Amnesia
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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.
