Top-down influence of the inferior frontal gyrus on motor cortex excitability during pain empathy.

Empathy for pain can reduce activity in the observer's motor system, but the neural processes that shape this response remain unclear. Here we show that observing another person in pain reduces corticospinal excitability and increases perceived pain intensity when viewed from a first-person perspective, but not from a third-person perspective. This motor suppression is absent when noxious events are applied to a non-biological object. Using single-pulse, paired-pulse, and dual-site transcranial magnetic stimulation, we find no detectable change in local motor cortical inhibitory or facilitatory circuits, but observe a pain-specific reduction in the connectivity index between the inferior frontal gyrus and primary motor cortex. This effect covaries with perceived pain intensity and motor suppression and is site-specific relative to a Vertex control condition. Bayesian network modeling further suggests that perceived pain intensity predicts both unpleasantness and motor excitability. Together, these findings suggest that pain appraisal may be associated with frontal-motor interactions during pain empathy.