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The HPA axis & Memory FunctionIn Humans
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Impact of stress on memory
2 principal effects
Forget something due to stresse.g. wedding anniversary
Vivid memory of an emotional situatione.g., car accident
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Differences between STRESS and EMOTION
Similarity
--> Stress : Always cause an emotion--> Emotion : Can cause a stress
In both cases:--> Can identify the source--> Lasts for a brief moment--> Creates physical reactions
- Cardiac rhythmperspiration
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Difference between STRESS and EMOTION
Differences :
--> Stress always causes an emotion--> Emotion is not always stressful
Laboratory :
--> Emotion : Images, words, etc.--> Stress : public speaking
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Impact of EMOTION on Memory
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MEMORY is a processus that develops in time
ENCODING
-Vigilance-Attention
consolidation
-Attention : Permits elaboration…more elaborate…better recalled
RECALL
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Attention, Emotion and Memory....
The amount of attentionallowed to an event willdepend on the VALENCEof this event
An example…..
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A question …..
--> Which one would you remember best?
--> the traumatic ones.
--> High Valence: Increased Attention
--> Better encoding …
--> Better encoding… Better recall later
A demonstration….
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The ‘ Flashbulb Memory ’ Phenomenon
… September 26, 1997
... A certain date
Emotion Attention
Attention = Elaboration
Explication
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Memory of an emotional event
Study of trauma victims
--> Excellent memory of traumatic event--> Poor recall of surrounding events
First particularity:
-Memory for details vs periphery
‘Weapon Focus Phenomenon’
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Weapon Focus Phenomenon
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Memory of an emotional event
Study by Christianson :
-Series of Slides: 2 groupsGroup 1 : Neutral slides through the seriesGroup 2 : One slide depicts a traumatic events
In both series : the background is the same (e.g. bicycle/house)
Results : Group 1 remember more background information than Group 2
--> Trauma : Focussing on central details
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Memory of an emotional event
-Trauma : Can lead to Post-Traumatic Stress disorder
--> Dissociation (might be related to high focus on central)--> Depersonalization (Detachment from self)--> Derealization (Everything seems unfamiliar)--> Flashback (Intrusive Flashbulb memory phenomenon)--> Hyperarousal (Red Flags everywhere)--> Intrusive Symptoms (« Reliving » of the trauma)
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Acute Stress Disorder vs Post-Traumatic Stress Disorder
MonthsTRAUMA
Acute StressDisorder
1 month 3 months
Acute PTSD
6 months
Chronic PTSD
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Memory of an emotional event
Focus on Central Details : Memory Bias in ANXIETY
Feelings of LackOf control over« threatening »Situations
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Anxiety Symptoms
PanicAttacks
GeneralizedAnxiety Disorder
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Anxiety & Memory
In anxiety, there is an attentional bias for threat
Anxious patients (and also PTSD patients) have a tendencyTo systematically attend to threatening informations and toAvoid processing non-threatening information
Problem in SELECTIVE ATTENTION:--> Capacity to discriminate between RELEVANT and IRRELEVANT information
In anxious patients : RELEVANT = THREATENING
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Anxiety & Memory
Study 1 : Eysenck et al., (1987) --> 2 groups
Anxious Non-Anxious
Task : Listen to words and write them down later
--> 2 types of words : Neutral vs Homophones with threate.g. Die vs Dye
--> Results : Anxious patients remember all the negative homophones
Conclusion : Memory bias for threatening information
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Anxiety & Memory
Study #2 : Eysenck et al., 1993
2 groups : Phobics for spiders vs controlsTask : Stroop neutral vs emotional words
Red Blue Yellow Jeans House SpiderGreen Black Pink Cat Web Dog
Results : Phobics have longer Reaction times to name the color of phobic words
Conclusion : Attentional bias against threatening information
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Second particularity :
-Immediate vs Delayed memory
Emotional Events : --> Immediate Recall : Poor--> 2 weeks after : Excellent
Memory of an emotional event
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Memory of an emotional event
Immediate vs Delayed Memory of emotional events
Study by Cahill et al., 1998: 2 groups of controls
Task 1 : 12 slides all neutralTask 2 : 12 slides, those 4 in the middle (5-8) are emotional
Slide number1-4 5-8 9-12
Neutral groupEmotional Group
Recall : performed2 weeks after encoding
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Biological Explanation
Release ofAdrenaline
Cardiac RhythmPerspirationTremors
Consciousness of state :
Memory
Memory of an emotional event
Implication :« False-Feedback »
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Memory of an emotional event
Study #2 Cahill et al., (1998) :
--> 2 Groups : Placebo vs Propanolol (antagonist adrenaline)--> Both groups received the emotional story with 12 slides
Slide number1-4 5-8 9-12
Propanolol groupPlacebo Group
Results :
Conclusion : if you block adrenaline secretion, you block the enhancing effects of emotion on memory
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Memory of an emotional event
Antagonist adrenaline block memory enhancing effects of emotion
Application to traumatic syndrome
