Perturbing and measuring neural activity in the pain resonance network: TMS studies

Transcranial magnetic stimulation (TMS) studies show that watching painful stimuli delivered to the hand of a human model induces a decrease of corticospinal excitability in the onlooker’s muscle correspondent to the one punctured in the model. This muscle-specific, pain observation-related inhibition (PORI) is similar to that found during actual pain perception, suggesting that seeing pain in others triggers pain embodied resonance in the onlooker’s corticospinal system. However, information on the relation between PORI and the activity of sensorimotor cortical regions recruited during pain perception is meager. Using TMS, in two experiments, we provide causal evidence that the primary somatosensory (S1), motor (M1) and premotor (PMc) cortices play distinct and critical roles in PORI. We used a perturb-and-measure TMS paradigm, combining repetitive TMS (1Hz-rTMS, to suppress neural activity in selected cortical regions) and single-pulse TMS (spTMS) during pain observation (to assess PORI). We applied MRI-guided rTMS over the hand representation in PMc, M1, S1 and visual cortex (V1, control area) and tested their role in modulating PORI. In keeping with previous studies, a standard PORI effect was found in a no rTMS condition. The effect was stronger in the subjects who showed greater dispositional empathy (assessed by the Interpersonal Reactivity Index) and provided higher observed-pain scores. PORI was suppressed and increased by M1 and S1 disruption, respectively and left unaffected by V1 disruption. Importantly, disruption of PMc changed the PORI into a muscle-specific facilitatory response. Thus, while S1 normal functioning seems to keep under control a potentially excessive embodiment of others’ pain, normal functioning of PMc and M1 exert a same-direction, different-strength modulatory effect that allow an optimal tuning of resonant corticospinal mapping of observed pain. Our findings highlight the causal connectivity between PMc-M1-S1 regions and the corticospinal system during embodied empathy for pain