Destabilizing Different Strengths of Fear Memories Requires Different Degrees of Prediction Error During Retrieval

Abstract

Reactivation of consolidated memories can induce a labile period, in which these reactivated memories might be susceptible to change and need reconsolidation. Prediction error (PE) has been recognized as a necessary boundary condition for memory destabilization. Moreover, memory strength is also widely accepted as an essential boundary condition to destabilize fear memory. This study investigated whether different strengths of conditioned fear memories require different degrees of PE during memory reactivation in order for the memories to become destabilized. Here, we assessed the fear-potentiated startle and skin conductance response, using the post-retrieval extinction procedure. A violation of expectancy (PE) was induced during retrieval to reactivate enhanced (unpredictable-shock) or ordinary (predictable-shock) fear memories that were established the day before. Results showed that a PE retrieval before extinction can prevent the return of predictable-shock fear memory but cannot prevent the return of unpredictable-shock fear memory, indicating that a single PE is insufficient to destabilize enhanced fear memory. Therefore, we further investigated whether increasing the degree of PE could destabilize enhanced fear memory using different retrieval strategies (multiple PE retrieval and unreinforced CS retrieval). We found that spontaneous recovery of enhanced fear memory was prevented in both retrieval strategies, but reinstatement was only prevented in the multiple PE retrieval group, suggesting that a larger amount of PE is needed to destabilize enhanced fear memory. The findings suggest that behavioral updating during destabilization requires PE, and the degree of PE needed to induce memory destabilization during memory retrieval depends on the strength of fear memory. The study indicates that memory reconsolidation inference can be used to destabilize stronger memories, and the findings shed lights on the treatment of posttraumatic stress disorders and anxiety disorders.

Reconsolidation behavioral updating of human emotional memory: A comprehensive review and unified analysis of successes, replication failures, and clinical translation

“…Some of those studies have concluded explicitly that memory reactivation alone does not induce destabilization, e.g., [108,109]. Three of the most recent additions to that list [61,63,65] have for the first time tested the necessity of PE in the behavioral updating of human emotional memory, again confirming the PE requirement (as reviewed in Sections A. 14, A.16, and A.18).…”

“…These considerations also bear upon the findings of a sizable number of studies showing that reactivation mismatch has to be moderate, neither too mild nor too strong, in order to destabilize a memory, e.g., [22,59,65,[131][132][133][134][135][136][137]]. An inverted-U graph of destabilization probability versus degree of reactivation mismatch has been described [135].…”

“…P n/a n/a n/a n/a n/a n/a n/a n/a n/a [A.17] 2020 Kitamura [64] P Fear response is annulled at both 40% & 80% shock US pairing in replication of experiment 2 of Schiller et al (2010); CS-reactivation brings CSspecific memory annulment; SCR; US expectancy rating after reactivation P n/a n/a n/a n/a n/a n/a n/a n/a n/a [A.18] 2021 Chen [65] P 100% shock US pairing; each CS+ paired with two shocks; FPS & SCR; fear memories of different strengths were reactivated with different degrees of mismatch; stronger fear needs greater reactivation mismatch to create PE that induces destabilization.…”

“…Numerous studies of PE in relation to MR have used systematic parameter variations of the acquisition training and/or reactivation conditions and in that way have shown that the entire content of a target learning, including all details of the percepts, sequences, intensities, uncertainties, time durations, spatial positions, latent causes in the acquisition training, and environmental context, determines whether particular reactivation conditions do, or do not, create a PE experience [22,59,65,[131][132][133][134][135][136][137]. As summarized by Junjiao et al [63] (p. 294), "The prediction error is defined by the interaction between the information in the reminder session and the learning history."…”

“…Each of the indicated threshold levels of degree of mismatch, DOMPE and DOMLC, depends on and varies with many parameters, including the strength of the acquisition training, the predictive uncertainty in the acquisition training (i.e., the reinforcement schedule), the specific feature(s) of the acquisition training being mismatched, and many subject-specific variables including level of trait anxiety, tolerance for uncertainty, internal style of contextual organization of experience, and allelic differences [88,141]. In studies with 100% reinforcement during acquisition training, reactivation by a single unreinforced conditioned stimulus is a very strong mismatch because it is an absolute and total contradiction of the expected CS-US pairing, yet destabilization and memory annulment are observed to result [58,65,88,109,142], indicating that though the mismatch was strong, it also had strong, clear relevance to the target memory, therefore it created a PE experience rather than a change of latent cause. New latent causes are induced by mismatches that the subject discerns as evidence of a different type of experience or phenomenon, and apparently that qualitative discernment is not simply a matter of strength of mismatch.…”