Stress and memory-implications for stress related effects on memory

1. Stress & Memory
James M. DeCarli, PhD Candidate, MPH, MPA, CHES
Departments of Psychology & Neuroscience
University of Southern California

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. 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. Key Stress Physiologists
Walter Cannon, Neurologist
“Homeostasis“
Stressors-Emotional
“Fight or Flight" Response
Nor-epinephrine Neurotransmitter

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. 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. 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. 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. 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. Brain Structures Affected by Stress

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. Physiological Responses of Stress
Stressor

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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)