Memory and Amnesia

1
Memory and Amnesia

• Lecture 7
• March 7th, 2006

2
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
• Alzheimers Disease, Traumatic Brain Injury,
  Schizophrenia, Epilepsy, Dementia, Strokes,
  Tumors etc.

3
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

4
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).

5
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
  consolidation
• 3. Retrieval utilizes stored information to
  crate a conscious representation or to execute a
  learned behavior

6
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

7
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

8
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

9
Temporal Extent

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

10
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

11
(No Transcript)
12
Global Nature of the Deficit

• In genera, 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

13
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

14
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

15
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

16
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

17
Short Term Memory
Spatial Working Memory Spatial Span
1
3
5
4
6
2
18
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

19

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

20
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

21
Are There Different Types of Explicit Memory?
22
Interview of G.O. by Dr. Levine

• Do you have a memory of when you had to speak in
  public?
• 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.

23

• 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.

24

• 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.

25

• 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.

26

• 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.

27
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

28
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

29
Can People with Amnesia Lear New Semantic
Information?

• 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

30
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

31
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

32
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.

33
Hippocampus
Hippocampus
Entorhinal cortex
Perirhinal cortex
Perahippocampal cortex
Association neocortex
34
Memory and the Hippocampus

• Hippocampus as a storage site for memory?
• Hippocampus consolidates new memories?

35
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

36
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??

37
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

38
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)

39
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

40
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

41
Hippocampus and Relational Learning

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

42
Hippocampus and Relational Learning

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

43
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
44
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

45
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
  deficiency)
• Korsakoffs 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

46
The Neural Basis of Explicit Memory
47
Neural Mechanisms for Episodic Memory
48
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
  improvement

49
The Neural Basis of Implicit Memory

• Motor-based implicit memory is thought to be
  mediated by a circuit separate from limbic
  structures (explicit memories)

50
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
51
(No Transcript)