Model-based aversive learning in humans is supported by preferential task state reactivation.

Harm avoidance is critical for survival, yet little is known regarding the neural mechanisms supporting avoidance in the absence of trial-and-error experience. Flexible avoidance may be supported by a mental model (i.e., model-based), a process for which neural reactivation and sequential replay have emerged as candidate mechanisms. During an aversive learning task, combined with magnetoencephalography, we show prospective and retrospective reactivation during planning and learning, respectively, coupled to evidence for sequential replay. Specifically, when individuals plan in an aversive context, we find preferential reactivation of subsequently chosen goal states. Stronger reactivation is associated with greater hippocampal theta power. At outcome receipt, unchosen goal states are reactivated regardless of outcome valence. Replay of paths leading to goal states was modulated by outcome valence, with aversive outcomes associated with stronger reverse replay than safe outcomes. Our findings are suggestive of avoidance involving simulation of unexperienced states through hippocampally mediated reactivation and replay.