Transcript (2004). Functional amnesia

Amnesia
Danielle Noftle
Neuropsychology of Abnormal Behaviour
November 19th/2015
Presentation Outline
Introduction
 History: Patient H.M.
 Categories of Amnesia
 Memory Consolidation
 Neurotransmission
 Squire's Taxonomy of memory
 Neuroanatomy
 Neuroendocrinology
 Animal Models/Assessment

Introduction
Amnesia: a condition in which memory (either stored
memories or the process of committing something to
memory) is disturbed or lost
 Different from everyday forgetting or absentmindedness
 Organic or neurological causes (i.e. damage from
physical injury)
 Functional or psychogenic causes (i.e. PTSD)
Atkinson-Shiffrin Model of Memory
History: Patient H.M. (1953)

Most widely studied clinical case of amnesia to
date

Doctor's bilaterally resected his medial
temporal lobes
 Removals
extended posteriorially for approx.
8cm - included uncus, amygdala, hippocampal
gyrus and anterior 2/3's of hippocampus
Patient H.M
 Surgery
treated his epilepsy BUT
destroyed his ability to form new LTMs
 Severely
 BUT
impaired his episodic memory
H.M. had above average intelligence
 Performed
normally on standard tests of
perception, short term memory and
language comprehension
Patient H.M.
https://www.youtube.com/watch?v=KkaXNvzE4pk
Types of Amnesia
1) Infantile Amnesia: common inability of adults to
remember the earliest years of their childhood, typically
from birth until around four years old
Types of Amnesia
2) Global Amnesia:

Patients can appear normal to casual observation

Normal intellectual capacity, digit span and intact social
skills

Defect lies in retaining new memories and in recalling
memories acquired just before amnesia
Examples of Global Amnesia:
A. Wernicke-Korsakoff Syndrome (WKS)
• Caused by thiamine deficiency due to chronic
alcohol abuse - thiamine helps produce energy
needed for proper neuronal function
• After passing of acute stage - patient is alert and
responsive, and has normal intellectual capacity
Korsakoff Brain
B. Bilateral Electroconvulsive Therapy
• Prescribed for treatment of severe depression
• Amnesia is common side effect but often
temporary
Categories
3) Psychogenic amnesia:

A.k.a. functional amnesia or dissociative amnesia

characterized by abnormal memory functioning in the
absence of structural brain damage or a known
neurobiological cause
DSM-V: Dissociative Amnesia Criteria
Unable to recall autobiographical memory associated
with a traumatic event
 The recall of traumatic events is usually unconscious
 The inability to recall traumatic events creates distress
 The memory dysfunction does not have a physiological
cause
 The memory dysfunction is not dissociative identity
disorder
 The memory loss is not a result of substance abuse or
other substance

Categories
4) Amnesia from DIFFUSE brain damage
 damage to several areas of the brain
 often caused by closed brain injuries, Korsakoff
syndrome etc
5) Amnesia from FOCAL brain damage
 confined to one area of the brain
 brain tissue is damaged at the site where the injury
occurred (ex. surgery)
Anterograde Amnesia

Inability to remember events and facts encountered after
the onset of illness

Caused by damage to hippocampus, fornix, or mammillary
bodies

More common in amnesic patients than retrograde amnesia

Intact intelligence, personality and judgment but day-today functioning is poor

Recent events aren't transferred to long term memory
(encoding)
Retrograde Amnesia

Inability to remember events that occurred prior to
injury (retrieval)

Caused by damage to medial temporal lobe,
diencephalon, and basal forebrain

Ribot's Law: retrograde amnesia is characterized by
a time gradient (a.k.a. temporally graded amnesia)


occurs because memory for recent events is more fragile
than memory for remote events
Lead to discovery of memory consolidation
Memory Consolidation

Process of stabilizing a memory trace after the
initial acquisition

Begins at synaptic level - brain forms new pathways
to the information it encounters

Involves reorganization in nervous system:

Level 1: synaptic consolidation - occurs rapidly at the
site of synapses

Level 2: systems consolidation - gradual reorganization
of circuits within brain regions
Memory Consolidation: Stages




1) information is bound to a memory trace by the
hippocampus
2) initial binding involves a short-term consolidation
process - a.k.a cohesion (completed within seconds
to minutes)
3) long-term consolidation begins: hippocampus is
needed for initial storage and recovery
4) neocortex then sustains permanent memory trace
and mediates its retrieval
Memory Consolidation
Reactivation: Major mechanism of consolidation
 Occurs during sleep or periods of relaxed
wakefulness
 Hippocampus replays neural activity associated with
memory
 Activity occurs in network connecting hippocampus
and cortex
 Results in formation of connections between
cortical areas
Neurotransmission: Long-Term
Potentiation

Important process of memory consolidation

LTP refers to enhanced firing of neurons after
repeated stimulation

First time neuron 'A' is stimulated, neuron 'B'
fires slowly

BUT after repeated stimulation, neuron 'B'
fires much more rapidly to same stimulus
Glutamate and LTP

Glutamate binds to the receptors for AMPA and NMDA
- both are extremely important for LTP

When binded with AMPA: sodium ions enter the postsynaptic neuron.

