Reversal of fear in the human brain

Schiller et al. do work on learned fear responses and their reversal:

Fear learning is a rapid and persistent process that promotes defense against threats and reduces the need to relearn about danger. However, it is also important to flexibly readjust fear behavior when circumstances change. Indeed, a failure to adjust to changing conditions may contribute to anxiety disorders. A central, yet neglected aspect of fear modulation is the ability to flexibly shift fear responses from one stimulus to another if a once-threatening stimulus becomes safe or a once-safe stimulus becomes threatening. In these situations, the inhibition of fear and the development of fear reactions co-occur but are directed at different targets, requiring accurate responding under continuous stress. To date, research on fear modulation has focused mainly on the shift from fear to safety by using paradigms such as extinction, resulting in a reduction of fear. The aim of the present study was to track the dynamic shifts from fear to safety and from safety to fear when these transitions occur simultaneously. We used functional neuroimaging in conjunction with a fear-conditioning reversal paradigm. Our results reveal a unique dissociation within the ventromedial prefrontal cortex between a safe stimulus that previously predicted danger and a "naive" safe stimulus. We show that amygdala and striatal responses tracked the fear-predictive stimuli, flexibly flipping their responses from one predictive stimulus to another. Moreover, prediction errors associated with reversal learning correlated with striatal activation. These results elucidate how fear is readjusted to appropriately track environmental changes, and the brain mechanisms underlying the flexible control of fear.


Figure: Striatum and amygdala BOLD responses throughout the discrimination and reversal task. A, Mean differential striatal (left and right caudate) and amygdala percent BOLD signal change in the different phases of the task. The differential responding is calculated as [face A – face B]. Positive scores correspond to stronger responses to face A, which was paired with the shock during acquisition (CS+). Negative scores correspond to stronger responses to face B, which was paired with the shock during reversal (new CS+). These BOLD responses were extracted from the CS+ greater than CS– in early acquisition contrast. B, Striatal activation is denoted by yellow circle. C, Left amygdala activation is denoted by yellow circle.