Neurophysiological encoding of aversive prediction errors.

Aversive prediction error (PE) brain signals generated by unexpected pain or pain absence are crucial for learning to avoid future pain. Yet, the detailed neurophysiological origins of PE signaling remain unclear. In this study, we combined an instrumental pain avoidance task with computational modeling and magnetoencephalography to detect time-resolved activations underlying pain expectations and aversive PE signals in the human brain. The task entailed learning probabilistically changing cue-pain associations to avoid receiving a pain stimulus. We used an axiomatic approach to identify general aversive PE signals that encode the degree to which the outcome deviated from expectations. Our findings indicate that aversive PE signals are generated in the alpha band (8-12 Hz) by the midbrain/diencephalon, lateral orbitofrontal cortex, and ventrolateral prefrontal cortex approximately 150 milliseconds after outcome delivery. Moreover, alpha oscillations in these regions also encoded pain expectations before the outcome. We speculate that this may facilitate the rapid generation of PEs by allowing outcome-related nociceptive activity to be integrated with ongoing predictive signals. Finally, decisions to avoid pain recruited alpha oscillations in the anterior cingulate and dorsomedial prefrontal cortices, suggesting their active engagement in comparing predicted action values. Overall, our data reveal the rapid neurophysiological mechanisms underlying the generation of aversive PEs and subsequent decision-making.