Transcript Document

Human Brain Disorders and Memory
Nicola J. Broadbent Ph.D
Dept. Psychiatry
UCSD School of Medicine
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
H.M.’s
presumed
H.M’s
Lesion lesion
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
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”.
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.
“Everyday is alone in itself, whatever enjoyment I’ve
had, and whatever sorrow I’ve had. 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.
Its like waking from a dream, I just don’t remember”
(p. 217; Milner et al., 1968)
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”.
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
Damage to the medial temporal lobe does not impair
mirror drawing (nondeclarative/implicit learning)
Why is H.M.’s case so important?
1.
Provided first strong evidence for the role of the medial
temporal lobe structures in long-term memory (LTM)
2.
Showed that memory was dissociable from other cognitive
abilities
3.
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
LONG-TERM MEMORY
DECLARATIVE
(EXPLICIT)
EPISODIC
(events)
NONDECLARATIVE
(IMPLICIT)
SEMANTIC
(facts)
SIMPLE
PROCEDURAL
CLASSICAL
(SKILLS & HABITS)
CONDITIONING
FEAR
NONASSOCIATIVE
PRIMING
LEARNING
&
PERCEPTUAL
LEARNING
SOMATIC
AMYGDALA
CEREBELLUM
STRIATUM
REFLEX
NEOCORTEX
PATHWAYS
Hippocampus/
Medial Temporal Lobe
Squire 1992
Declarative Memory vs. Nondeclarative memory
Declarative Memory
Nondeclarative 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)
• 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
Neural Substrate of Declarative Memory
S
MTL
CA1
HIPPOCAMPAL
REGION
CA3
DG
OTHER DIRECT
PROJECTIONS
ENTORHINAL
CORTEX
PERIRHINAL
CORTEX
PARAHIPPOCAMPAL
CORTEX
UNIMODAL AND POLYMODAL ASSOCIATION AREAS
(Frontal, temporal, and parietal lobes)
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.
Rey-Osterrieth Complex Figure
Damage to the Hippocampus Impairs Recall of ReyOsterrieth Complex Figure
Subjects with medial temporal lobe damage are
severely impaired at recalling the Rey-O figure.
• Case RB demonstrates that damage restricted to the
hippocampus is sufficient to result in anterograde
amnesia
• RB’s amnesia is milder than HM, suggesting that
other medial temporal lobe regions also make
significant contributions to memory.
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.
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)
Subjects with damage to the MTL are impaired at
recognition tasks (vision, sound, odor)
NONSENSE SOUNDS
PREFERENCE FOR NOVEL
OBJECT (%)
VISUAL PAIRED COMPARISON
70
60
ODOR
50
0.5 sec
2 min
DELAY
McKee RD, Squire LR (1993)
2 hr
Declarative Memory: Retrograde Amnesia
CASE E.P
• Developed amnesia after contracting viral encephalitis
• MTL severely damaged
• Severe anterograde amnesia
• Temporally limited retrograde amnesia
Like H.M, E.P has normal IQ, perception and other
cognitive abilities
E.P’s working memory is normal
E.P has severe Anterograde Amnesia
E.P has severe Anterograde Amnesia
C
B
D
A
Teng and Squire (1999)
EP can navigate around his childhood neighborhood
demonstrating intact remote spatial memory
100
90
Percent Cor rect
80
70
2
1
1
2
2
1
60
50
40
30
20
10
0
Familiar
Navigation
Novel
Navigation
Alternate
Routes
Teng and Squire (1999)
EP cannot navigate from his current home to a different
location (anterograde amnesia)
100
90
Percent Correct
80
70
60
50
EP
CON
40
30
20
10
0
Current
Neighborhood
Teng and Squire (1999)
EP has intact remote spatial memory
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
NEOCORTICAL AREAS
HIPPOCAMPUS
Significance of Retrograde Amnesia:
• The hippocampus is initially critical for memory,
but over time memories eventually become
independent of the hippocampus.
CORRECT (%)
• Memories are eventually consolidated within the
neocortex
NEW
OLD
MEMORY
NONDECLARATIVE
(IMPLICIT)
SIMPLE
CLASSICAL
CONDITIONING
FEAR
PROCEDURAL
(SKILLS & HABITS)
PRIMING
&
PERCEPTUAL
LEARNING
NONASSOCIATIVE
LEARNING
SOMATIC
AMYGDALA
REFLEX
STRIATUM
CEREBELLUM
NEOCORTEX
PATHWAYS
Squire 1992
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!
Neostriatum
CAUDATE
NUCLEUS
PUTAMEN
SUBSTANTIA
NIGRA
The Weather Task: Probabilistic classification task
Knowlton et al., (1996)
Do these cards predict sun or rain?
Parkinson’s disease patients are impaired at learning
the weather task but amnesic patients are not
LONG-TERM MEMORY
DECLARATIVE
(EXPLICIT)
EPISODIC
(events)
NONDECLARATIVE
(IMPLICIT)
SEMANTIC
(facts)
SIMPLE
PROCEDURAL
CLASSICAL
(SKILLS & HABITS)
CONDITIONING
FEAR
NONASSOCIATIVE
PRIMING
LEARNING
&
PERCEPTUAL
LEARNING
SOMATIC
AMYGDALA
CEREBELLUM
STRIATUM
REFLEX
NEOCORTEX
PATHWAYS
Hippocampus/
Medial Temporal Lobe
Squire 1992