Preventing the return of fear in humans using reconsolidation update mechanisms

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.

Figure 1. Extinction during reconsolidation prevents spontaneous recovery of extinguished fear

(a) Experimental design and timeline. (b) Mean differential SCRs (CS+ minus CS−) during acquisition (late phase), extinction (last trial) and re-extinction (first trial) for each experimental group (10 min reminder, 6 hr reminder, and no-reminder). The three groups showed equivalent fear acquisition and extinction. Spontaneous recovery (first trial of re-extinction versus the last trial of extinction) was found in the group that had not been reminded or that was reminded 6 hours prior to extinction. In contrast, there was no spontaneous recovery in the group reminded 10 min before extinction. *Significant difference between acquisition and extinction, or extinction and re-extinction within group at p < 0.05; Error bars represent standard errors

Figure 2. Blockade of the return of fear persists one year later

The reinstatement index is the difference in the conditioned fear response (CS+ minus CS−) at the end of re-extinction following the initial spontaneous recovery test and the conditioned fear response immediately after reinstatement a year later. The magnitude of the reinstatement was significantly higher in the 6 hr / no-reminder group compared to the 10 min group, which showed no reinstatement. *Significant difference at p < 0.05; Error bars represent standard errors

Figure 3. Extinction during reconsolidation prevents reinstatement of extinguished fear

(a) Experimental design and timeline. (b) Mean SCRs (CSa+, CSb+, CS−) during acquisition (late phase), extinction (last trial) and re-extinction (first trial). Subjects had equivalent levels of acquisition and extinction of conditioned fear to the two conditioned stimuli. The index of fear recovery was the first trial of re-extinction (following reinstatement) minus the last trial of extinction (before reinstatement). Fear reinstatement was found only to CSb+, (not reminded before extinction training) but not CSa+ (reminded 10 min before extinction training). *Significant difference between acquisition and extinction, or extinction and re-extinction for each stimulus at p < 0.05; Error bars represent standard errors