Modulation of naturalistic maladaptive memories using behavioural and pharmacological reconsolidation-interfering strategies: A systematic review and meta-analysis of clinical and 'sub-clinical' studies

Abstract

Consolidated memories can undergo enduring modification through retrieval-dependent treatments that modulate reconsolidation. This has been suggested to represent a potentially transformative clinical strategy for weakening or overwriting the maladaptive memories that underlie substance use and anxiety/trauma-related disorders. However, the ability to modulate naturalistic maladaptive memories may be limited by 'boundary conditions' imposed on reconsolidation by the nature of these memories. As such, the true potential of 'reconsolidation therapy' is currently unknown. Here, we report a meta-analyses of behavioural and pharmacological studies examining retrieval-dependent modulation of reward and threat memories in (sub)clinical substance use and anxiety/trauma respectively.Of 4936 publications assessed for eligibility, 7 studies of substance use, and 9 of anxiety (phobia) and trauma-related symptoms were included in the meta-analyses. Overall, the findings were in the predicted direction, with the majority of effect sizes favouring the 'Retrieval + Treatment' condition. However, the magnitude of effects depended upon the nature of the treatment type, with pharmacological interventions (relative to behavioural strategies) showing a clearer beneficial effect in studies of phobia/trauma and post-retrieval behavioural strategies, a (significantly) larger effect in substance use studies. However, high levels of heterogeneity and small sample sizes limit the strength of conclusions that can be drawn at this stage of inquiry. We hope this review will provide an impetus to address these issues in future research.

Memory editing from science fiction to clinical practice

“…Because of the overlap between laboratory extinction paradigms and exposure therapies, integrating editing techniques into this type of clinical therapy is relatively straightforward. So far, this approach has shown little to modest success in preclinical studies 82 . Optimizing the integration of memory editing into exposure therapy will require the identification of methods to overcome the boundaries of reconsolidation 8 , as well as an understanding of how targeting reconsolidation of one memory type (such as defensive responses) alters other means of memory expression (such as negative subjective feelings and episodic memory).…”

Ketamine Can Reduce Harmful Drinking by Pharmacologically Rewriting Drinking Memories

“…Reliable pharmacological MRM rewriting remains elusive, however, due to the relative difficulty in reactivating/destabilizing inherently robust MRMs in human drug users and the severely limited menu of well-tolerated reconsolidation blockers 15 . Indeed, most preclinical studies of reconsolidation involve experimentally generated "models" of MRMs that are orders of magnitude weaker than true human MRMs, and also employ highly toxic compounds (with highly limited human translatability) to block reconsolidation 16 .…”

Long-term Behavioural Rewriting of Maladaptive Drinking Memories via Reconsolidation-Update Mechanisms

“…By directly re-formatting MRMs such that trigger cues do not provoke alcohol seeking, it may be possible to reduce alcohol consumption and prophylactically guard against relapse over the long-term. Although a nascent field, there have been highly promising early demonstrations of the potential of this approach (Walsh et al 2018). Extinction (i.e.…”

“…These key parameters have not been systematically manipulated in clinically-focussed reconsolidation interference studies. Most studies do not explicitly induce or test the occurrence of PE, with variable and largely heuristic retrieval lengths being employed across studies (Walsh et al 2018). It is unsurprising, then, that findings are correspondingly inconsistent.…”