--> New York Scientists : Clinical trial in ASD victims
--> Administer propanolol very close to the time of trauma
Rationale : By blocking adrenaline surge induced by trauma (with administration of antagonist adrenaline) one might prevent the induction of the traumatic flashbulb phenomenon
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Hormonal dysfunctions in PTSD
Other hormonal dysfunction in relation to trauma
Cortisol levels in PTSD patients :
--> DECREASED basal cortisol levels
--> ENHANCED negative feedback inhibition
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Hormonal dysfunctions in PTSD
1. Decreased Basal cortisol secretion
Yehuda et al., 1992 : Women with a prior history ofrape had significantly lower cortisol levelsin the immediate aftermath of a rape
Conclusion : First trauma : decreased cortisol levels These decreased cortisol levels prevent further stress-related « normal » cortisol response
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Hormonal dysfunctions in PTSD
2. Enhanced negative feedback sensitivity
CRF
ACTH
GCs
-
-Dex : 0.5 mg(usual dose = 1 or 2 mg)
PTSD : Suppress cortisol levels faster and with a stronger response
Hyper-suppressor to DEX
Remember : Depressed are non-suppressor to DEX so this is a major difference between PTSD and depression
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Hormonal dysfunctions in PTSD
Yehuda 1999 : Personal communication
The children of Holocaust survivorsSuffering from PTSD also presentThe hormonal dysfunction of PTSD
Possibility of aGenetic component
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Impact of STRESS on Memory
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Impact of STRESS on Memory
HORMONES
CRF
ACTH
GCs
+
+
-
-
Stress Response Recovery
GLUCOCORTICOIDS
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Circadian Rhythm
8 12 16 20 24 4 8
Krieger, 1978
GCs
Time
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HORMONES
CRF
ACTH
GCs
Stress Response
+
+
-
-GC Receptors -Type I : High Affinity -Type II : Low Affinity
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Animal Studies Receptor affinity
High GCs : -Decreased Memory -Negative Effects on Hippocampus
Adrenalectomy : -Decreased Memory -Negative Effects on Hippocampus
Inverted-U shape function between GC levels & cognition
MemoryPerformance
Circulating Levels of GCs
Same Inverted-UShape between GCs and LTPIn rats
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Adrenal Steroid Receptors : AFFINITY
Lev
els
of c
ircu
lati
ng g
luco
cort
icoi
ds
Type I receptor activation(6 fold higher affinity)
Type II receptor activation(low affinity for GC)
BASALLevels of GC
STRESSLevels of GC
Localization of Steroid Receptors in the Brain
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Mechanism?Receptors : 2 Types
Different Affinity Different Distribution in the Brain
Type I : High AffinityType II: Low Affinity
AFFINITY
Hippocampus : Frontal :
DISTRIBUTION
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
Important implicationsFor the effects ofGlucocorticoids on Memory function
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MemoryPerformance
CIrculating Levels of Glucocorticoids
facilitation inhibition
ActivationType I
ActivationType II
Young
AFFINITY & HIPPOCAMPUS
Decrease in Cortisol
Replacement of Cortisol
HormoneReplacementProtocol
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Metyrapone
1 2 3 Delayed50
60
70
80
90
100PlaceboMetyrapone
**
Trial
Hydrocortisone
1 2 3 Delayed50
60
70
80
90
100PlaceboHydrocortisone
Trial
Young
8%
MRMRGR SSTGR SST
Mnesic Performance
Circulating Glucocorticoid Levels
facilitation inhibition
ActivationType I
ActivationType II
Moderate Cortisol - Young
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This is not the end of the story…..
…There are also GC receptors in the frontal lobe
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Type IType II
Type II
Anatomical Distribution of Type I and Type II
Type I : TonicInfluence on HPA
Acute IncreaseOf Cortisol
Working Memory
Hypothesis : Working memory should be more sensitive than declarative memory to an acute increase in cortisol levels
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Population : Young
Task : Working vs Declarative Memory
Drugs : Placebo vs 60 vs 300 vs 600 mcg/kg/h hydrocortisone (infusion)
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CortisolCortisolC
ort
isol (µ
g/d
l)
Placebo40µg/kg/h300µg/kg/h600µg/kg/h
845 900 920 1055 1300 13450
25
50
75
100
Time
**
** ****** **
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2 3 4 6 8 9 12 16
Comparison Load
Working Memory
Placebo40µg/kg/h300µg/kg/h600µg/kg/h
**&
&
ReactionReactionTimes (msec)Times (msec)
500500
15001500
Related Unrelated0
2
4
6
8
10
12
Placebo40µg/kg/h300µg/kg/h600µg/kg/h
Word Pair Association
Corr
ect
Reca
ll
Declarative Memory
Results :
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Effets of Stress Hormones on Human Memory
…. A lot of methodological implications related to the :
Inverted-U shape curveReceptors in Frontal Lobe
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
Stress/GCs
Stress/GCs
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
GCs AM Levels
GCs PM Levels
Fehm-Wolfsdorf et al., 1993:
Placebo : Memory >
Placebo : Memory <
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
AM
PM
Stress/GCsStress/GCs
Fehm-Wolfsdorf et al., 1993:Lupien et al., 2002
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
-Young-Normal Adults
-PTSD-Burn-Out
-30% Elderlies-Alzheimer-Depressed
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Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
-Young-Normal Adults
-PTSD-Burn-Out
-30% Elderlies-Alzheimer-Depressed
Stress/GCs
Stress/GCs
Stress/GCs
Lupien & McEwen, 1997
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Conclusion :
--> The impact of stress hormones (glucocorticoids) on memory function are RELATIVE, I.e. They depend on
--> Time of day--> Population--> Dose