Harm avoidance is critical for survival, yet little is known regarding the underlying neural mechanisms supporting avoidance when we cannot rely on direct trial and error experience. Neural reactivation, and sequential replay, have emerged as potential candidate mechanisms. Here, during an aversive learning task, in conjunction with magnetoencephalography, we show prospective and retrospective reactivation for planning and learning respectively, coupled to evidence for sequential replay. Specifically, when subjects plan in an aversive context, we find preferential reactivation of subsequently chosen goal states and sequential replay of the preceding path. This reactivation was associated with greater hippocampal theta power. At outcome receipt, unchosen goal states are reactivated regardless of outcome valence. However, replay of paths leading to goal states was directionally modulated by outcome valence, with aversive outcomes leading to stronger reverse replay compared to safe outcomes. Our findings suggest that avoidance behaviour involves simulation of alternative future and past outcome states through hippocampally-mediated reactivation and replay.

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.