Memory and Amnesia
Nathan Spreng
Cognitive Neuroscience: PSY393
August 2, 2005
Amnesia at the movies
Remember Sammy Jankis?
Memory Lecture Summary
• Memory
– Process and Definitions
– Systems
• Medial Temporal Lobe & Classic Amnesia
– Encoding & Retrieval
– Case studies
• Frontal Lobes
– Working Memory & DLPFC
– Working with Memory
– Case study
• Autobiographical Memory
Memory is...
• A group of mechanisms or processes by
which experience shapes us, changing our
brain and behaviour
• The product of learning
Memory involves...
• Acquisition
• Retention
• Ability to retrieve
– information
– personal experiences
– procedures (skills and habits).
Memory enables...
• Adaptation to the environment
• Improvement of our interactions with the
outside world
• Intergenerational transfer of knowledge
Short and Long Term Memory
• Memory can be divided into
– Time (seconds to minutes to years)
– Contents (7 plus minus 2)
– Systems by type of information
Memory processes
1. Registration
2. Encoding
3. Consolidation
4. Storage
5. Retrieval
6. Re-encoding
Sensory perception in sensory brain
areas
Initial processing (association with
previous information) - Trace
Deeper processing:
Engram formation
Stable representation in central
nervous system
Reproduction of previously stored
information: Recollection
Re-encoding through retrieval;
initial trace (engram) changes
Memory Systems
Memory Systems
• Implicit Memory: Memory without
awareness
– Skills, priming, etc (spared in amnesia)
• Explicit Memory/Declarative Memory
– Memory accompanied by an awareness of
recollection. May be “declared” or verbally
reported
Amnesia
Definition: “An abnormal mental state in which
memory and learning are effected out of all
proportion to other cognitive functions in an
otherwise alert and responsive patient”
Kopelman (2002)
• Memory can be compromised in isolation from
other cognitive abilities
• Amnesia is selective, effecting certain capacities,
showing that there are many systems of memory
Temporal Extent of Amnesia
• Anterograde amnesia
– Deficit in new learning
– Inability to form new memories AFTER time of
injury
• Retrograde amnesia
– impairment of memory of information PRIOR
to onset of amnesia
– temporal gradient, effecting recent > remote
Temporal Extent of Amnesia
• Ribot’s Law (1882): “The progression of
the destruction of memory follows a logical
order. It begins with the most recent
recollections, being rarely repeated, and
having no permanent associations”
• Greater compromise of recent memory over
remote
Temporal Extent of Amnesia
The case of H.M.
• HM - surgery for intractable
epilepsy.
• Resection of hippocampus,
parahippocampal gyrus,
amygdala & uncus.
• HM could not form new
memories (anterograde
amnesia).
• Retrograde amnesia (11 years)
• Right: HM vs. 66-yr old
Control
Anterior
Posterior
(Corkin et al., 1997)
Etiology of Amnesia
•
•
•
•
•
•
•
Korsakoff’s syndrome (Jimmy)
Herpes encephalitis (Clive)
Severe hypoxia
Vascular disorders
Head Injury (K.C.)
Dementia (J.S.)
Transient global amnesia (fugue state)
Amnesia
• Inability to form new long term
memories
• Assessed with
– Free recall (no info)
– Cued recall (starting with “c”)
– Recognition (target and lures used)
• Savings in relearning (also impaired in
amnesia)
Memory Systems
Impaired
Spared
Implicit Memory
•
•
•
•
“Memory without awareness”
Spared in classical amnesia
Priming – Primary Sensory Cortex
Procedural Memory - Striate
Implicit Memory
• Gollin Incomplete
Pictures task
• Repetition Priming
• Bias to previous
exposure
Implicit Memory
• Eye movements to
assess implicit
memory
• Top: Initial exposure,
eye movements over 3
items
• Bottom: 2nd exposure,
eye movements over
where one item would
be
Implicit Memory
• Procedural Memory
Mirror Reading Task
• Improvement in
performance without
recollection of the
material
• Spared in amnesia
Declarative Memory
• Semantic Memory:
“Knowing”
– Knowledge of words and
their meanings, objects,
concepts and facts.
