The HPA axis & Memory Function In Humans

1. The HPA axis & Memory Function In Humans Meeting Accident

2. 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

3. 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

4. Difference between STRESS and EMOTION Differences : --> Stress always causes an emotion --> Emotion is not always stressful Laboratory : --> Emotion : Images, words, etc. --> Stress : public speaking

5. Impact of EMOTION on Memory

6. MEMORY is a processus that develops in time -Vigilance -Attention consolidation RECALL ENCODING -Attention : Permits elaboration …more elaborate…better recalled

7. Attention, Emotion and Memory.... The amount of attention allowed to an event will depend on the VALENCE of this event An example…..

13. A question ….. --> Which one would you remember best? --> the traumatic ones. --> High Valence: Increased Attention --> Better encoding … --> Better encoding… Better recall later A demonstration….

14. The ‘ Flashbulb Memory ’ Phenomenon … September 26, 1997 ... A certain date Explication Emotion Attention Attention = Elaboration

15. Memory of an emotional event First particularity: -Memory for details vs periphery Study of trauma victims --> Excellent memory of traumatic event --> Poor recall of surrounding events ‘Weapon Focus Phenomenon’

16. Weapon Focus Phenomenon

17. 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

18. 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)

19. Acute Stress Disorder vs Post-Traumatic Stress Disorder Acute PTSD Acute Stress Disorder Chronic PTSD Months 1 month 3 months 6 months TRAUMA

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

21. Anxiety Symptoms Panic Attacks Generalized Anxiety Disorder

22. 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

23. 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 threat e.g. Die vs Dye --> Results : Anxious patients remember all the negative homophones Conclusion : Memory bias for threatening information

24. Anxiety & Memory Study #2 : Eysenck et al., 1993 2 groups : Phobics for spiders vs controls Task : Stroop neutral vs emotional words RedBlue Yellow JeansHouseSpider GreenBlackPinkCatWebDog Results : Phobics have longer Reaction times to name the color of phobic words Conclusion : Attentional bias against threatening information

25. Memory of an emotional event Second particularity : -Immediate vs Delayed memory Emotional Events : --> Immediate Recall : Poor --> 2 weeks after : Excellent

26. 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 Recall : performed 2 weeks after encoding Emotional Group Neutral group Slide number 1-4 5-8 9-12

27. Memory of an emotional event Biological Explanation Release of Adrenaline Cardiac Rhythm Perspiration Tremors Consciousness of state : Implication : « False-Feedback » Memory

28. 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 Results : Placebo Group Propanolol group Slide number 1-4 5-8 9-12 Conclusion : if you block adrenaline secretion, you block the enhancing effects of emotion on memory

29. 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

30. Hormonal dysfunctions in PTSD Other hormonal dysfunction in relation to trauma Cortisol levels in PTSD patients : --> DECREASED basal cortisol levels --> ENHANCED negative feedback inhibition

31. 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

32. Hormonal dysfunctions in PTSD 2. Enhanced negative feedback sensitivity - CRF Dex : 0.5 mg (usual dose = 1 or 2 mg) PTSD : Suppress cortisol levels faster and with a stronger response Hyper-suppressor to DEX - ACTH GCs Remember : Depressed are non-suppressor to DEX so this is a major difference between PTSD and depression

33. 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

34. Impact of STRESS on Memory

35. Impact of STRESS on Memory HORMONES GLUCOCORTICOIDS CRF - + Stress Response Recovery ACTH - + GCs

36. Circadian Rhythm Krieger, 1978 GCs 8 12 16 20 24 4 8 Time

37. HORMONES CRF - + ACTH - + GC Receptors -Type I : High Affinity -Type II : Low Affinity GCs Stress Response

38.  Inverted-U shape function between GC levels & cognition Memory Performance Circulating Levels of GCs Animal Studies  Receptor affinity High GCs : -Decreased Memory -Negative Effects on Hippocampus Adrenalectomy : -Decreased Memory -Negative Effects on Hippocampus Same Inverted-U Shape between GCs and LTP In rats

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

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

41. Memory Performance Circulating Concentrations GCs Stress & Memory Inverted-U Shape Important implications For the effects of Glucocorticoids on Memory function

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

43. Moderate Cortisol - Young Mnesic Performance GR SST MR Activation Type I Activation Type II facilitation inhibition Circulating Glucocorticoid Levels Young 8%

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

45. Anatomical Distribution of Type I and Type II Acute Increase Of Cortisol Working Memory Type II Type I Type II Type I : Tonic Influence on HPA Hypothesis : Working memory should be more sensitive than declarative memory to an acute increase in cortisol levels

46. Population : Young Task : Working vs Declarative Memory Drugs : Placebo vs 60 vs 300 vs 600 mcg/kg/h hydrocortisone (infusion)

47. Placebo 40µg/kg/h 300µg/kg/h 600µg/kg/h 845 900 920 1055 1300 1345 Cortisol 100 ** 75 Cortisol (µg/dl) 50 ** ** ** ** ** 25 0 Time

48. Placebo 40µg/kg/h 12 Working Memory 300µg/kg/h & 1500 10 600µg/kg/h & ** Placebo Reaction Times (msec) 8 40µg/kg/h 300µg/kg/h Correct Recall 600µg/kg/h 6 4 500 2 3 4 6 8 9 12 16 Comparison Load 2 0 Related Unrelated Word Pair Association Results : Declarative Memory

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

50. Memory Performance Circulating Concentrations GCs Stress & Memory Inverted-U Shape Stress/GCs Stress/GCs