No persistent attenuation of fear memories in humans: A registered replication of the reactivation-extinction effect

Abstract

It has been proposed that memory retrieval can destabilize consolidated memories, after which they need to be reconsolidated in order to be retained. The presentation of relevant information during memory reconsolidation could then result in the modification of a destabilized memory trace, by allowing the memory trace to be updated before being reconsolidated. In line with this idea, Schiller et al. (2010) have demonstrated that memory retrieval shortly before extinction training can prevent the later recovery of conditioned fear responding that is observed after regular extinction training. Those findings have been the subject of considerable controversy, due in part to theoretical reasons but also due to a number of failures to obtain similar results in conceptual replication attempts. Here, we report the results of a highly powered, direct, independent replication of the critical conditions of Schiller et al. (2010, Experiment 1). Due to misrepresentation of the exclusion criteria in the original Schiller et al. (2010) report, data collection was considerably delayed. When we eventually managed to attain our pre-registered sample size, we found that we could not observe any benefit of reactivation-extinction over regular extinction training in preventing recovery of conditioned fear. The results of the present study, along with the mixed findings in the literature and the misreporting in Schiller et al. (2010), give cause to question whether there is robust evidence that reactivation-extinction prevents the return of fear in humans.

Reply to Beckers, McIntosh and Chambers on the verification of ‘preventing the return of fear using retrieval-extinction in humans’

“…Of this vast literature, the verification report mentioned only a few studies; and the authors' failed replication of retrieval-extinction (Chalkia et al, 2020b) selectively cited 7 successful and 7 failed replications only. Such imbalanced representation of the literature creates a false picture of the actual state of the science of the retrieval-extinction effect in humans.…”

Molecular Mechanisms of Reconsolidation-Dependent Memory Updating

“…The reconsolidation-extinction protocol has been found to promote more permanent extinction in both animal [47,[72][73][74]80,91] and human studies [53], suggesting that it might be used to treat clinical disorders such as PTSD [4]. Unfortunately, this method does not always persistently attenuate memories [46,52,69,77,108,109,115], with remote memories showing particular resistance [47], and even direct replications have failed in some cases (Table 1, [77,107]). In 2010, Schiller and colleagues published a study using the reconsolidation-extinction paradigm in humans to successfully attenuate fear memories [53].…”

“…In 2010, Schiller and colleagues published a study using the reconsolidation-extinction paradigm in humans to successfully attenuate fear memories [53]. In 2020, Chalkia and colleagues published two papers in direct response to the Schiller (2010) paper [52,107] that cast doubt on the effectiveness of reconsolidation-extinction in humans. The first publication reported that, in a direct replication of the original study, the authors were unable to replicate the results [52].…”

“…In 2020, Chalkia and colleagues published two papers in direct response to the Schiller (2010) paper [52,107] that cast doubt on the effectiveness of reconsolidation-extinction in humans. The first publication reported that, in a direct replication of the original study, the authors were unable to replicate the results [52]. For the second publication, Chalkia and colleagues obtained the original datasets from the Schiller (2010) paper to replicate the analyses on the same datasets.…”

“…Much of the subsequent work on reconsolidation has been performed using fear conditioning, but in recent years, this work has been extended to multiple types of memory, including spatial, taste, and human episodic memory paradigms [ 1 , 16 ] (more on paradigms in Section 3 ). These paradigms have been used in many different species, from medaka fish [ 28 ] to honeybees [ 29 , 30 ], nematodes [ 31 ], snails [ 32 ], crabs [ 33 ], and chickens [ 34 ], with most of the work performed in mice [ 2 , 12 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ], humans [ 52 , 53 , 54 , 55 , 56 , 57 , 58 ], and rats [ 6 , 8 , 9 , 13 , 14 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 28 , 59 , 60 , 61 , 62 ,…”