Stress & Memory

Stress & Memory

James M. DeCarli, PhD Candidate, MPH, MPA, CHES

Departments of Psychology & NeuroscienceUniversity of Southern California

OverviewBackground on Stress

HistoryTypes & ClassificationsPhysiological Responses

Effects of Stress on MemoryAcute & Chronic StressDecreases & Increases of Memory

Effects of Stress on the Brain Function & StructureHippocampusStress HormonesNeuroplasticity

Key Stress Physiologists

French physiologist, Claude BernardPrinciples of dynamic equilibrium

Internal bodily environmentExternal forces

External forces (examples)TemperatureOxygen concentration in the air,Expenditure of energyPresence of predatorsDiseases

Key Stress Physiologists

Walter Cannon, Neurologist “Homeostasis“Stressors-Emotional“Fight or Flight" ResponseNor-epinephrine Neurotransmitter

Key Stress Physiologists

The Father of StressHans 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 stressorResistance: the individual attempts to fight off and/or adapt to the stressorExhaustion: the costs of fighting and/or adaptation are so high the individual wears out

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)

Contributing Factors to Stress

Stress is a highly individualized experience (Wolkowitz 2003)

Not all stressful events are stressful to every personContributing Factors:

Genetic predispositionDevelopmental stageGenderPerception of the stressor

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)

Classification of Stress

Acute Stress (short term fight or flight)Noise CrowdingImagining a threat or remembering a dangerous event

Chronic StressFinancial worriesLonelinessRelationship problemsOngoing highly pressured at work.

Brain Structures Affected by Stress

Brain Functions & Stress

BrainControls when & where stress hormones will be releasedDefines the perception on what is stressful

Determined by past experience (injury, abuse, etc.)Past experiences can affect neuroplascitiy

Physiological Responses of Stress

Stressor

Physiological Responses of Stress

AllostasisWhen 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 LoadCauses a wear and tear effect from chronic stressorsCortisol (Glucocorticoid)

Negative health effects (Wolkowitz, 2003)

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

Effects of Stress on MemoryAcute:

Memory Enhancement Occur in low stress emotional situations

Memory Decrease Declarative memory

Brain Metabolism DecreaseCG’s down regulates brain metabolism

Beneficial during energy crisisLong term effect:

1) Lower brain metabolism leads to inability of neurons to survive2) Resulting in severe neuronal atrophy or death

During enhancement of memoryCertain types of memory favored (i.e. emotional)Poor encoding Retrieval also affected negatively

Chronic:Memory decreaseHippocampal atrophyNeuroplasticity

Acute Stress: Memory EnhancementHumans Animals/Rats

Emotional events (stressful-flashbulb effect) well remembered

Mc Gaugh and Cahill tested episodic memory of movies or slide shows that have stressful sections

They found: The amygdala is highly activeduring emotional portion of the movie and activation correlates with memory retention

Further, patients that had amygdala lesions did not show the effect

Stress enhanced delay and trace eye blink conditioning (Mc Gaugh and Cahill )

Spatial navigation among adrenalectomizedrats with no GC, were found impaired

“Systemic injection of norepinephrineincreases the retention of avoidance response”

Acute Stress: Memory Decrease

Human Animals/RatsDeclarative memory retrieval found affected in men (and not women) after social stress (Mc Gaugh and Cahill)

Gender Differences (Shors, 2001)

Demonstrated:

1) Dendritic spines sensitive to acute stress

2) Respond in opposite directions to the same stimulus based on gender differences & hormonal changes

Rats: When exposed to a cat had reduced spatial learning (Mc Gaugh and Cahill )

This was strongly associated with a decrease (both in vitro and in vivo) of LTP in CA1

Memory Decrease From Acute Stress in Humans

FlashbulbMemories are enhanced from that time (Brown & Kulik, 1977)Enhancement of memory attributed rehearsal effect (Winograd & Neisser, 1992)

Repeated discussing event in later daysResults in distortions of memory (inaccurate recall)Rehearing of inaccurate memory becomes stronger

Memory Decrease From Chronic Stress in Humans

Inhibit Laying Down of MemoryBiased 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 MemoryFight-or-flight: Norepinephrine and epinephrine strengthen laying down of memory-hippocampusCortisol inhibits laying down of memories

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)

Chronic Stress Effect on Hippocampus, cont’d

NeuronsDecrease normal branching Results in death of neurons (Magarinos, Verdugo, & McEwen, 1997)

Atrophy Decrease in serotonin 5HT receptor binding within hippocampusAssociated 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) orSerotonin 5HT receptor stimulation (Vaidya, Marek, Aghajanian & Duman, 1997)Smith (1995) also suggests that decreased levels of BDNF may cause hippocampus atrophy or cell death

Atrophy of Hippocampus

Sapolsky (2000) reviewed 3-studies studying severe depression that used MRI technology to image the hippocampusDepression:

Found all subjects reported hippocampal atrophyAtrophy did not resolve over timeAppeared to be irreversible

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 Consequences

Evidence for deficits in explicit memory

When Atrophy Occurs No evidence for deficits in explicit memory

Likely Mechanisms Undergo Atrophy

Cell loss and inhibition of neurogenesis

Role for Glucocorticoids Indirectly implicated

Sapolsky (2000)

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 PTSDFound all studies that researched changes in the hippocampus in PTSP reported atrophy in that region

Hippocampal Atrophy from PTSDRange 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 Undergo Atrophy

Cell loss and inhibition of neurogenesis

Role for Glucocorticoids No role if atrophy preceded trauma: indirectly implicated if atrophy arises from trauma, conflicting evidence if trauma arisisfrom PTSD

Sapolsky (2000)

Atrophy of Hippocampus from Cushing Syndrome

Cushing Syndrome: Characterized by hypersecreation of cortisol, resulting in corticotrpin-releasing hormone secreting tumors that result in hypercortisolismPathologic studies suggest the effect is hippocampus atrophy Studies: Severe atrophy associated with severe hypercortisolism (Sapolsky, 2000)

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 Undergo Atrophy

Tissue compression, regression of dendrites and inhibition of neurogenesis

Role for Glucocorticoids Highly likely

Sapolsky (2000)

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 group40mg/d (dose similar to experiencing minor procedures such as removal of stitches

Gp-3: Pladebo group

Effect on Cortisol on Memory

Study Results (Newcomer et al., 1999)

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Baseline Day-1 Day-4

Verb

al D

ecla

rativ

e M

emor

y Pe

rform

ance Gp-1: 160mg/d

Gp-2: 40mg/dGp-3: Placebo

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.

Conclusion

Physiological responses of stress:Necessary for adaptationBoth 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 learningHippocampal atrophy and death of neuronsNeuroplasticity

Implications for Stress Related Effects on Memory

Improved TreatmentPTSD, depression, etc.

Research & Clinical ApplicationAlzheimer’s DiseaseDementiaIPVAdult Manifestation of Early Childhood Trauma (ECT)