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Transcript of 1 Memory and Amnesia Lecture 7 June 12th, 2006. 2 Learning & Memory “Life without memory is very...
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Memory and AmnesiaLecture 7June 12th, 2006
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Learning & Memory
“Life without memory is very unlike life as the rest of us know it; indeed, it is almost no life at all”
Speaking, bicycling, multiplication by 7s, urinary control, taste of oranges, balancing when standing, anxiety associated with public speaking, smell of bananas, the appearance of your face, your mothers name, first day of school………………
Alzheimer’s Disease, Traumatic Brain Injury, Schizophrenia, Epilepsy, Dementia, Strokes, Tumors etc.
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Lecture Outline:
Introduction Patient H.M. / Amnesia
Deficits Episodic vs. Semantic long-term memory
What is preserved? Short term memory Implicit memory
What is the role of the hippocampus in memory?
Basal ganglia and implicit learning
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What is Learning and Memory?
Learning – relatively permanent change in an organism’s behavior as a result of experience
Memory – is the acquisition and retention of, and the ability to retrieve information, personal experiences and procedures (skills and habits).
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Stages in Memory Formation and Retrieval
1.Encoding – processing of incoming informationAcquisition – registers inputs in sensory
buffers Consolidation – creation of a strong representation over time
2.Storage – the result of acquisition and consolidation3.Retrieval – utilizes stored information to crate a
conscious representation or to execute a learned behavior
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Are there Different Types of Memory? Temporal division
Sensory memory (milliseconds to seconds)Short-term/working/on-line (seconds to minutes)Long-term memory (minutes to years)
Content divisionSemantic (general knowledge)Episodic (personal memories)Skills
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Patient H.M. 1953 William Scoville & Brenda
Milner William Scoville - bilateral
medial temporal lobe resection Brenda Milner –
neuropsychologist No language or perceptual
deficits or motor deficits IQ unchanged (118) Intact digit span –short-term
memory – can hold a conversation
No language or perceptual deficits
Remembered who he was Severe memory impairment -
amnesia
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What is Amnesia?
Amnesia - partial or total loss of memory Infantile amnesiaFugue state Transient Global Amnesia – short-lived
neurologic disturbance characterized by memory loss (usually loss of old memories and an inability to form new memories) most often caused by ischemia
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Temporal Extent
Anterograde amnesia Retrograde amnesia H.M.?
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Temporal Gradient
Temporal gradient – a gradient in memory loss in which recent memories are affected to a greater degree than more remote memories
Ribot’s Law“First-in-last-out” (e.g., childhood
memories)Alzheimer’s disease
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Global Nature of the Deficit
In general, in cases of amnesia, memory deficit is multimodal
However, there are cases of modality specificity
For example, left hippocampal damage is associated with verbal memory deficits
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What Memory Functions are Spared in Amnesia?
Short-term/Working/On-line memory
Limited in capacity Consciously available Digit span - 7 ± 2 Serial position effect Primacy and recency
effect
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Dorsolateral Prefrontal Cortex and Working Memory
Delayed nonmatching to sample (DNMTS)
Monkeys with with DLPFC lesions perform poorly in this working memory task
Working memory does not depend on the hippocampus
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Brain Mechanisms of Working Memory
Fuster, 1989 Single cell recording from DLPFC Delayed-response task DLPFC neurons show sustained activity during the delay
until the response is made
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There are at least 2 types of short-term memory
Phonological loop – deals with verbally based memory
Visuospatial sketchpad – deals with object forms and locations
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Short Term Memory
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Spatial Working Memory
Spatial Span
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Implicit Learning
H.M. could learn new motor tasks
Could not remember doing the task before
Hence he ‘implicitly’ learned but could not ‘explicitly’ remember doing the task
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Pursuit-rotor taskPriming - The Gollin
Incomplete Picture task
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Two Kinds of Long-Term Memory
Explicit – conscious, intentional recollection of previous experience
Declarative Fact Memory Knowing what
Implicit – unconscious, non-intentional form of memory
Non-declarative Skill Habit Knowing how
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Are There Different Types of Explicit Memory?
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Interview of G.O. by Dr. Levine
Do you have a memory of when you had to speak in public?
Well yes, I’m was a call centre trainer with Modern Phone Systems, so I did a lot of speaking because I did a lot, a lot of training all across Canada. I also went to parts of the States.
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Do you remember one time that you were speaking? Can you tell us about one incident?
