Behavioral Disruption of Memory Reconsolidation: From Bench to Bedside and Back Again

Drexler 2018

Shira Meir Drexler and Oliver T. Wolf

During the postretrieval reconsolidation “window”, memories can be disrupted, strengthened, or updated using various pharmacological and behavioral manipulations. Behavioral manipulations are more ecologically valid, thus allowing better understating of memory modification under natural conditions, but they can also be less potent compared to pharmacological interventions. In this review we present the current human and animal literature, aiming to understand the modulatory factors (i.e., task relevance, complexity, intensity) that promote reconsolidation disruption in purely behavioral means. The reviewed studies have suggested that both very simple tasks and more complex learning paradigms can be used to disrupt or update memory reconsolidation, even of stronger emotional memories. Stress exposure is a possible interference task, yet the conflicting results leave many open questions regarding its required timing and intensity. Going from bench to bedside and back again, we point to the need for more research in clinical populations to establish the therapeutic potential of reconsolidation-based treatments. Several findings from outside the laboratory offer promising leads for future research.

The Amygdala, Fear and Reconsolidation Neural and Behavioral Effects of Retrieval-Extinction in Fear Conditioning and Spider Phobia

Mappe: skandinaviske/2017 b

JOHANNES BJÖRKSTRAND Upsala University, Swiden

The amygdala is crucially involved in the acquisition and retention of fear memories. Experimental research on fear conditioning has shown that memory retrieval shortly followed by pharmacological manipulations or extinction, thereby interfering with memory reconsolidation, decreases later fear expression. Fear memory reconsolidation depends on synaptic plasticity in the amygdala, which has been demonstrated in rodents using both pharmacological manipulations and retrieval-extinction procedures. The retrieval-extinction procedure decreases fear expression also in humans, but the underlying neural mechanism have not been studied. Interfering with reconsolidation is held to alter the original fear memory representation, resulting in long-term reductions in fear responses, and might therefore be used in the treatment of anxiety disorders, but few studies have directly investigated this question.

The aim of this thesis was to examine the effects of the retrieval-extinction procedure on amygdala activity and behavioral fear expression in humans. The work presented here also investigated whether findings from studies on recent fear memories, established through fear conditioning, extends to naturally occurring long-term phobic fears.

Study I, combining fear conditioning and a retrieval-extinction procedure with functional magnetic resonance imaging (fMRI), demonstrated that memory retrieval shortly followed by extinction reduces later amygdala activity and fear expression in healthy subjects. In Study II, these subjects were re-tested 18 months later. The results showed that the effects on fear expression were still present and that initial amygdala activity predicted long-term fear expression. Using an adapted version of the retrieval-extinction procedure, Study III showed that memory retrieval shortly followed by exposure to spider pictures, attenuates subsequent amygdala activity and increases approach behavior in subjects with life-long fear of spiders. In Study IV, these subjects were re-tested 6 months later, and the results showed that effects on amygdala activity as well as approach behavior were maintained.

In summation, retrieval-extinction leads to long-lasting reductions in amygdala activity and fear expression. These findings are consistent with the hypothesis that retrieval-extinction alters an amygdala dependent fear memory. Retrieval-extinction can also attenuate long-term phobic fears, indicating that this manipulation could be used to enhance exposure-based treatments for anxiety disorders.


Disruption of Reconsolidation Erases a Fear Memory Trace in the Human Amygdala

Mappe: skandinaviske/2012 a

Thomas Agren, Department of Psychology.

Uppsala University, SE-751 42 Uppsala, Sweden.

Memories become labile when recalled. In humans and rodents alike, reactivated fear memories can be attenuated by disrupting reconsolidation with extinction training. Using functional brain imaging, we found that, after a conditioned fear memory was formed, reactivation and reconsolidation left a memory trace in the basolateral amygdala that predicted subsequent fear expression and was tightly coupled to activity in the fear circuit of the brain. In contrast, reactivation followed by disrupted reconsolidation suppressed fear, abolished the memory trace, and attenuated fear-circuit connectivity. Thus, as previously demonstrated in rodents, fear memory suppression resulting from behavioral disruption of reconsolidation is amygdala-dependent also in humans, which supports an evolutionarily conserved memory-update mechanism.


Think twice, it’s all right: Long lasting effects of disrupted reconsolidation on brain and behavior in human long-term fear

Mappe: skandinaviske/2017 a

Johannes Björkstrand a,∗ , Thomas Agren a , Fredrik Åhs  , Andreas Frick, Elna-Marie Larsson , Olof Hjorth, Tomas Furmark, Mats Fredrikson

Department of Psychology, Uppsala University.

Memories can be modified when recalled. Experimental fear conditioning studies support that amygdala-localized fear memories are attenuated when reconsolidation is disrupted through extinction training immediately following memory activation. Recently, using functional brain imaging in individuals with lifelong spider fears, we demonstrated that fear memory activation followed by repeated exposure to feared cues after 10 min, thereby disrupting reconsolidation, attenuated activity in the amygdala during later re-exposure, and also facilitated approach behavior to feared cues. In contrast, repeated exposure 6 h after fear memory activation, allowing for reconsolidation, did not attenuate amygdala activity and resulted in less approach behavior as compared to the group that received disrupted reconsolidation. We here evaluated if these effects are stable after 6 months and found that amygdala activity was further reduced in both groups, with a tendency towards greater reductions in the 10 min than the 6 h group. Hence, disrupted reconsolidation results in long lasting attenuation of amygdala activity. The behavioral effect, with more approach towards previously feared cues, in the 10 min than the 6 h group also persisted. Thus, the brain effect of disrupted reconsolidation is stable over 6 months and the behavioral effect also remained. We therefore conclude that disrupted reconsolidation result in a long-lasting diminished fear memory representation in the amygdala which may have clinical importance.

Memory Reconsolidation Interference as an Emerging Treatment for Emotional Disorders: Strengths, Limitations, Challenges, and Opportunities

Tom Beckers 1 and Merel Kindt 2

Experimental research on emotional memory reconsolidation interference, or the induction of amnesia for previously established emotional memory, has a long tradition, but the potential of that research for the development of novel interventions to treat psychological disorders has been recognized only recently. Here we provide an overview of basic research and clinical studies

on emotional memory reconsolidation interference. We point out specific advantages of interventions based on memory reconsolidation interference over traditional treatment for emotional disorders. We also explain how findings from basic research suggest limitations and challenges to clinical translation that may help to understand why clinical trials have met with mixed success so far and how their success can be increased. In closing, we preview new intervention approaches beyond the induction of amnesia that the phenomenon of memory reconsolidation may afford for alleviating the burden imposed by emotional memories and comment on theoretical controversies regarding the nature of memory reconsolidation.