Preventing the return of fear in humans using reconsolidation update mechanisms

TLDR: The adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories is demonstrated, and a non-invasive technique that can be used safely in humans to prevent the return of fear is suggested.

Abstract: Recent research on changing fears has examined targeting reconsolidation. During reconsolidation, stored information is rendered labile after being retrieved. Pharmacological manipulations at this stage result in an inability to retrieve the memories at later times, suggesting that they are erased or persistently inhibited. Unfortunately, the use of these pharmacological manipulations in humans can be problematic. Here we introduce a non-invasive technique to target the reconsolidation of fear memories in humans. We provide evidence that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed, an effect that lasted at least a year and was selective only to reactivated memories without affecting others. These findings demonstrate the adaptive role of reconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely in humans to prevent the return of fear. Learning about potential dangers in the environment is critical for adaptive function, but at times fear learning can be maladaptive, resulting in excessive fear and anxiety. Research on changing fears has highlighted several techniques, most of which rely on the inhibition of the learned fear response. An inherent problem with these inhibition techniques is that the fear may return, for example with stress 1 . Recent research on changing fears targeting the reconsolidation process overcomes this challenge to some extent. During reconsolidation,storedinformationisrenderedlabileafterbeingretrieved, andpharmacological manipulationsatthisstageresultinaninability to retrieve the memories at later times, suggesting that they are either erased or persistently inhibited 2–6 . Although these pharmacological manipulations are potentially useful for changing learned fears, their use in humans can be problematic. Here we show that invasive techniques are not necessary to alter fear by targeting reconsolidation. This is based on the premise that reconsolidation is an adaptive update mechanism by which new information is incorporated into old memories 3,7,8 .By introducing newinformation during the reconsolidation period, it may be possible to permanently change the fear memory. In the present study, we provide evidence in humans that old fear memories can be updated with non-fearful information provided during the reconsolidation window. As a consequence, fear responses are no longer expressed. Furthermore, this effect is specific tothe targeted fear memory, and not others, and persists forat least a year.Thesefindingsdemonstratetheadaptiveroleofreconsolidation as a window of opportunity to rewrite emotional memories, and suggest a non-invasive technique that can be used safely and flexibly in humans to prevent the return of fear.