• Episodic Memory:
“Remembering”
– Re-experiencing of an event
that occurred in the past
including time and place of
original encoding
episode…mental time travel.
The case of K.C.
K.C.
• TBI
• Bilateral hippocampus
& frontal lobe damage
• Severe RA and AA
• No episodic memory
• Intact semantic
memory
normal
Memory Circuit
(Mayes, 2000)
Main memory structures & connections
Diencephalon
MTL
1. Perirhinal cortex
Mamillary bodies
2. Entorhinal
cortex
Hippocampal
formation
3. Parahippocampal
cortex
Subiculum
CA1
CA2
CA3
Dentate gyrus
Structures of the Medial Temporal Lobe
1-3 =
Parahippocampus
Medial Temporal Lobe
• Hippocampus as Convergence zone
• Memories are not stored within the
hippocampus
• Hippocampus acts as an “indexor” and lays
trace of memories.
• Memories are stored in sensory cortex
• Hippocampus has access to all sensory
information
• Relational Memory
Medial Temporal Lobe
• Morris Water Maze
• Hippocampal lesions
• Deficits in learning
and remembering
spatial relations
Medial Temporal Lobe
• Hippocampal Lesions:
Material specific
memory disorder
• Unilateral
– Left: verbal
impairment
– Right: nonverbal
impairment
• Bilateral - Global
impairment
• fMRI Hippocampus:
Material dependent
activity at encoding
• Verbal - Left
• Nonverbal - Right
Medial Temporal Lobe
• Hippocampal activity predicts successful
recall
– During encoding
– During retrieval (Nyberg, et al., 1996)
• “Subsequent Memory Effect”
Medial Temporal Lobe
• While memories are young, they depend
upon an intact hippocampus
• Are old episodic memories independent
hippocampus once consolidated?
Medial Temporal Lobe
• fMRI: Robustness of hippocampal activity
during retrieval related to vividness of
memory, not age (Gilboa, 2003)
• H.M. possesses some remote memories.
– Are they episodic? Depends on measure
– lack episodic content, “semanticized” (Steinvorth
& Corkin, submitted)
Medial Temporal Lobe
• How does the
hippocampus bind
information?
• LTP
– Hebb’s Law
• Connectivity
(Rolls, 2000)
• Same brain regions
activated for perception
and retrieval
• Regions
– fusiform gyrus (a)
– superior temporal gyri (d)
• Retrieval of pictures and
sounds, respectively
(2004) Proc. Natl. Acad. Sci. USA 101, 5181
MTL & Emotion
• Emotionality enhances memory
performance
• Mediated by the Basolateral limbic circuit
• Parahippocampus and perirhinal cortex
connect with the amygdala
• Orbitofrontal cortex involved in processing
salience at encoding
• Emotion enhances attention
Main memory structures & connections
Amygdala
Basolateral limbic
circuit
Mayes, 2000
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Video: NoT cue 17-27 minutes
Video: Tulving/Milner – Clive cue 6-18 minutes
Clive Wearing
• R-handed
• Above average IQ
• Prominent Musician
• Herpes Simplex
Encephalitis
• Bilateral temporal
lobe degeneration
L>R
• Dense Anterograde
Amnesia
(Wilson & Wearing, 1995)
Clive Wearing
Frontal Lobes
• Tennessee Williams:
“Life is all memory except for the present
moment that flies by so quickly that you can
hardly catch it going by”
• WM: moment
• LTM: past
Working Memory
• Central Executive: Attentional
control of the slave systems:
– Visuo-spatial sketchpad
– Phonological loop
• Both derive and feed
information to and from LTM
• WM is a combination of
maintenance and manipulation
operations and works in close
interaction with LTM
Baddeley & Wilson, 2002
Video: cue @ 27-33 min
Basic WM paradigms
•
•
•
•
•
•
•
Delayed response
Delayed alternation
Object alternation
Go No-Go
Reversal
Delayed match to sample
Delayed non-match to sample
– Recurring stimuli (recall most recent presentation)
– Trial-unique stimuli (distinguish familiar from novel)
Component processes of WM
• Mnemonic
– Register (encode)
– Store (maintain)
– Rehearse
• Non-Mnemonic
– Control interference (inhibit)
