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