Effects of Experiencing CS-US Pairings on Instructed Fear Reversal

Fear learning allows us to identify and anticipate aversive events and adapt our behavior accordingly. This is often thought to rely on associative learning mechanisms where an initially neutral conditioned stimulus (CS) is repeatedly paired with an aversive uncondi-tioned stimulus (US), eventually leading to the CS also being perceived as aversive and threatening. Importantly, however, humans also show verbal fear learning. Namely, they have the ability to change their responses to stimuli rapidly through verbal instructions about CS-US pairings. Past research on the link between experience-based and verbal fear learning indicated that verbal instructions about a reversal of CS-US pairings can fully override the effects of previously experienced CS-US pairings, as measured through fear ratings, skin conductance, and fear-potentiated startle. However, it remains an open question whether such instructions can also annul learned CS representations in the brain. Here, we used a fear reversal paradigm (female and male participants) in conjunction with representational similarity analysis of fMRI data to test whether verbal instructions fully override the effects of experienced CS-US pairings in fear-related brain regions or not. Previous research suggests that only the right amygdala should show lingering represen-tations of previously experienced threat ("pavlovian trace"). Unexpectedly, we found evidence for the residual effect of prior CS-US experience to be much more widespread than anticipated, in the amygdala but also cortical regions like the dorsal anterior cingulate or dorsolateral prefrontal cortex. This finding shines a new light on the interaction of different fear learning mechanisms, at times with unexpected consequences.