(2004). Functional amnesia

Download Report

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
memory consolidation: a neurobiological perspective. Current
Opinion in Neurobiology 1995, 5:169-177
Squire, L. (1982). THE NEUROPSYCHOLOGY OF HUMAN
MEMORY. Department of Psychiatry, University of California
at San Diego, School of Medicine, La Jolla, California 92093
Moss, M. (2009). Animal Models of Amnesia. Boston
University School of Medicine, Boston MA
Squire, L. & Zola-Morgan, S. (1990). The Neuropsychology of
Memory Parallel Findings in Humans and Nonhuman Primates.
Veterans Affairs Medical Center Sun Diego, California 92161
and Department of Psychiahy University of California San
Diego, La Jollu, California 92093
Race, E. & Verfaellie , M. (2012). Amnesia and the Brain.
Boston: Elsevier Inc.