How cognitive and reactive fear circuits optimize escape decisions in humans

Significance Humans, like other animals, have evolved a set of neural circuits whose primary function is survival. In the case of predation, these circuits include “reactive fear” circuits involved in fast escape decisions and “cognitive fear” circuits that are involved in more complex processing associated with slow strategic escape. Using neuroimaging combined with computational modeling, we support this differentiation of fear circuits by showing that fast escape decisions are elicited by the periaqueductal gray and midcingulate cortex, regions involved in reactive flight. Conversely, slower escape decisions rely on the hippocampus, posterior cingulate cortex, and prefrontal cortex, a circuit implicated in behavioral flexibility. These results support a separation of fear into reactive and cognitive circuits. Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost–benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking “virtual predators” constrain escape decisions. We show that rapid escape decisions rely on “reactive fear” circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with “cognitive fear” circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.