Stress & Memory


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Stress and memory-implications for stress related effects on memory

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Stress & Memory

  1. 1. Stress & Memory James M. DeCarli, PhD Candidate, MPH, MPA, CHES Departments of Psychology & Neuroscience University of Southern California
  2. 2. Overview Background on Stress History Types & Classifications Physiological Responses Effects of Stress on Memory Acute & Chronic Stress Decreases & Increases of Memory Effects of Stress on the Brain Function & Structure Hippocampus Stress Hormones Neuroplasticity
  3. 3. Key Stress Physiologists French physiologist, Claude Bernard Principles of dynamic equilibrium Internal bodily environment External forces External forces (examples) Temperature Oxygen concentration in the air, Expenditure of energy Presence of predators Diseases
  4. 4. Key Stress Physiologists Walter Cannon, Neurologist “Homeostasis“ Stressors-Emotional “Fight or Flight" Response Nor-epinephrine Neurotransmitter
  5. 5. Key Stress Physiologists The Father of Stress Hans Selye is regarded as the “father of stress.” He is also well known for a model of stress called the General Adaptation Syndrome. It has three phases: Alarm: the individual becomes of aware of the stressor Resistance: the individual attempts to fight off and/or adapt to the stressor Exhaustion: the costs of fighting and/or adaptation are so high the individual wears out
  6. 6. Stress Defined No universal definition accepted “Any external stimulus that threatens homeostasis” (Hans Selye) “a perceived threat to homeostasis and as an event or stimulus that causes an often abrupt but always large change in autonomic activity and hormone secretion-particularly cortisol and prolactin” (Wolkowitz & Rothschild, 2003)
  7. 7. Contributing Factors to Stress Stress is a highly individualized experience (Wolkowitz 2003) Not all stressful events are stressful to every person Contributing Factors: Genetic predisposition Developmental stage Gender Perception of the stressor
  8. 8. External and Internal Stressors External stressors: physical conditions (such as pain or hot or cold temperatures) stressful psychological environments (such as poor working conditions or abusive relationships). Internal stressors: physical (infections, inflammation) Psychological (i.e. intense worry about a harmful event that may or may not occur)
  9. 9. Classification of Stress Acute Stress (short term fight or flight) Noise Crowding Imagining a threat or remembering a dangerous event Chronic Stress Financial worries Loneliness Relationship problems Ongoing highly pressured at work.
  10. 10. Brain Structures Affected by Stress
  11. 11. Brain Functions & Stress Brain Controls when & where stress hormones will be released Defines the perception on what is stressful Determined by past experience (injury, abuse, etc.) Past experiences can affect neuroplascitiy
  12. 12. Physiological Responses of Stress Stressor
  13. 13. Physiological Responses of Stress Allostasis When stress persists for too long the protective physiological mechanisms become overburdened, leading to allostatic load (Sterling and Eyer, 1988) Affected by real or imagined event: Varies among individuals (Schulkin et al. 1994) Allostatic Load Causes a wear and tear effect from chronic stressors Cortisol (Glucocorticoid) Negative health effects (Wolkowitz, 2003)
  14. 14. Acute and Chronic Effects from Cortisol (Glucocorticoid) Acute Stress Chronic Stress Metabolism: Stimulation of gluconeogenesis Adult onset diabetes, obesity. Increase heart pressure, heart rate Hypertension, heart disease Sharpening of cognitive skills, memory Damage to memory system Decrease growth functions Stunted growth Decrease brain metabolism Neural degeneration Loss of reproductive function Loss of reproductive function Decrease immune response Decrease immune response
  15. 15. Effects of Stress on Memory Acute: Memory Enhancement Occur in low stress emotional situations Memory Decrease Declarative memory Brain Metabolism Decrease CG’s down regulates brain metabolism Beneficial during energy crisis Long term effect: 1) Lower brain metabolism leads to inability of neurons to survive 2) Resulting in severe neuronal atrophy or death During enhancement of memory Certain types of memory favored (i.e. emotional) Poor encoding Retrieval also affected negatively Chronic: Memory decrease Hippocampal atrophy Neuroplasticity
  16. 16. Acute Stress: Memory Enhancement Humans Animals/Rats Emotional events (stressful-flashbulb Stress enhanced delay and trace eye blink effect) well remembered conditioning (Mc Gaugh and Cahill ) Mc Gaugh and Cahill tested episodic Spatial navigation among adrenalectomized memory of movies or slide shows that have rats with no GC, were found impaired stressful sections “Systemic injection of norepinephrine They found: The amygdala is highly active increases the retention of avoidance response” during emotional portion of the movie and activation correlates with memory retention Further, patients that had amygdala lesions did not show the effect
  17. 17. Acute Stress: Memory Decrease Human Animals/Rats Declarative memory retrieval found Rats: When exposed to a cat had reduced affected in men (and not women) after spatial learning (Mc Gaugh and Cahill ) social stress (Mc Gaugh and Cahill) This was strongly associated with a Gender Differences (Shors, 2001) decrease (both in vitro and in vivo) of LTP in Demonstrated: CA1 1) Dendritic spines sensitive to acute stress 2) Respond in opposite directions to the same stimulus based on gender differences & hormonal changes
