Neural interactions in the human frontal cortex dissociate reward and punishment learning.

How human prefrontal and insular regions interact while maximizing rewards and minimizing punishments is unknown. Capitalizing on human intracranial recordings, we demonstrate that the functional specificity toward reward or punishment learning is better disentangled by interactions compared to local representations. Prefrontal and insular cortices display non-selective neural populations to rewards and punishments. Non-selective responses, however, give rise to context-specific interareal interactions. We identify a reward subsystem with redundant interactions between the orbitofrontal and ventromedial prefrontal cortices, with a driving role of the latter. In addition, we find a punishment subsystem with redundant interactions between the insular and dorsolateral cortices, with a driving role of the insula. Finally, switching between reward and punishment learning is mediated by synergistic interactions between the two subsystems. These results provide a unifying explanation of distributed cortical representations and interactions supporting reward and punishment learning.