Investigating the efficacy of the reminder-extinction procedure to disrupt contextual threat memories in humans using immersive Virtual Reality

Abstract

Upon reactivation, consolidated memories can enter a temporary labile state and require restabilisation, known as reconsolidation. Interventions during this reconsolidation period can disrupt the reactivated memory. However, it is unclear whether different kinds of memory that depend on distinct brain regions all undergo reconsolidation. Evidence for reconsolidation originates from studies assessing amygdala-dependent memories using cue-conditioning paradigms in rodents, which were subsequently replicated in humans. Whilst studies providing evidence for reconsolidation of hippocampus-dependent memories in rodents have predominantly used context conditioning paradigms, studies in humans have used completely different paradigms such as tests for wordlists or stories. Here our objective was to bridge this paradigm gap between rodent and human studies probing reconsolidation of hippocampus-dependent memories. We modified a recently developed immersive Virtual Reality paradigm to test in humans whether contextual threat-conditioned memories can be disrupted by a reminder-extinction procedure that putatively targets reconsolidation. In contrast to our hypothesis, we found comparable recovery of contextual conditioned threat responses, and comparable retention of subjective measures of threat memory, episodic memory and exploration behaviour between the reminder-extinction and standard extinction groups. Our result provide no evidence that a reminder before extinction can prevent the return of context conditioned threat memories in humans.

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

“…The conclusion drawn by Houtekamer et al [79] from this study of the retrieval-extinction protocol applied to human contextual fear memory was (p. 12), "we found no evidence that the reminder-extinction procedure is a more effective procedure to modify contextual threat conditioned memories in humans as compared to regular extinction. "…”

“…If Houtekamer et al [79] had used 100% reinforcement at acquisition, the same Day 2 procedure for the retrieval-extinction group would have created a memory mismatch and a PE experience due to the single no-shock visit to the CTX+, which would have produced destabilization and emotional memory annulment, by this analysis. Testing that prediction could provide an important confirmation of this analysis.…”

“…Therefore, each of those unexpected perceptions created a PE experience, destabilizing the target memory and allowing its unlearning and annulment, according to the framework proposed in Section 3.3.1. (In clear contrast, the post-reactivation transitions carried out by Zuccolo and Hunziker [48] and by Houtekamer et al [79], reviewed in Sections B.11 and B.13, respectively, caused subjects to view the coming video as not being part of the study, which induced a change of latent cause of the video and, therefore, neither a PE experience nor destabilization nor memory updating occurred, making these studies replication failures.) Kitamura et al [64] (p. 13) state, "Given that both low and high partial reinforcement groups did not demonstrate recovery of conditioned responses to the PRE stimulus, we conclude that a stronger memory formed as a result of a high partial reinforcement schedule does not function as a boundary condition of post-retrieval extinction."…”

“…Most authors, like Schiller et al [7], indicate only the content of the 10-min period and very little or nothing about the transition. Exceptions are the explicit transition details provided by Junjiao et al [63], Kitamura et al [64], and Chen et al [67] (in Table 1) and Houtekamer et al [79] and Zuccolo and Hunziger [77] (in Table 2). In each of those cases, the transition details can explain why the study produced a replication success or failure.…”

“…13. 2020 Houtekamer et al [79]: "Investigating the efficacy of the reminder-extinction procedure to disrupt contextual threat memories in humans using immersive Virtual Reality"…”