Increase in sodium causes depolarization

When depolarization triggers an action potential - nerve
impulse is transmitted to the next neuron
Glutamate and LTP

When binded with NMDA:
 admits
calcium ions into the post-synaptic cell
 BUT
at resting potential - the calcium channel is
blocked by magnesium ions
 so
even if glutamate binds to the receptor, calcium
cannot enter the neuron
 For
magnesium ions to leave the channel, the
dendrite’s membrane potential must be depolarized
Glutamate and LTP
 after
sustained activation AMPA postsynaptic neuron becomes depolarized
 magnesium
then withdraws from the
NMDA receptors and allows large
numbers of calcium ions to enter the cell

increased concentration of calcium makes
this synapse more efficient for an
extended period
Demonstration: Long Term Memory Encoding and Retrieval
Read the following words:
Apple, desk, shoe, sofa, plum, chair, cherry,
coat, lamp, pants, grape, hat, melon, table,
gloves
Now write down as many as you can
Demonstration
Look at the list you created and notice whether
similar items (ex. apple, plum) are grouped
together - if so, supports idea of a retrieval cue: a
word or other stimulus that helps a person
remember information stored in memory for other
words in that category
Squire's Taxonomy of Memory
2 separate memory systems:
1) Explicit or Declarative Memory
 Info is available later as a conscious recollection
 Includes semantic (facts) and episodic (events) memory
 Episodic memory is lost in amnesia - Patient H.M.
 Capacity for declarative memory depends on damage to
hippocampus and surrounding structures
Squire's Taxonomy of Memory
2) Implicit or Nondeclarative Memory
 Spared (nondeclarative) memory abilities do not
depend on hippocampal structures
 Includes procedural memory, priming and perceptual
learning, classical conditioning and nonassociative
learning
 They all reflect ways in which performance can
change as the result of experience, but without a
conscious recollection of any previous event or fact
Neuroanatomy:
Medial Temporal Lobe
Includes:

Perirhinal Cortex

Parahippocampal Cortex

Entorhinal Cortex

Hippocampus
Medial Temporal Lobe

Structures of MTL have
reciprocal connections
with neocortex

MTL binds distributed
storage sites together in
neocortex that represent
a whole memory
Medial Temporal Lobe


Supports capacity for conscious recollections of
facts and events (explicit memory)
Role of the MTL is only temporary
 damage
to the MTL produces temporally
graded retrograde amnesia
Fields of the Hippocampus
1) Dentate Gyrus (DG) - tightly packed layer of
small granule cells
 2) Cornu Ammonis (CA) areas: CA4, CA3, CA2 &
CA1 - filled with densely packed pyramidal cells
(like those found in neocortex)
 3) Subiculum
 4) Presubiculum and parasubiculum
 5) Then a transition to entorhinal area of the
cortex

Hippocampus Fields and Memory

Lesion to CA1 area of hippocampus breaks the chain of
information-processing

Has huge influence on the functioning of the
hippocampal formation
 Subicular
complex and entorhinal cortex are main
sources of output from the hippocampus to
subcortical structures
Amygdala

Encodes emotional aspects of memory

The basolateral complex of the amygdala
(BLA) - moderate concentration of
glucocorticoid receptors (GRs)

BLA is involved in mediating glucocorticoid
effects on memory consolidation
Amygdala

A GR agonist infused into the BLA after training
enhances memory consolidation

Vs. lesions or inactivation of the BLA which blocks
memory-enhancing effects of glucocorticoids

Modulation hypothesis: after an emotionally arousing
experience amygdala engages stress-related hormones
and neurotransmitters to enhance memory consolidation
Neuroendocrinology: Stress and Amnesia
 Stress
activates the hypothalamus–pituitary–
adrenal (HPA) axis
 results
in the release of glucocorticoid
hormones from the adrenal cortex
 Acute
elevations in glucocorticoids enhance
the consolidation of new information BUT
impairs the retrieval of already stored
information
 Chronically
elevated glucocorticoid levels results
in a cumulative strain on hippocampal function
HPA Axis
Stress and Amnesia

adrenal cortex synthesizes GCs from available
cholesterol and secretes cortisol into the
bloodstream

approximately 95% of secreted cortisol becomes
bound to proteins (such as globulin and albumin)

remaining cortisol is free to bind to receptors in
cortical and subcortical structures (including the
hippocampus, amygdala, hypothalamus and pituitary)
Stress and Amnesia
Glucocorticoid effects on memory consolidation

