The HPA axis & Memory Function In Humans

Impact of stress on memory 2 principal effects Forget something due to stress e.g. wedding anniversary Vivid memory of an emotional situation e.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 rhythm perspiration

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 attention allowed to an event will depend on the VALENCE of 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, 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 groups Group 1 : Neutral slides through the series Group 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 Months TRAUMA Acute Stress Disorder 1 month3 months Acute PTSD 6 months Chronic PTSD

Memory of an emotional event Focus on Central Details : Memory Bias in ANXIETY Feelings of Lack Of control over « threatening » Situations

Anxiety Symptoms Panic Attacks Generalized Anxiety Disorder

Anxiety & Memory In anxiety, there is an attentional bias for threat Anxious patients (and also PTSD patients) have a tendency To systematically attend to threatening informations and to Avoid 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 AnxiousNon-Anxious Task : Listen to words and write them down later --> 2 types of words : Neutral vs Homophones with threat e.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., groups : Phobics for spiders vs controls Task : Stroop neutral vs emotional words RedBlueYellowJeansHouse Spider GreenBlackPinkCatWeb 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

Immediate vs Delayed Memory of emotional events Study by Cahill et al., 1998: 2 groups of controls Task 1 : 12 slides all neutral Task 2 : 12 slides, those 4 in the middle (5-8) are emotional Slide number Neutral group Emotional Group Recall : performed 2 weeks after encoding

Biological Explanation Release of Adrenaline Cardiac Rhythm Perspiration Tremors 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 number Propanolol group Placebo 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 of rape had significantly lower cortisol levels in 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 survivors Suffering from PTSD also present The hormonal dysfunction of PTSD Possibility of a Genetic component

Impact of STRESS on Memory

HORMONES CRF ACTH GCs Stress ResponseRecovery GLUCOCORTICOIDS

Circadian Rhythm 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 Memory Performance Circulating Levels of GCs Same Inverted-U Shape between GCs and LTP In rats

Adrenal Steroid Receptors : AFFINITY Levels of circulating glucocorticoids Type I receptor activation (6 fold higher affinity) Type II receptor activation (low affinity for GC) BASAL Levels of GC STRESS Levels of GC Localization of Steroid Receptors in the Brain

Mechanism? Receptors : 2 Types  Different Affinity  Different Distribution in the Brain Type I : High Affinity Type II: Low Affinity AFFINITY Hippocampus : Frontal : DISTRIBUTION

Circulating Concentrations GCs Memory Performance Important implications For the effects of Glucocorticoids on Memory function

Memory Performance CIrculating Levels of Glucocorticoids facilitationinhibition Activation Type I Activation Type II Young AFFINITY & HIPPOCAMPUS Decrease in Cortisol Replacement of Cortisol Hormone Replacement Protocol

Young 8% MR GR SST Mnesic Performance Circulating Glucocorticoid Levels facilitationinhibition Activation Type I Activation Type II Moderate Cortisol - Young

This is not the end of the story….. …There are also GC receptors in the frontal lobe

Type I Type II Anatomical Distribution of Type I and Type II Type I : Tonic Influence on HPA Acute Increase Of 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)

Cortisol Cortisol (µg/dl) Placebo 40µg/kg/h 300µg/kg/h 600µg/kg/h Time **

RelatedUnrelated Placebo 40µg/kg/h 300µg/kg/h 600µg/kg/h Word Pair Association Correct Recall Declarative Memory Results :

Effets of Stress Hormones on Human Memory …. A lot of methodological implications related to the :  Inverted-U shape curve  Receptors in Frontal Lobe

Circulating Concentrations GCs Memory Performance Stress/GCs

Circulating Concentrations GCs Memory Performance GCs AM Levels GCs PM Levels Fehm-Wolfsdorf et al., 1993: Placebo : Memory > Placebo : Memory <

Circulating Concentrations GCs Memory Performance AM PM Stress/GCs Fehm-Wolfsdorf et al., 1993: Lupien et al., 2002

Circulating Concentrations GCs Memory Performance -Young -Normal Adults -PTSD -Burn-Out -30% Elderlies -Alzheimer -Depressed

Circulating Concentrations GCs Memory Performance -Young -Normal Adults -PTSD -Burn-Out -30% Elderlies -Alzheimer -Depressed 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