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

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