Young and old Pavlovian fear memories can be modified with extinction training during reconsolidation in humans

Abstract

Extinction training during reconsolidation has been shown to persistently diminish conditioned fear responses across species. We investigated in humans if older fear memories can benefit similarly. Using a Pavlovian fear conditioning paradigm we compared standard extinction and extinction after memory reactivation 1 d or 7 d following acquisition. Participants who underwent extinction during reconsolidation showed no evidence of fear recovery, whereas fear responses returned in participants who underwent standard extinction. We observed this effect in young and old fear memories. Extending the beneficial use of reconsolidation to older fear memories in humans is promising for therapeutic applications.[Supplemental material is available for this article.]Learning to predict threat from cues in the environment is adaptive. In order to remain adaptive, however, the memory of the association between a neutral cue and a threat cue, as well as the elicited fear response or defensive behavior, needs to be flexibly modified as situations change. The standard approach to modify fear is extinction or exposure training in which a new, safe association is learned, leading to a gradually diminished fear expression. With extinction, however, fear might return because the original fear memory is not significantly altered and must be inhibited to express the new extinction memory (Bouton 2004). It has been suggested that the inability to consistently inhibit fear memories following extinction or exposure may be a factor in the maladaptive expression of fear in anxiety, trauma, or stress-related disorders, such as post-traumatic stress disorder (PTSD) (Rauch et al. 2006). The potentially temporary nature of extinction or exposure training led to the search for strategies to more persistently alter fear memories, which renewed interest in the post-retrieval memory process of reconsolidation. Reconsolidation is a restabilization process triggered by the retrieval of the original memory (Duvarci and Nader 2004). Interventions that interfere with reconsolidation can persistently alter the expression of fear memories (Nader et al. 2000;Schiller et al. 2010). However, to derive a viable therapeutic technique based on disrupting reconsolidation, it is critical that both recently formed and older fear memories can be altered. Since memories of trauma are often formed long before treatment opportunities are available, it is important to characterize the effectiveness of reconsolidation for older memories. To date, there is little evidence in humans demonstrating the efficacy of targeting reconsolidation to diminish the expression of fear memories .1 d old. The goal of the present study was to start to bridge this gap by targeting reconsolidation in 7-d-old fear memories.Two primary techniques have been used to target the reconsolidation of fear memories: pharmacological and behavioral. These studies have examined fear memories using Pavlovian fear conditioning, in which an aversive unconditioned stimulus (UCS) is paired with a neutral co...

Delayed extinction fails to reduce skin conductance reactivity to fear‐conditioned stimuli

“…The failure to “update” and interfere with the reconsolidation process using a nonpharmacological intervention observed in the present study is at odds with the findings of Agren, Engman et al (), Agren, Furmark, Eriksson, & Fredrikson (), Oyarzun et al (), Schiller et al (), and Steinfurth et al (), but consistent with prior negative results reported by Golkar et al (), Kindt and Soeter (), and Soeter and Kindt (). The explanation for the inconsistent findings across studies is not readily apparent, but seems unlikely to be due to procedural differences (see Golkar et al, ).…”

Modulating reconsolidation: a link to causal systems-level dynamics of human memories

“…These results are consistent with animal work using a similar protocol [34] and were replicated in later studies [60,61]. Recent findings suggest that, similar to young memories [59], older fear memories can also be updated and attenuated using extinction training after memory reactivation [62]. In addition, it has been shown that for labilization of fear memory to occur, new information has to be presented during reactivation (prediction error) [19] as demonstrated in animal work [16-18], supporting the notion that a function of reconsolidation is memory updating.…”

Persistence and plasticity in the human memory system: An empirical investigation of the overwriting hypothesis

“…For instance, reconsolidation e ects have been observed with training-reminder intervals at 1d but not 8d (Forcato et al, 2013), 6d but not 20d (Coccoz et al, 2013), 2d and 7d, but not 14d or 28d (Milekic & Alberini, 2002), and 1d and 28d, but not 7d (Wichert et al, 2011). However, other studies have observed reconsolidation e ects for 'older' memory traces, with training-reminder intervals of 7d (Steinfurth et al, 2014), 14d (Nader et al, 2000a), 30d (Einarsson & Nader, 2012), and 60d (DÍbiec & LeDoux, 2004). A boundary condition of memory age also seems incompatible with the notion that expect, and what actually happens (Forcato et al, 2009;Pedreira et al, 2004;Morris et al, 2006;Rodriguez-Ortiz, 2005;Sevenster, Beckers, & Kindt, 2014).…”