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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