– Manipulate
– Select (retrieve, prepare)
– Respond (motor effector)
– Domain-specific sensory systems (spatial, object)
Working Memory
• Delayed Response Task:
– Access spatial information
– Hold information on on-line
during delay period
– Initiate motor response
• Delay tasks sensitive
to principal suclus
• Impaired with lesions
• Evidence for delayspecific neurons
Working Memory
• Shared working memory
circuit in humans
– BA9/46 (DLPFC)
– Posterior Parietal
– Left Hemisphere
• Delayed response
• Delayed alternation
• Object alternation
• “Guide behavior in the
absence of external cues”
Functional neuroimaging
(D’Esposito et al., 2000; Fletcher & Henson, 2001)
• DLPFC
–
–
–
–
Encoding (supraspan)
Maintenance
Manipulation
Scanning
encoding
• VLPFC
– Maintenance
– Rehearsal
– Inhibit, select
• Anterior PFC (Poles)
– More complex manipulation
manipulation
maintenance
CUE
DELAY
time
scanning
Inhibition/selection
RESPONSE
Frontal lobes and working with
memory
• Associative retrieval: conscious recollection
that are cue-driven
– medial temporal lobes (MTL)
• Strategic Retrieval: problem solving
approach to memory where
– the frontal lobes work with memories
– delivered through the medial temporal lobes
and posterior neocortex
Video: cue 35 minutes TRAIN
Frontal lobes and working with
memory
• Frontal-medial temporal interactions
– encoding
– retrieval
Simons & Spires (2003)
Frontal lobes and working with
memory
• Meta memory judgments
• Source amnesia
– Dissociation between item and contextual information
(details of study episode)
• Judgment of recency (Milner, 1971)
– Left-sided lesions affect verbal
– Right-sided lesions affect verbal and visual
• Temporal ordering (Milner, 1971)
Frontal lobes and working with
memory
• Confabulation
– Defined as an honest lying
– Requires retrieval, sequencing,
output monitoring
– Associative retrieval intact,
strategic retrieval impaired
– “Source amnesia magnified and
extended to include an entire
lifetime of experience”
(Moscovitch, 1989)
Schnider, 2003
Patient J.S.
Frontotemporal dementia
R
R
L
R
(McKinnon, et al., in preparation)
L
The case of JS: Confabulation
• MK: Can you tell me about Detroit again?
• JS: We were in this nice restaurant and a guy said I don’t
think you guys should go outside. There’s a sniper on the
roof outside. He said I think you had better stay in here.
I’ve just called the cops. (laughter) He said there’s a sniper
on the roof. He said you guys had better stay in here.
• MK: Then what happened?
• JS: Well the cops came. The cops got the guy. And they
said okay guys you can leave now. That was all the help
and we went outside.
Autobiographical Memory
• Memory of, or relating to, the self
• Involves episodic memory (ie autonoetic
awareness)
• Semantic memory
• Mental Time Travel
Autonoetic consciousness
Wheeler, Stuss & Tulving (1996); Tulving (2002)
Awareness of the self as a continuous entity
across time
"Remembrance is like a direct feeling; its object is
suffused with warmth and intimacy to which no
object of mere conception ever attains." James (1890)
"It's essence lies in the subjective feeling that the
present experience is of an earlier, similar one, and
in the belief that the self doing the experiencing
now is the same self that did it originally." Wheeler,
Stuss, & Tulving (1997)
Ascendancy of personal re-experiencing over
childhood amnesia
Bruce et al., 2000
Mental Time Travel:
Past & Future
Spreng & Levine (in press)
Autobiographical memory
Autobiographical recollection
Personal episodic versus personal semantic
b
a) Anteromedial prefrontal cortex
y = -56
e
b) Superior medial prefrontal cortex
d
c) Ventrolateral prefrontal cortex
a
d) Temporoparietal junction
f
e) Posterior cingulate/Precuneus
f) Thalamus (anterior nucleus)
x = -4
z= 5
c
Kopelman, 2002