  18. 18. Memory Decrease From Acute Stress in Humans Flashbulb Memories are enhanced from that time (Brown & Kulik, 1977) Enhancement of memory attributed rehearsal effect (Winograd & Neisser, 1992) Repeated discussing event in later days Results in distortions of memory (inaccurate recall) Rehearing of inaccurate memory becomes stronger
  19. 19. Memory Decrease From Chronic Stress in Humans Inhibit Laying Down of Memory Biased memory towards threat Experiments: Photographs resulted in viewers focusing on the threat and less memory of other portions (Christian, Loftus, Hoffman & Loftun, 1991) Neurohormonal Modulation of Memory Fight-or-flight: Norepinephrine and epinephrine strengthen laying down of memory-hippocampus Cortisol inhibits laying down of memories
  20. 20. Chronic Stress Effect on Hippocampus Elevated glucocorticoids results: Hippocampus damage (Sapolsky et al., 1990) Impairing Memory & Long Term Potentiation (Luine, Villages, Martinex & McEwen, 1994) New Learning Memory (Arbel, Kadar, Silberman & Levy, 1994) Study: Found that monkey hippocampus sustained glucocorticoid related damage (Sapolsky et al., 1990)
  21. 21. Chronic Stress Effect on Hippocampus, cont’d Neurons Decrease normal branching Results in death of neurons (Magarinos, Verdugo, & McEwen, 1997) Atrophy Decrease in serotonin 5HT receptor binding within hippocampus Associated with atrophy (CA3 Region of hippocampus and memory impairment (McEwen et al., 1997) Brain-Derived Neurotrophic Factor (BDNF) Reduction in BDNF May be related to release of Glucocorticoid (Smith et al., 1995) or Serotonin 5HT receptor stimulation (Vaidya, Marek, Aghajanian & Duman, 1997) Smith (1995) also suggests that decreased levels of BDNF may cause hippocampus atrophy or cell death
  22. 22. Atrophy of Hippocampus Sapolsky (2000) reviewed 3-studies studying severe depression that used MRI technology to image the hippocampus Depression: Found all subjects reported hippocampal atrophy Atrophy did not resolve over time Appeared to be irreversible
  23. 23. Hippocampal Atrophy from Depression Range of Atrophy 8-19% Laterality of Atrophy Trend toward left-sided atrophy>right-sided atrophy Anatomical Specificity Volume loss reported in hippocampus; frontal cortical and cell loss reported Functional Evidence for deficits in explicit memory Consequences When Atrophy Occurs No evidence for deficits in explicit memory Likely Mechanisms Cell loss and inhibition of neurogenesis Undergo Atrophy Role for Glucocorticoids Indirectly implicated Sapolsky (2000)
  24. 24. Atrophy of Hippocampus from PTSD PTSD (Post-traumatic stress disorder): Flashbulb memory of some images of the traumatic and unusually fragmented episodic memory of the entire event Sapolsky (2000) reviewed 5-studies on PTSD Found all studies that researched changes in the hippocampus in PTSP reported atrophy in that region
  25. 25. Hippocampal Atrophy from PTSD Range of Atrophy 5-26% Laterality of Atrophy Conflicting data Anatomical Specificity Volume loss reported in hippocampus Functional Consequences Strong evidence deficits in explicit memory When Atrophy Occurs Mixed evidence Likely Mechanisms Cell loss and inhibition of neurogenesis Undergo Atrophy Role for Glucocorticoids No role if atrophy preceded trauma: indirectly implicated if atrophy arises from trauma, conflicting evidence if trauma arisis from PTSD Sapolsky (2000)
  26. 26. Atrophy of Hippocampus from Cushing Syndrome Cushing Syndrome: Characterized by hypersecreation of cortisol, resulting in corticotrpin-releasing hormone secreting tumors that result in hypercortisolism Pathologic studies suggest the effect is hippocampus atrophy Studies: Severe atrophy associated with severe hypercortisolism (Sapolsky, 2000)
  27. 27. Hippocampal Atrophy from Cushing Syndrome Range of Atrophy na Laterality of Atrophy None Anatomical Specificity Volume loss reported in hippocampus, caudate, and cortex: ventricles enlarged Functional Consequences Strong evidence deficits in explicit memory When Atrophy Occurs No evidence for atrophy prior to disease onset Likely Mechanisms Tissue compression, regression of dendrites and inhibition of Undergo Atrophy neurogenesis Role for Glucocorticoids Highly likely Sapolsky (2000)
  28. 28. Effect of Cortisol on Memory Randomized, double blind, placebo-controlled study, Newcomer et al., 1999 (N=51) Methodology: Gp-1: High steriod group 160mg/d (dose similar to experiencing major abdominal surgery) Gp-2: Low steriod group 40mg/d (dose similar to experiencing minor procedures such as removal of stitches Gp-3: Pladebo group
  29. 29. Effect on Cortisol on Memory Study Results (Newcomer et al., 1999) 120 Verbal Declarative Memory 100 Performance 80 Gp-1: 160mg/d 60 Gp-2: 40mg/d Gp-3: Placebo 40 20 0 Baseline Day-1 Day-4
  30. 30. Neuroplasticity & Stress Rainnie DG, et al (2004) Stress peptide-inducted behavior syndrome correlated with cellular mechanisms of neural plasticity Cao J, et al (2004) Stress-facilitated Long-Term Depression (LTD) induces output plasticity through synchronized-spikes suggest stress- related plasticity plays a significant role in distribution, integration, and amplification of encoded information to other brain structures under stress Kuipers SD, et al (2004) Confirmed that the damaging effect of stress on cortical activity, on a molecular lever suggest underlying cellular actions of stress in the brain.
  31. 31. Conclusion Physiological responses of stress: Necessary for adaptation Both increases & decreases memory for survival Chronic stress (excessive levels of cortisol): Impair successful adaptation due to glucocorticoid secretion (poor regulation of endocrine response to stress) Inhibits laying down of memory, LTP, & new learning Hippocampal atrophy and death of neurons Neuroplasticity
  32. 32. Implications for Stress Related Effects on Memory Improved Treatment PTSD, depression, etc. Research & Clinical Application Alzheimer’s Disease Dementia IPV Adult Manifestation of Early Childhood Trauma (ECT)