Reconsolidation of emotional memories - a psychobiological investigation with functional magnetic resonance imaging
Final Report Abstract
1. How does emotion modulate learning and memory in humans? Our memories are not veridical representations of our experiences; rather our experiences are transformed into memory representations. Emotion influences this process by acting on all memory stages (encoding, consolidation, retrieval, and reconsolidation). Behaviorally, real-life and laboratory studies have shown that humans remember emotional events particularly well. Thereby emotion not only enhances memory accuracy, but affects the subjective sense of recollection even more: Emotion intensifies the subjective vividness of the memory, the sense of reliving the event, and confidence in the accuracy of the memory. Surprisingly, however, the enhanced recollective experience for emotional events is often not accompanied by enhanced memory for all elements of an experience . One possibility explaining this discrepancy is that emotion increases the subjective recollective experience via enhancing memory for a few relevant details, such as the weapon used in a crime, at the expense of less relevant information, such as the perpetrator’s face. Indeed, novel behavioral paradigms and a study on 9/11 I showed that emotion selectively affects what is bound to a memory representation, i.e. emotion strengthens the subjective recollective experience and simultaneously enhances knowledge for when and where an event happened, but decreases knowledge for less relevant information. To get at the neurobiological mechanism of emotion’s modulation on the subjective recollective experience, I carried out a pharmacological and a neuro-imaging study. Using a double-blind, placebo controlled, within-subject design, I showed that reducing arousal at encoding through oral intake of 80-mg of the beta-adrenergic receptor antagonist propranolol decreases the subjective sense of recollection for both negative and neutral stimuli 24 hours later. In contrast, administration of propranolol before memory retrieval did not alter the subjective sense of recollection. These results suggest that the neurohormonal changes underlying increased arousal at the time of memory formation, rather than the time of memory retrieval, modulate the subjective sense of recollection. Furthermore, in a recent study published in Nature Neuroscience, we showed that increased levels of arousal, induced through emotional stimuli, prospectively enhanced memory formation for temporally distant neutral stimuli (in particular increased the subjective recollection). Indeed multiple measures of emotion-related brain activity showed evidence of persistence into subsequent periods when neutral stimuli were encountered. As such, e.g. low-frequency multivoxel amygdala connectivity and amygdala-anterior hippocampus connectivity, as well as transient, stimulus-evoked activity predictive of trial-by-trial memory formation showed evidence of persistence from emotional encoding into subsequent neutral encoding. These results indicate that neural measures of an emotional experience persist and influence how new, unrelated, information is encoded and recollected. 2. What is the role of stress hormones (cortisol) and their receptors in emotional learning and memory? Upon exposure to an emotional event, the body rapidly releases the stress hormones epinephrine and norepinephrine, and more slowly the hormone cortisol. Abundant scientific evidence suggest that these hormones modulate memory for emotional events. Yet their exact neurobiological mechanism remains to be elucidated. Evidence, predominantly from animal studies suggests that these hormones influence memory by acting in concert with amygdala and hippocampal activation. Thereby their action on memory can be different, depending on the memory stage (e.g. high cortisol levels induced by a stressor are thought to enhance encoding/consolidation, but impair retrieval). Understanding and manipulating the hormonal processes at the key stages of memory offers the possibility to change the retention of emotional experiences, and ultimately behavior. As such, I have undertaken stress-induction and pharmacological studies to understand how stress hormones, in particular cortisol, affect each memory stage. During my post doc, I showed that lowering cortisol levels pharmacologically impaired memory retrieval, specifically the recall of an emotional experience. To better understand cortisol’s effects on memory retrieval, I was able to nicely delineate the role of the two major cortisol receptors during retrieval: pharmacological blockade of the mineralocorticoid receptor impaired retrieval, while blockade of the glucocorticoid receptor enhanced retrieval.
Publications
- Suppressing the morning rise in cortisol impairs free recall (2010). Learning and Memory 17, 186-190
Rimmele U., Meier, F., Lange, T., Born, J.
- (2011). Emotion enhances the subjective feeling of remembering despite lower accuracy for contextual details. Emotion, 11(3), 553-62
Rimmele U., Davachi L., Petrov R., Dougal S., Phelps E.A.
- (2012). Memory for time and place contributes to enhanced confidence for memory of emotional events. Emotion 12(4): 834-46
Rimmele U., Davachi L., Phelps E.A.
- (2013). Blocking mineralocorticoid receptors impairs, blocking glucocorticoid receptors enhances memory retrieval in humans. Neuropsychopharmacology 38(5): 884-94
Rimmele U., Besedovsky L., Lange T., Born J.
(See online at https://doi.org/10.1038/npp.2012.254) - (2015). Emotional memory can be persistently weakened by suppressing cortisol at retrieval. Neurobiology of Learning and Memory 119: 102- 107
Rimmele U., Besedovsky L., Lange T., Born J.
(See online at https://doi.org/10.1016/j.nlm.2015.01.010) - (2016). Beta-adrenergic blockade at memory encoding, but not retrieval, decreases the subjective sense of recollection. Journal of Cognitive Neuroscience 28(6): 895-907
Rimmele U., Lackovic S., Russell T., Leventhal B., Phelps E.A.
(See online at https://doi.org/10.1162/jocn_a_00941) - (2017). Emotional brain states persist and enhance future memory formation. Nature Neuroscience 20 (2): 271- 278
Tambini, A., Rimmele U., Phelps E.A., Davachi L.
(See online at https://doi.org/10.1038/nn.4468)
