Reactivation-Dependent Amnesia for Contextual Fear Memories: Evidence for Publication Bias.

Natalie Schroyens,Eric L Sigwald,Tom Beckers,Laura Luyten,Wim Van Den Noortgate

doi:10.1523/eneuro.0108-20.2020

Abstract

Research on memory reconsolidation has been booming in the last two decades, with numerous high-impact publications reporting promising amnestic interventions in rodents and humans. However, our own recently-published failed replication attempts of reactivation-dependent amnesia for fear memories in rats suggest that such amnestic effects are not always readily found and that they depend on subtle and possibly uncontrollable parameters. The discrepancy between our observations and published studies in rodents suggests that the literature in this field might be biased. The aim of the current study was to gauge the presence of publication bias in a well-delineated part of the reconsolidation literature. To this end, we performed a systematic review of the literature on reactivation-dependent amnesia for contextual fear memories in rodents, followed by a statistical assessment of publication bias in this sample. In addition, relevant researchers were contacted for unpublished results, which were included in the current analyses. The obtained results support the presence of publication bias, suggesting that the literature provides an overly optimistic overall estimate of the size and reproducibility of amnestic effects. Reactivation-dependent amnesia for contextual fear memories in rodents is thus less robust than what is projected by the literature. The moderate success of clinical studies may be in line with this conclusion, rather than reflecting translational issues. For the field to evolve, replication and non-biased publication of obtained results are essential. A set of tools that can create opportunities to increase transparency, reproducibility and credibility of research findings is provided.

Highlights

Amnesia for previously acquired memories can be obtained by applying certain treatments shortly before or after memory reactivation
Based on the inclusion criteria described in the methods section, those conditions in which amnestic effects were not hypothesized to occur, were not included in the present meta-analysis given that we aimed to study the occurrence of reactivation-dependent amnesia under optimal standard conditions
The wide range of drugs that has been used with the purpose of inducing reactivation-dependent amnesia for contextual fear memories in rodents is shown in Table 3 and Table 4

Summary

Introduction

Amnesia for previously acquired memories can be obtained by applying certain treatments shortly before or after memory reactivation. Studies revealed that memory reactivation does not occur each time a memory is retrieved but depends on the conditions under which the memory was acquired and retrieved (e.g., memory strength, age, type, or the amount of novelty introduced during the reactivation session; Tronson and Taylor, 2007). Apart from those controlled studies that examined limiting factors on memory destabilization, there have been only few papers reporting failures to obtain reactivation-dependent amnesia under standard conditions. Published failures mainly involved pharmacologically-induced amnesia in human participants (Bos et al, 2014; Thome et al, 2016; Schroyens et al, 2017) or the retrieval-extinction effect (Soeter and Kindt, 2011; Luyten and Beckers, 2017; Chalkia et al, 2020a), whereas the literature on pharmacologically-induced amnesia for fear memories in rodents shows robust and consistent amnestic effects, with hardly any failures to replicate

Objectives

Methods

Results

Conclusion