Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats

Shumake, Jason; Jones, Carolyn E.; Auchter, Allison; Monfils, Marie‐H.

doi:10.1098/rstb.2017.0035

Cited by 27 publications

(23 citation statements)

References 33 publications

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“…It may be the case that unknown individual differences moderate reactivation-extinction effects. In an intriguing report, Shumake and colleagues re-analyzed older rodent datasets with the aim of detecting different phenotype subgroups based on their responding during acquisition, extinction, and reinstatement (Shumake, Jones, Auchter, & Monfils, 2018). Only two subgroups (33% of their total sample of N = 215) showed a long-term fear reduction, while the other five subgroups showed a return or persistence of fear.…”

Section: Discussionmentioning

confidence: 99%

No persistent attenuation of fear memories in humans: A registered replication of the reactivation-extinction effect

Chalkia

Schroyens

Leng

et al. 2020

Cortex

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It has been proposed that memory retrieval can destabilize consolidated memories, after which they need to be reconsolidated in order to be retained. The presentation of relevant information during memory reconsolidation could then result in the modification of a destabilized memory trace, by allowing the memory trace to be updated before being reconsolidated. In line with this idea, Schiller et al. (2010) have demonstrated that memory retrieval shortly before extinction training can prevent the later recovery of conditioned fear responding that is observed after regular extinction training. Those findings have been the subject of considerable controversy, due in part to theoretical reasons but also due to a number of failures to obtain similar results in conceptual replication attempts. Here, we report the results of a highly powered, direct, independent replication of the critical conditions of Schiller et al. (2010, Experiment 1). Due to misrepresentation of the exclusion criteria in the original Schiller et al. (2010) report, data collection was considerably delayed. When we eventually managed to attain our pre-registered sample size, we found that we could not observe any benefit of reactivation-extinction over regular extinction training in preventing recovery of conditioned fear. The results of the present study, along with the mixed findings in the literature and the misreporting in Schiller et al. (2010), give cause to question whether there is robust evidence that reactivation-extinction prevents the return of fear in humans.

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Section: Discussionmentioning

confidence: 99%

No persistent attenuation of fear memories in humans: A registered replication of the reactivation-extinction effect

Chalkia

Schroyens

Leng

et al. 2020

Cortex

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“…The subsequent repeated presenta- tion of the conditioned stimulus in the absence of a reinforcer leads to a progressive decrease in fear responding—a phe- nomenon and paradigm known as extinction. Exposure ther- apy, a therapeutic approach employed in clinical settings, shares characteristics and mechanisms with extinction, and mounting evidence suggests that there are considerable differ- ences in individual responding to both exposure therapy and extinction (Shumake et al 2014, 2018; Bush et al 2007; Galatzer-Levy et al 2013; Schwartze et al 2017). From a translational perspective, identifying whether an individual might respond well to extinction prior to intervention could prove important to treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

Predicting extinction phenotype to optimize fear reduction

Monfils

Lee

Keller³

et al. 2018

Psychopharmacology

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Fear conditioning is widely employed to study dysregulations of the fear system. The repeated presentation of a conditioned stimulus in the absence of a reinforcer leads to a decrease in fear responding-a phenomenon known as extinction. From a translational perspective, identifying whether an individual might respond well to extinction prior to intervention could prove important to treatment outcomes. Here, we test the hypothesis that CO reactivity predicts extinction phenotype in rats, and that variability in CO reactivity as well as extinction long-term memory (LTM) significantly predicts orexin activity in the lateral hypothalamus (LH). Our results validate a rat model of CO reactivity and show that subcomponents of behavioral reactivity following acute CO exposure explain a significant portion of the variance in extinction LTM. Furthermore, we show evidence that variability in CO reactivity is also significantly predictive of orexin activity in the LH, and that orexin activity, in turn, significantly accounts for LTM variance. Our findings open the possibility that we may be able to use CO reactivity as a screening tool to determine if individuals are good candidates for an extinction/exposure-based approach.

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“…One could reasonably anticipate equal (or greater) response variability when using retrievalextinction (Shumake et al 2018); a paradigm that has dominated behavioural memory rewriting research. This may partially explain the inconsistencies and difficulties replicating findings with retrieval-extinction interventions (Soeter & Kindt 2011;Baker et al 2013;Chen et al 2014;Luyten & Beckers 2017), since a failure to extinguish would preclude any potentiating effect of prior memory retrieval.…”

Section: Limitationsmentioning

confidence: 99%

“…Firstly, extinction itself may represent a sub-optimal 'corrective' learning modality, since it is a largely passive procedure, involving no response from participants, unobserved interindividual variability in engagement and responsiveness to extinction (Shumake et al 2018) may mask effects. A promising alternative -counterconditioning-re-pairs cues reward cues (e.g.…”

Section: Introductionmentioning

confidence: 99%

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

Gale

Hennessy

Walsh

et al. 2020

Preprint

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Background: Alcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are a key therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. Methods:Hazardous/harmful beer-drinking volunteers (N=120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgustbased counterconditioning of drinking cues. Acute responses to alcohol were assessed preand post-manipulation and drinking levels assessed up to 9 months.Results: Greater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning were noted. 'Responsiveness' to counterconditioning predicted subsequent responses to acute alcohol in RET+PE only, consistent with reconsolidation-update mechanisms. Conclusions: The longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.

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Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats

Cited by 27 publications

References 33 publications

No persistent attenuation of fear memories in humans: A registered replication of the reactivation-extinction effect

No persistent attenuation of fear memories in humans: A registered replication of the reactivation-extinction effect

Predicting extinction phenotype to optimize fear reduction

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

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