maximum dosages of anticonvulsant medications
• At age 27, underwent experimental surgery that
  bilaterally removed the uncus, amygdala, parts of
  the hippocampus, perirhinal and parahippocampal
  cortices

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H.Ms Lesion
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Characteristics of Medial Temporal Lobe Amnesia

• Intact cognitive and intellectual abilites
• Normal I.Q.
• No change in personality, social graces intact
• Normal reasoning, abstract thinking and problem
  solving
• Spared immediate and working memory
• i.e. normal digit span

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Characteristics of Medial Temporal Lobe Amnesia

• Intact cognitive and intellectual abilites
• Spared immediate and working memory
• Anterograde Amnesia
• a persistant inability to remember new
  information and events which occur after the
  onset of amnesia.

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Declarative Memory

• Semantic memory
• memory for facts, world knowledge
• Episodic memory
• memory for an event that is autobiographical,
  and occurs in a specific time and place/context.

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Everyday is alone in itself, whatever enjoyment
Ive had, and whatever sorrow Ive had. Right
now, Im wondering. Have I done or said anything
amiss? You see, at this moment everything looks
clear to me, but what happened just before?
Thats what worries me. Its like waking from a
dream, I just dont remember (p. 217
Milner et al., 1968)
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Characteristics of Medial Temporal Lobe Amnesia

• Intact cognitive and intellectual abilites
• Spared immediate and working memory
• Anterograde amnesia
• Retrograde amnesia for premorbid events
• information acquired just prior to the brain
  damage is abolished, but information acquired at
  remote time points is spared.

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Characteristics of Medial Temporal Lobe Amnesia

• Intact cognitive and intellectual abilites
• Spared Immediate and working memory
• Anterograde amnesia
• Retrograde amnesia for premorbid events
• Spared Implicit Memory

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Damage to the medial temporal lobe does not
impair mirror drawing (nondeclarative/implicit
learning)
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Why is H.M.s case so important?

• Provided first strong evidence for the role of
  the medial temporal lobe structures in long-term
  memory (LTM)
• Showed that memory was dissociable from other
  cognitive abilities
• Amnesia with intact performance on implicit
  memory tasks suggests that there are multiple
  memory systems in the brain
• Working memory vs. LTM
• implicit memory vs. episodic and semantic memory

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LONG-TERM MEMORY
DECLARATIVE (EXPLICIT)
SEMANTIC (facts)
EPISODIC (events)
Hippocampus/ Medial Temporal Lobe
Squire 1992
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Declarative Memory vs. Nondeclarative memory

• Declarative Memory
• Facts and events
• Flexible use of information
• Acquired knowledge is available to conscious
  recollection or awareness
• Supported by the medial temporal lobe (and
  diencephalic structures)

• Nondeclarative memory
• Collection of memory abilities that support skill
  and habit learning
• Expressed through performance rather than
  recollection
• Unaware
• inflexible
• Supported by a wide array of brain regions
  specific to each type of memory

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Neural Substrate of Declarative Memory
MTL
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Case R.B.

• Became amnesic after complications following
  heart surgery (atrial tear and respiratory
  arrest).
• Extensive neuropsychological testing and
  postmortem neuropathological analysis
• First case to show that damage limited to the
  hippocampus (specifically the CA1) resulted in
  anterograde amnesia.

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Rey-Osterrieth Complex Figure
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Damage to the Hippocampus Impairs Recall of
Rey-Osterrieth Complex Figure
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Subjects with medial temporal lobe damage are
severely impaired at recalling the Rey-O figure.
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• Case RB demonstrates that damage restricted to
  the hippocampus is sufficient to result in
  anterograde amnesia
• RBs amnesia is milder than HM, suggesting that
  other medial temporal lobe regions also make
  significant contributions to memory.

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Case N.A.

• Became amnesic following a penetrating brain
  injury with a miniature fencing foil (up the
  nose!)
• MRI showed that damage was to the thalamic
  nuclei, mamillothalamic tract and mammillary
  bodies
• Dense anterograde amnesia
• Little retrograde amnesia
• Confabulation, disorientation in space and time

This case shows that in addition to the MTL, the
diencephalon is also involved in the formation of
declarative memories.
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What can cases with MTL or hippocampal damage
tell us about the characteristics of Declarative
Memory?

• MTL damage results in impaired Recall and
  Recognition memory
• Recognition memory the ability to identify a
  previously encountered item as familiar
• MTL damage impairs recognition memory across a
  wide array of modalities (odor, vision, audition)

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VISUAL PAIRED COMPARISON
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Declarative Memory Retrograde Amnesia

• CASE E.P
• Developed amnesia after contracting viral
  encephalitis
• MTL severely damaged
• Severe anterograde amnesia
• Temporally limited retrograde amnesia

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Like H.M, E.P has normal IQ, perception and other
cognitive abilities
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E.Ps working memory is normal
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E.P has severe Anterograde Amnesia
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E.P has severe Anterograde Amnesia
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Teng and Squire (1999)
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EP can navigate around his childhood neighborhood
demonstrating intact remote spatial memory
Teng and Squire (1999)
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EP cannot navigate from his current home to a
different location (anterograde amnesia)
Teng and Squire (1999)
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EP has intact remote spatial memory
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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NEOCORTICAL AREAS
HIPPOCAMPUS
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Significance of Retrograde Amnesia

• The hippocampus is initially critical for memory,
  but over time memories eventually become
  independent of the hippocampus.
• Memories are eventually consolidated within the
  neocortex

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Squire 1992
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Features of Habit Learning system

• Learning occurs slowly over time
• Stimulus-response
• In humans, learning does not require conscious
  awareness of the contingencies
• Supported by the neostriatum!

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Neostriatum
CAUDATE NUCLEUS
PUTAMEN
SUBSTANTIA NIGRA
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The Weather Task Probabilistic classification
task
Knowlton et al., (1996)
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Do these cards predict sun or rain?
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Parkinsons disease patients are impaired at
learning the weather task but amnesic patients
are not
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LONG-TERM MEMORY
DECLARATIVE (EXPLICIT)
NONDECLARATIVE (IMPLICIT)
SEMANTIC (facts)
EPISODIC (events)
Hippocampus/ Medial Temporal Lobe
Squire 1992