Glucocorticoid effects on memory consolidation follow
an inverted U-shape
 moderate
doses enhance memory vs. higher doses
are less effective or may even impair memory
consolidation
Animal Studies
1) Match-to-sample Tasks

Developed during era of behaviorism

Animal (often pigeon) presented with a colored stimulus
sample

It would then proceed to peck at sample

Bird is then presented with two comparison stimuli - one
comparison stimulus matches the sample (same color)
and the other doesn't

If bird pecks the matching comparison then it is
rewarded
Animal Studies
2) Delayed matched-to-sample
 very similar to match-to-sample tasks
 only difference - before choosing the correct
response there is a short delay
 delay can vary in length - determines how long
animal can retain information in their working
memory
 If animal responds correctly over fifty percent
of the time - it shows that it has retained
information
Chimp Vs. Human! Working Memory
Test
https://www.youtube.com/watch?v=zsXP8qeFF6A
Assessment
Wechsler Memory Scale
 original WMS consisted of seven subtests
 assessed orientation, span of attention, immediate
recall of stories and novel geometric figures, and
the ability to learn paired words
 BUT there were many critiques: validity,
standardization and psychometric properties
 WMS-Revised was then created
 5 standardized scores were computed: general
memory, attention-concentration, verbal memory,
visual memory, and delayed recall
Assessment
Verbal Tests
 Digit Span
 examiner presents increasingly long sequences of digits
 examinee is then asked to repeat each sequence in the
same order presented
 Once a maximum digit span is achieved in the forward
direction the examinee is asked to repeat backward
 Immediate recall span
 Repetition of information immediately after it's
presentation
References

Amy L. Alderson & Thomas A. Novack (2002) Neurophysiological and Clinical
Aspects of Glucocorticoids and Memory: A Review. Journal of Clinical and
Experimental Neuropsychology, 24:3, 335-355

Bliss, T. V. P., & Collingridge, G. L. (1993) A synaptic model of memory: long
term potentiation in the hippocampus. Nature Publishing Group.

John P. Aggleton & Richard C. Saunders (1997) The Relationships Between
Temporal Lobe and Diencephalic Structures Implicated in Anterograde
Amnesia, Memory, 5:1-2, 49-72, DOI: 10.1080/741941143

Marie D. Sauro, Randall S. Jorgensen & C. Teal Pedlow (2003) Stress,
Glucocorticoids, and Memory: A Meta-analytic Review, Stress, 6:4, 235245

Kritchevsky, M., Chang, J., & Squire, L. R. (2004). Functional amnesia:
Clinical description and neuropsychological profile of 10 cases. Learning &
Memory, 11(2), 213-226. doi:http://dx.doi.org/10.1101/lm.71404

McCann, D. & Weiten, W. (2013). Psychology Themes and Variations. Nelson
Education.
References

Zola-Morgan, S., Squire, L. R., & Mishkin, M. (1982). The neuroanatomy of
amnesia: Amygdala-hippocampus versus temporal stem. Science,
218(4579), 1337-1339. Retrieved from
http://ezproxy.library.yorku.ca/login?
url=http://search.proquest.com/docview/616757258?accountid=15182

de Quervain, D. J. -., Aerni, A., Schelling, G., & Roozendaal, B. ( (2009).
Glucocorticoids and the regulation of memory in health and disease.
Frontiers in Neuroendocrinology, 30(3), 358-370.
doi:http://dx.doi.org/10.1016/j.yfrne.2009.03.002

Goldstein, B. E. (2011). Cognitive Psychology: Connecting Mind, Research,
and Everyday Experience. Wadsworth, Cengage Learning

Roozendaal, B. (2002). Stress and Memory: Opposing Effects of
Glucocorticoids on Memory Consolidation and Memory Retrieval.
Department of Neurobiology and Behavior, University of California,
Irvine, California 92697-380. doi:10.1006/nlme.2002.4080

Squire, L. (2004). Memory systems of the brain: A brief history and
current perspective. Departments of Psychiatry, Neurosciences, and
Psychology, University of California, San Diego, La Jolla, CA 92093, USA
References





Alvarez, P. & Squire, L. (1995) Retrograde amnesia and
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