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Memory and Amnesia


Speaking, bicycling, multiplication by 7s, urinary control, taste of oranges, ... Fuster, 1989. Single cell recording from DLPFC. Delayed-response task ... – PowerPoint PPT presentation

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Title: Memory and Amnesia

Memory and Amnesia
  • Lecture 7
  • March 7th, 2006

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
  • Alzheimers Disease, Traumatic Brain Injury,
    Schizophrenia, Epilepsy, Dementia, Strokes,
    Tumors etc.

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

What is Learning and Memory?
  • Learning relatively permanent change in an
    organisms 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).

Stages in Memory Formation and Retrieval
  • 1. Encoding processing of incoming information
  • Acquisition registers inputs in sensory
    buffers Consolidation creation of a strong
    representation over time
  • 2. Storage the result of acquisition and
  • 3. Retrieval utilizes stored information to
    crate a conscious representation or to execute a
    learned behavior

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 division
  • Semantic (general knowledge)
  • Episodic (personal memories)
  • Skills

Patient H.M.
  • 1953 William Scoville Brenda Milner
  • William Scoville - bilateral medial temporal lobe
  • Brenda Milner neuropsychologist
  • No language or perceptual deficits or motor
  • IQ unchanged (118)
  • Intact digit span short-term memory can hold a
  • No language or perceptual deficits
  • Remembered who he was
  • Severe memory impairment - amnesia

What is Amnesia?
  • Amnesia - partial or total loss of memory
  • Infantile amnesia
  • Fugue 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

Temporal Extent
  • Anterograde amnesia
  • Retrograde amnesia
  • H.M.?

Temporal Gradient
  • Temporal gradient a gradient in memory loss in
    which recent memories are affected to a greater
    degree than more remote memories
  • Ribots Law
  • First-in-last-out (e.g., childhood memories)
  • Alzheimers disease

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Global Nature of the Deficit
  • In genera, in cases of amnesia, memory deficit is
  • However, there are cases of modality specificity
  • For example, left hippocampal damage is
    associated with verbal memory deficits

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

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

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

There are at least 2 types of short-term memory
  • Phonological loop deals with verbally based
  • Visuospatial sketchpad deals with object forms
    and locations

Short Term Memory
Spatial Working Memory Spatial Span
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

  • Pursuit-rotor task
  • Priming - The Gollin Incomplete Picture task

Two Kinds of Long-Term Memory
  • Explicit conscious, intentional recollection of
    previous experience
  • Declarative
  • Fact
  • Memory
  • Knowing what
  • Implicit unconscious, non-intentional form of
  • Non-declarative
  • Skill
  • Habit
  • Knowing how

Are There Different Types of Explicit Memory?
Interview of G.O. by Dr. Levine
  • Do you have a memory of when you had to speak in
  • Well yes, Im 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.

  • 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.

  • But this was something ongoing, so every training
    session you would tell people this, right?
  • Yes
  • So what were 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 were asking is do you remember one
    time you gave a talk?
  • Oh! Yes I do.

  • 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.

  • Im getting the impression that you have a really
    good memory for all the training that youve done
    but you dont 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.

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

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

Can People with Amnesia Lear New Semantic
  • 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

Summary of Major Points Hippocampal Amnesia
  • Global anterograde amnesia
  • Explicit memory (episodic semantic)
  • Graded retrograde amnesia
  • Ribbots law
  • Intact implicit memory
  • Motor learning
  • Priming
  • Intact short term memory

The Role of Hippocampus in Memory
  • H.M. case led neuropsychologist to focus on the
  • 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

The Anatomy of The Hippocampus
  • Two gyri Ammons 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.

Entorhinal cortex
Perirhinal cortex
Perahippocampal cortex
Association neocortex
Memory and the Hippocampus
  • Hippocampus as a storage site for memory?
  • Hippocampus consolidates new memories?

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

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??

Case Histories of Hippocampal Function 1
  • 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

Hippocampus and the Context
  • Episodic memory is context dependent
  • Associations between faces, names, places,
    events, time etc.
  • Therefore, it has been suggested that the
    hippocampus is important for contextual learning
    (relations between items)

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 impaired on this test

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 items are moved
  • Hippocampal patients
  • Reduction in movements after identical repeat
  • No increase in movements if items are moved

Hippocampus and Relational Learning
  • Spatial memory - hippocampal lesions impair
    performance (Morris et al., 1982)

Hippocampus and Relational Learning
  • Egocentric Learning no impairment after
    hippocampal lesions (Eichenbaum et al., 1990)

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
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
  • Alzheimers 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

The Role of Diencephalon - Korsakoffs Syndrome
  • Damage to diencephalon (dorsomedial thalamus and
    mammillary bodies) causes amnesia
  • Strokes, tumors, trauma, and metabolic problems
    (associated with alcoholism) (vitamin B1
  • Korsakoffs syndrome 1) retrograde amnesia, 2)
    anterograde amnesia, 3) lack of insight, 4)
    apathy, 5) meager content in conversation, 6)
  • Confabulations the recitation of imaginary
    experiences to fill gaps in memory

The Neural Basis of Explicit Memory
Neural Mechanisms for Episodic Memory
The Neural Basis of Implicit Memory
  • Patient J.K. Parkinsons 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. Ive done this in my life, and now I cant
    remember how to do it!
  • Huntingtons Chorea (degeneration of basal
    ganglia cells) mirror drawing task no

The Neural Basis of Implicit Memory
  • Motor-based implicit memory is thought to be
    mediated by a circuit separate from limbic
    structures (explicit memories)

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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