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The HPA axis & Memory FunctionIn Humans
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
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
Difference between STRESS and EMOTION
Differences :
--> Stress always causes an emotion--> Emotion is not always stressful
Laboratory :
--> Emotion : Images, words, etc.--> Stress : public speaking
Impact of EMOTION on Memory
MEMORY is a processus that develops in time
ENCODING
-Vigilance-Attention
consolidation
-Attention : Permits elaboration…more elaborate…better recalled
RECALL
Attention, Emotion and Memory....
The amount of attentionallowed to an event willdepend on the VALENCEof this event
An example…..
A question …..
--> Which one would you remember best?
--> the traumatic ones.
--> High Valence: Increased Attention
--> Better encoding …
--> Better encoding… Better recall later
A demonstration….
The ‘ Flashbulb Memory ’ Phenomenon
… September 26, 1997
... A certain date
Emotion Attention
Attention = Elaboration
Explication
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’
Weapon Focus Phenomenon
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
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)
Acute Stress Disorder vs Post-Traumatic Stress Disorder
MonthsTRAUMA
Acute StressDisorder
1 month 3 months
Acute PTSD
6 months
Chronic PTSD
Memory of an emotional event
Focus on Central Details : Memory Bias in ANXIETY
Feelings of LackOf control over« threatening »Situations
Anxiety Symptoms
PanicAttacks
GeneralizedAnxiety Disorder
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
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
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
Second particularity :
-Immediate vs Delayed memory
Emotional Events : --> Immediate Recall : Poor--> 2 weeks after : Excellent
Memory of an emotional event
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
Biological Explanation
Release ofAdrenaline
Cardiac RhythmPerspirationTremors
Consciousness of state :
Memory
Memory of an emotional event
Implication :« False-Feedback »
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
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
Hormonal dysfunctions in PTSD
Other hormonal dysfunction in relation to trauma
Cortisol levels in PTSD patients :
--> DECREASED basal cortisol levels
--> ENHANCED negative feedback inhibition
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
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
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
Impact of STRESS on Memory
Impact of STRESS on Memory
HORMONES
CRF
ACTH
GCs
+
+
-
-
Stress Response Recovery
GLUCOCORTICOIDS
Circadian Rhythm
8 12 16 20 24 4 8
Krieger, 1978
GCs
Time
HORMONES
CRF
ACTH
GCs
Stress Response
+
+
-
-GC Receptors -Type I : High Affinity -Type II : Low Affinity
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
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
Mechanism?Receptors : 2 Types
Different Affinity Different Distribution in the Brain
Type I : High AffinityType II: Low Affinity
AFFINITY
Hippocampus : Frontal :
DISTRIBUTION
Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
Important implicationsFor the effects ofGlucocorticoids on Memory function
MemoryPerformance
CIrculating Levels of Glucocorticoids
facilitation inhibition
ActivationType I
ActivationType II
Young
AFFINITY & HIPPOCAMPUS
Decrease in Cortisol
Replacement of Cortisol
HormoneReplacementProtocol
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
This is not the end of the story…..
…There are also GC receptors in the frontal lobe
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
Population : Young
Task : Working vs Declarative Memory
Drugs : Placebo vs 60 vs 300 vs 600 mcg/kg/h hydrocortisone (infusion)
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
**
** ****** **
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 :
Effets of Stress Hormones on Human Memory
…. A lot of methodological implications related to the :
Inverted-U shape curveReceptors in Frontal Lobe
Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
Stress/GCs
Stress/GCs
Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
GCs AM Levels
GCs PM Levels
Fehm-Wolfsdorf et al., 1993:
Placebo : Memory >
Placebo : Memory <
Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
AM
PM
Stress/GCsStress/GCs
Fehm-Wolfsdorf et al., 1993:Lupien et al., 2002
Circulating Concentrations GCs
Mem
ory
Perf
orm
an
ce
-Young-Normal Adults
-PTSD-Burn-Out
-30% Elderlies-Alzheimer-Depressed
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
Conclusion :
--> The impact of stress hormones (glucocorticoids) on memory function are RELATIVE, I.e. They depend on
--> Time of day--> Population--> Dose