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.
Highlights
A brief reminder can return consolidated memories to a labile state, requiring re-stabilization processes to maintain the memory, a process referred to as reconsolidation[1,2], but s ee[3,4,5] for alternative accounts
An immersive Virtual Reality contextual threat conditioning paradigm for humans was developed, which provides people with a sense of immersion in a virtual environment and allows people to learn an association between a particular contextual environment and an aversive outcome in the absence of a discrete cue signalling the outcome
Following the acquisition of contextual threat conditioning, fifty-seven out of sixty participants could explicitly state the relationship between the conditioned contexts and shocks, indicating that they learned the conditioned association
Summary
A brief reminder can return consolidated memories to a labile state, requiring re-stabilization processes to maintain the memory, a process referred to as reconsolidation[1,2], but s ee[3,4,5] for alternative accounts. People with stress- and anxiety-disorders generally experience several different forms of maladaptive memory expression, such as excessive threat responses, subjective negative feelings, emotional episodic memories, and avoidance behaviours[14,15,16,17] To date it is still unclear whether all kinds of memory undergo reconsolidation and whether these are sensitive to reconsolidation-targeting interventions. An immersive Virtual Reality (iVR) contextual threat conditioning paradigm for humans was developed, which provides people with a sense of immersion in a virtual environment and allows people to learn an association between a particular contextual environment and an aversive outcome in the absence of a discrete cue signalling the outcome This iVR context conditioning paradigm was shown to result in the acquisition of contextual threat-conditioned defensive responses, subjective feelings of threat, and episodic memory for details of the threatening spatiotemporal c ontext[40]. As similar VR contextual threat conditioning paradigms have been shown to involve hippocampal processing in humans (Ref.[41] and see Ref.[40] for a review), this iVR contextual threat conditioning paradigm provides an opportunity to investigate reconsolidation of contextual threat conditioned memories that are likely hippocampus-dependent and comparable to memories in studies using contextual threat conditioning procedures in rodents
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