Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement

Mappe: Authors/D.Schiller/ 2013 a

Daniela Schiller a,1 , Jonathan W. Kanen b , Joseph E. LeDoux c,d,1 , Marie-H. Monfils e , and Elizabeth A. Phelps

Controlling learned defensive responses through extinction does not alter the threat memory itself, but rather regulates its expression via inhibitory influence of the prefrontal cortex (PFC) over amygdala. Individual differences in amygdala–PFC circuitry function have been linked to trait anxiety and posttraumatic stress disorder. This finding suggests that exposure-based techniques may actually be least effective in those who suffer from anxiety disorders. A theoretical advantage of techniques influencing reconsolidation of threat memories is that the threat representation is altered, potentially diminishing reliance on this PFC circuitry, resulting in a more persistent reduction of defensive reactions. We hypothesized that timing extinction to coincide with threat memory reconsolidation would prevent the return of defensive reactions and diminish PFC involvement. Two conditioned stimuli (CS) were paired with shock and the third was not. A day later, one stimulus (reminded CS+) but not the other (nonreminded CS+) was presented 10 min before extinction to reactivate the threat memory, followed by extinction training for all CSs. The recovery of the threat memory was tested 24 h later. Extinction of the non-reminded CS+ (i.e., standard extinction) engaged the PFC, as previously shown, but extinction of the reminded CS+ (i.e., extinction during reconsolidation) did not. Moreover, only the nonreminded CS+ memory recovered on day 3. These results suggest that extinction during reconsolidation prevents the return of defensive reactions and diminishes PFC involvement. Reducing the necessity of the PFC–amygdala circuitry to control defensive reactions may help overcome a primary obstacle in the long-term efficacy of current treatments for anxiety disorders.

 

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.

PTSD: Extinction, Reconsolidation, and the Visual-Kinesthetic Dissociation Protocol

Mappe: teorier-protokolor/NLP/2012 a

Richard M. Gray 1 and Richard F. Liotta 1

Traumatology 18(2) 3–16 2012

Abstract Every year thousands of returning military, state, and local police officers and civilians of every description suffer from the intrusive symptoms of posttraumatic stress disorder (PTSD). Current treatments rooted largely in extinction protocols require extensive commitments of time and money and are often ineffective. This study reviews several theories of PTSD and two important mechanisms that explain when treatment does and doesn’t work: extinction and reconsolidation. It then reviews the research about and suggests an explanatory mechanism for the visual-kinesthetic dissociation protocol (V/ KD), also known as the rewind technique. The technique is notable for its lack of discomfort to the client, the possibility of being executed as a content-free intervention, its speed of operation, and its long-term, if largely anecdotal, efficacy. A case study, specific diagnostics for extinction, and reconsolidative mechanisms and suggestions for future research are pro

Reconsolidation of Human Memory: Brain Mechanisms and Clinical Relevance

Mappe: authors/Karim Nader 2014 a

Lars Schwabe, Karim Nader, and Jens C. Pruessner

The processes of memory formation and storage are complex and highly dynamic. Once memories are consolidated, they are not necessarily fixed but can be changed long after storage. In particular, seemingly stable memories may re-enter an unstable state when they are retrieved, from which they must be re-stabilized during a process known as reconsolidation. During reconsolidation, memories are susceptible to modifications again, thus providing an opportunity to update seemingly stable memories. While initial demonstrations of memory reconsolidation came mainly from animal studies, evidence for reconsolidation in humans is now accumulating as well. Here, we review recent advances in our understanding of human memory reconsolidation. After a summary of findings on the reconsolidation of human fear and episodic memory, we focus particularly on recent neuroimaging data that provide first insights into how reconsolidation processes are implemented in the human brain. Finally, we discuss the implications of memory modifications during reconsolidation for the treatment of mental disorders such as posttraumatic stress disorder and drug addiction.