Systematically investigating the role of context on effect replicability in reinstatement of fear in humans.

Context is crucial in guiding behavior in an ever-changing world and contextual information plays a crucial role in associative learning processes. For instance, the return of fear (RoF) after successful extinction, which is used to study the mechanisms underlying relapse phenomena in fear- and stress-related disorders in an experimental model, is known to be context dependent as evident from phenomena such as renewal (contextual change) and reinstatement (re-exposure to an aversive event). Human adaptions of reinstatement paradigms have resulted in mixed findings: CS specific as well as unspecific RoF or unexpected "reinstated" conditioned responding in no reinstatement US control groups. Here, we systematically investigate the role of context (i.e., cue-context compound) on reinstatement-induced RoF in a human differential fear conditioning paradigm using subjective and psychophysiological measures in a large sample (N = 212) including reinstatement and control groups. Overall, response patterns in reinstatement-groups mirrored results from single-cue rodent work. Yet, only generalized, not differential RoF was observed. Remarkably, depending on outcome measure RoF was also observed under identical experimental context conditions without US-re-exposure, underlining effects of contextual change beyond the reinstatement-US and challenging reinstatement research in human subjects and highlight that future reinstatement work should focus on the operationalization of context.