AmnesiaDanielle 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 absent-
mindednessOrganic 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 impaired his episodic memoryBUT 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 Amnesia1) 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-to-day 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 post-synaptic 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 Memory2 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 Studies2) 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, 235-245
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.
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