Oh yes! Well I trained thousands and thousands of clients on a wide variety of topics including customer service, inbound and outbound telemarketing. Handling difficult customers.
Do you remember one training session that you gave? Something that may have happened, a specific incident?
Well for example I always recommended that people take customer service first. And I always had people come up with four things about themselves, three that were true and one that was false. Not necessarily in that order.
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But this was something ongoing, so every training session you would tell people this, right?
Yes So what we’re looking for is one incident or one time
that you gave a training session or any other speech that you want to tell us about. A specific incident.
Oh well I customized a lot of material for many, many companies. And I also did lots of training at the home office
OK, so what we’re asking is do you remember one time you gave a talk?
Oh! Yes I do.
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One specific time not over a series of times, one time, can you tell us about that?
Oh sure yes, it was at the home office and yes, many many people were there
One occasion. When did it take place? When? Well I left Modern voluntarily in 1990. But this one occasion when did it take place? Ummm, well I started in the Modern home office.
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I’m getting the impression that you have a really good memory for all the training that you’ve done but you don’t seem to be able to come up with a specific talk that maybe stands out in your mind for any reason? Would you agree with that?
Oh yes well I always trained customer service. So there was no talk that maybe something
went wrong or something strange happened? No, no I was a very good trainer.
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Two Kinds of Explicit Memory
Episodic Memory (personal experiences)
Conscious awareness of past events
Autobiographical memory
Semantic Memory (facts about the world)
What is the capital of Italy? Are rock and animals the
same? Who are you parents? No episodic recollection of
the specific circumstances surrounding this learning
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Dissociation Between Episodic and Semantic Memory
Patient K.C. Motorcycle accident Subdural hematoma (a pool of blood under the dura
mater) was surgically removed Short-term memory OK Retrograde and anterograde amnesia All episodic memories have been lost Semantic knowledge has been preserved
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K.C. could learn new semantic information but could not remember how he learned it
Study: K.C. was given three-word sentences together with a related picture
Tested 12 months later: perceptual test or conceptual test
Hence, amnesics can acquire new semantic knowledge
Can People with Amnesia Lear New Semantic Information?
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Summary of Major Points – Hippocampal Amnesia
Global anterograde amnesiaExplicit memory (episodic; semantic)
Graded retrograde amnesiaRibbot’s law
Intact implicit memoryMotor learningPriming
Intact short term memory
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The Role of Hippocampus in Memory
H.M. case led neuropsychologist to focus on the hippocampus
However, H.M.’s brain resection included several structures (hippocampus, amygdala, perirhinal cortex) making conclusions difficult
40% of H.M.’s hippocampus seems to be intact
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The Anatomy of The HippocampusTwo gyri: Ammon’s horn
(CA1, CA2, CA3 and CA4) and dentate gyrus
Two major pathways connecting it to the rest of the brain: perforant path and fimbria-fornix.
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Hippocampus
Hippocampus
Entorhinal cortex
Perirhinal cortex Perahippocampal cortex
Association neocortex
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Memory and the Hippocampus
Hippocampus as a storage site for memory? Hippocampus consolidates new memories?
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The Hippocampus as a Storage Site for Memory?
If memories are stored in the hippocampus more remote memories should be as likely to be lost as recent memories
However, in most cases more remote memories, especially those acquired before the 20th year of life, seem to be spared
Most researchers do not think that the hippocampus is a place where memories are stored
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Hippocampus Consolidates New Memories?
According to this theory, hippocampus consolidates new memories
The memories are then stored somewhere else This would suggest that memories are held in the
hippocampus for a long time This would explain why older memories are usually
spared, whereas more recent memories are lost Problem is that retrograde amnesia can extend back
for decades Consolidation is very slow??
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More Consolidation Evidence
Patient R.B. –Dense anterograde amnesia - 1 to 2 years retrograde amnesia
Autopsy – overall hippocampus looked intact
Histological analysis indicated cell loss in CA1 region of the hippocampus
Conclusion: CA1 important for consolidation of new memories
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Hippocampus and the Context
Episodic memory is context dependentAssociations between faces, names, places,
events, time etc.Therefore, it has been suggested that
the hippocampus is important for contextual learning (relations between items)
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Hippocampus and Relational Learning
Paired-associate learning Apple-iron Horse-cow Children-sun Fault-squirrel Corkscrew-winter
At test: Apple-? Horse-? Children-? Fault-? Corkscrew-?
