Attentional set to safety recruits the medial prefrontal cortex

During threat assessment, the early detection of danger is highly adaptive, yet the fast orientation towards safety is also key to survival. The present study aimed to explore how the human brain searches for safety by manipulating subjects’ attentional set to cues associated with shock probability. Subjects were asked to judge random dots motion (RDM) direction and could be shocked for incorrect responses (RDM task) while keeping alert in detecting the shock probability cues (cue detection task). In contrast to the safe condition, where subjects searched for cues associated with no shock probability, incorrect responses to ‘dangerous+’ (D+) cues would increase the shock probability and correct responses to ‘dangerous-’ (D-) cues would decrease shock probability. In the RDM task, results showed that relative to the D+, the safe attentional set resulted in stronger activation in the ventral medial prefrontal cortex (vmPFC), a core region involved in flexible threat assessment and safety signalling. The vmPFC was also recruited by the D-compared to the D + attentional set. In the cue detection task, shorter response times and greater accuracy were observed for D+ compared to D‐ and safe cues. Correspondingly, at the neural level D+ cues induced increased activity in the frontoparietal attention network including the inferior parietal lobule and intraparietal sulcus. Overall, our findings demonstrate that attentional set for searching safety recruits the vmPFC, while detection of threat elicits activity in the frontoparietal attention network, suggesting a new role for these regions in human defensive survival circuitry. Significance Statement While early detection of threat is highly adaptive, the fast orientation towards safety is also key to survival. However, little is known about neural mechanisms underlying attentional set to safety. Using a novel dots motion paradigm combined with fMRI, we explored how human brain prepares for safety searching by manipulating subjects’ attentional set to cues associated with shock probability. Relative to the dangerous attentional set associated with increasing shock probability, the safe attentional set resulted in stronger activity in the ventral medial prefrontal cortex, a core region involved in flexible threat assessment and safety signalling, suggesting a new role for this region in human defensive survival system in encoding stimuli with survival significance.