Harnessing reconsolidation to weaken fear and appetitive memories: A meta-analysis of post-retrieval extinction effects.

Abstract

A new understanding of the mechanisms of memory retrieval and reconsolidation holds the potential for improving exposure-based treatments. Basic research indicates that following fear extinction, safety and fear memories may compete, raising the possibility of return of fear. One possible solution is to modify original fear memories through reconsolidation interference, reducing the likelihood of return of fear. Post-retrieval extinction is a behavioral method of reconsolidation interference that has been explored in the context of conditioned fear and appetitive memory paradigms. This meta-analysis examines the magnitude of post-retrieval extinction effects and potential moderators of these effects. A PubMed and PsycINFO search was conducted through June 2014. Sixty-three comparisons examining post-retrieval extinction for preventing the return of fear or appetitive responses in animals or humans met inclusion criteria. Post-retrieval extinction demonstrated a significant, small-to-moderate effect (g = .40) for further reducing the return of fear in humans and a significant, large effect (g = 0.89) for preventing the return of appetitive responses in animals relative to standard extinction. For fear outcomes in animals, effects were small (g = 0.21) and non-significant, but moderated by the number of animals housed together and the duration of time between post-retrieval extinction/extinction and test. Across paradigms, these findings support the efficacy of this pre-clinical strategy for preventing the return of conditioned fear and appetitive responses. Overall, findings to date support the continued translation of post-retrieval extinction research to human and clinical applications, with particular application to the treatment of anxiety, traumatic stress, and substance use disorders.

Extinction after fear memory reactivation fails to eliminate renewal in rats

“…A recent meta-analysis of these and similar studies found that the effects of postretrieval extinction on relapse in animals are typically small and often nonsignificant (Kredlow et al, 2016), which is in line with the current data. That said, in cases where postretrieval extinction was successful, Kredlow and colleagues (2016) found housing conditions and the timing of retention testing to be important factors in the effect. Specifically, the authors found that housing conditions were a significant moderator of postretrieval extinction, such that group housing appeared to reduce the efficacy of postretrieval extinction.…”

“…After conditioning, encountering fear conditioning-related stimuli (the CS, US, and/or conditioned context) can trigger the previously consolidated conditioned memory to enter a labile state that requires reconsolidation (Auber et al, 2013; Clem & Schiller, 2016; Kredlow et al, 2016; Schiller & Phelps, 2011). Behavioral, pharmacological, or neural manipulations during this postretrieval period allows for modification of the fear memory, including weakening or potentially erasing the memory (Auber et al, 2013; Giustino et al, 2016; Kindt et al, 2009; Kindt & van Emmerik, 2016; Lattal & Wood, 2013; Meir Drexler & Wolf, 2016b; Monfils et al, 2009; Nader, 2003, 2015; Nader et al, 2000; Quirk et al, 2010; Schiller et al, 2010; Schwabe et al, 2014; Soeter & Kindt, 2011).…”

“…The possibility that fear memories can be erased has generated enormous excitement in the clinical community (Careaga et al, 2016; Kroes et al, 2016; Post & Kegan, 2017; Quirk et al, 2010; Smith et al, 2017), but the efficacy of “reconsolidation update” procedures in preventing fear relapse is mixed (Auber et al, 2013; Clem & Schiller, 2016; Kredlow et al, 2016; Schiller & Phelps, 2011). A critical variable that has not yet been fully explored might be the procedure used to reactivate the fear memory prior to extinction.…”

New Learning and Unlearning: Strangers or Accomplices in Threat Memory Attenuation?

“…Extinction paradigms leading to persistent threat memory attenuation therefore present an interesting test case for biochemical signatures of new learning and unlearning, since they can presumably engage either extinction or reconsolidation, but not both. For example, in retrieval-extinction the introduction of an isolated CS trial shortly before extinction prevents the subsequent reemergence of threat memory during spontaneous recovery, renewal and reinstatement tests in both rodents and humans [21, 50, 71–80]; although for unknown reasons some studies have failed to replicate these effects (for in-depth reviews see [16, 81, 82]). Reports have favored the interpretation that the initial CS trial destabilizes threat memory and initiates a time-limited lability window during which extinction training can either interfere with memory restabilization or supply new safety-related information that can be integrated into the memory during its reconsolidation.…”

Persistence and plasticity in the human memory system: An empirical investigation of the overwriting hypothesis

“…Seeking to capitalise on this, a number of studies have examined whether performing extinction trials within the putative 'reconsolidation window' might be more e ective at eliminating fear responses than standard extinction protocols (for review see Auber, Tedesco, Jones, Monfils, & Chiamulera, 2013;Kredlow, Unger, & Otto, 2015). The logic here is that reactivation of a memory trace opens a time-dependent window during which that trace can be modified.…”