Amnesic patients are proportionally more impaired on this test
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Hippocampus and Relational Learning Eye movement while viewing pictures Target picture viewed
Same picture Same picture with altered item relations Novel picture
Intact subjects: Reduction in movements after identical
repeat Increase in movements if: novel picture
or if items are moved Hippocampal patients:
Reduction in movements after identical repeat
Increased movements for novel picture No increase in movements if items are
moved
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Hippocampus and Relational Learning
Spatial memory - hippocampal lesions impair performance (Morris et al., 1982)
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Hippocampus and Relational Learning
Egocentric Learning – no impairment after hippocampal lesions
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Knowing Where and Getting There
Maguire et al., (1998) investigated, with functional neuroimging, navigation through a virtual town
Hippocampus was activated if the regular route was blocked and the subjects had to find alternative routes
Maguire et al., 1998
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Anterior and Lateral Temporal Lobes and Memory
If memories are distributed throughout the cortex than damage to the cortex will lead amnesia
Lesions of the lateral cortex of the anterior temporal lobes (entorhinal and parahippocampal cortex also) produce retrograde amnesia
Alzheimer’s disease and herpes simplex encephilitis – anterograde and retrograde amnesia
Is this where the memory is stored? Medial temporal lobe - anterograde amnesia Temporal and frontal cortex – retrograde amnesia
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The Role of Diencephalon - Korsakoff’s Syndrome
Damage to diencephalon (dorsomedial thalamus and mammillary bodies) causes amnesia
Strokes, tumors, trauma, and metabolic problems (associated with alcoholism) (vitamin B1 deficiency)
Korsakoff’s syndrome: 1) retrograde amnesia, 2) anterograde amnesia, 3) lack of insight, 4) apathy, 5) meager content in conversation, 6) confabulations.
Confabulations – the recitation of imaginary experiences to fill gaps in memory
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The Neural Basis of Explicit Memory
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Encoding vs. RetrievalHERA Model
“Hemispheric encoding-retrieval asymmetry”
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Neural Mechanisms for Episodic Memory
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Patient J.K. – Parkinson’s disease (DA cells in substantia nigra die)
On one occasion, he stood at the door of his bedroom frustrated by his inability to recall how to turn on the lights. He remarked “I must be crazy. I’ve done this in my life, and now I can’t remember how to do it!”
Huntington’s Chorea (degeneration of basal ganglia cells) mirror drawing task – no improvement
The Neural Basis of Implicit Memory
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The Neural Basis of Implicit Memory
•Motor-based implicit memory is thought to be mediated by a circuit separate from limbic structures (explicit memories)
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Basal Ganglia and Habits
Using well learned routes (versus relying on a cognitive map) is associated with caudate (basal ganglia) activation
Maguire et al., 1998
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What is the relationship between the Medial Temporal Lobe (MTL) and Basal Ganglia (BG) Memory Systems?
MTL – episodic, declarative, relational memory (relation between multiple cues)
Basal ganglia – procedural, habit, nondeclarative (learning based on individual cues)
Are these two systems independent, cooperative or competitive?
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Relationship Between MTL and BG Memory systems?
Virtual environment 8-arm radial maze Extra maze cues (trees, landscape,
sunset, mountains) At the end of 4 arms there were objects
(not visible from the central platform) SPATIAL – USING AT LEAST 2
EXTRA-MAZE LANDMARKS (SPATIAL GROUP)
NON-SPATIAL – COUNTING THE ARMS FROM A SINGLE STARTING POINT (NON-SPATIAL GROUP)
Poldrack & Rodriguez, 2004
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Relationship Between MTL and BG Memory systems?
The use of a spatial strategy was associated with right hippocampal activation
The use of a non-spatial strategy was associated with caudate nucleus activation
In both cases there was activation in frontal cortex
Poldrack & Rodriguez, 2004
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Relationship Between MTL and BG Memory systems?
Win-shift task No particular stimulus is
consistently paired with the correct response (spatial learning)
Win-stay Single stimulus consistently paired
with the correct response Lit arms are baited
Packard et al., 1989
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Relationship Between MTL and BG Memory systems?
Packard et al., 1989
Win-shift task – Spatial task
Fornix lesions – deficits
Caudate lesions = control
Win-stay task – Non-Spatial task
Caudate lesions –deficits
Fornix lesions better than control