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Preventing the return of fear in humans using reconsolidation update mechanisms

An Addendum to this article was published on 26 July 2018


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.

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Figure 1: Extinction during reconsolidation prevents spontaneous recovery of extinguished fear.
Figure 2: Blockade of the return of fear persists one year later.
Figure 3: Blockade of the return of fear is specific to reactivated memories.


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Acknowledgement We thank K. Doelling for assistance with data collection and discussions on the revised version of the manuscript. We also thank Y. Niv and M. Milad for advice on the experimental protocols. This study was funded by the James S. McDonnell Foundation and National Institutes of Health (NIH) grant R21 MH072279 (E.A.P.), NIH grants R37 MH038774, P50 MH058911, RO1 MH046516 and K05 MH067048 (J.E.L.), Postdoctoral fellowships NSERC, CIHR and AHFMR (M.-H.M.), and a Fulbright award (D.S.).

Author Contributions D.S. designed the experiments, collected and analysed data, interpreted the data and wrote the first draft of the manuscript; C.M.R. and D.C.J. collected the data and contributed to experimental design, analysis, interpretation and the final version of the manuscript; M.-H.M., J.E.L. and E.A.P. contributed to experimental design, data interpretation, and the final version of the manuscript.

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Correspondence to Elizabeth A. Phelps.

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Schiller, D., Monfils, MH., Raio, C. et al. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463, 49–53 (2010).

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