Impact of a reminder/extinction procedure on threat-conditioned pupil size and skin conductance responses.

Josua Zimmermann,Dominik R Bach

doi:10.1101/lm.050211.119

Abstract

A reminder can render consolidated memory labile and susceptible to amnesic agents during a reconsolidation window. For the case of threat memory (also termed fear memory), it has been suggested that extinction training during this reconsolidation window has the same disruptive impact. This procedure could provide a powerful therapeutic principle for treatment of unwanted aversive memories. However, human research yielded contradictory results. Notably, all published positive replications quantified threat memory by conditioned skin conductance responses (SCR). Yet, other studies measuring SCR and/or fear-potentiated startle failed to observe an effect of a reminder/extinction procedure on the return of fear. Here we sought to shed light on this discrepancy by using a different autonomic response, namely, conditioned pupil dilation, in addition to SCR, in a replication of the original human study. N = 71 humans underwent a 3-d threat conditioning, reminder/extinction, and reinstatement, procedure with 2 CS+, of which one was reminded. Participants successfully learned the threat association on day 1, extinguished conditioned responding on day 2, and showed reinstatement on day 3. However, there was no difference in conditioned responding between the reminded and the nonreminded CS, neither in pupil size nor SCR. Thus, we found no evidence that a reminder trial before extinction prevents the return of threat-conditioned responding.

Highlights

According to a dynamic memory view, consolidated memory traces are malleable, rendered labile by retrieval or reactivation (Nader 2015)
We assessed the efficacy of a reminder/extinction procedure to prevent return of fear in humans, by replicating Schiller et al (2010) with pupil size response (PSR) as an additional index of threat conditioning
We recruited a sample size sufficient to detect an at least 50% reduction of fear memory with 85% power and included overall N = 66 (PSR) and N = 68 (SCR) participants

Summary

Introduction

According to a dynamic memory view, consolidated memory traces are malleable, rendered labile by retrieval or reactivation (Nader 2015). Reconsolidation blockade could provide a potentially powerful way of treating clinical conditions that involve maladaptive aversive memory This has motivated a search for drugs (Debiec and Ledoux 2004; Brunet et al 2008; Kindt et al 2009) or behavioral interference manipulations (Monfils et al 2009; Schiller et al 2010; Schiller and Phelps 2011) that are applicable in humans and can disrupt threat memory during the reconsolidation window. This lack of reinstatement was stable over a year and was specific to the reminded cue (Schiller et al 2010) This may suggest that extinction training during the reconsolidation period overwrites the original fear memory, in contrast to extinction training outside this time window. We recruited a sample that provided 85% power to detect an at least 50% absolute reduction of fear retention, corresponding to the ∼60% reduction found in Schiller et al (2010)

Methods

Results

Conclusion