Causal connectivity in the cortical network underlying embodied empathy for pain: a perturb-and-measure TMS study

Similarly to first-hand pain experience, watching painful stimuli on another person’s body decreases the excitability of the correspondent corticospinal body part representation in the observers. However, information on the relation between this pain observation-related inhibition (PORI) and the activity of sensorimotor regions recruited during pain perception is meager. Using TMS, we provide causal evidence that 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 disrupt neural activity in selected cortical regions) and single-pulse TMS (spTMS, to assess consequent changes in PORI during pain observation). We applied rTMS over PMc, M1, S1 and visual cortex (V1, control area) and tested their involvement in modulating PORI. A standard PORI effect was found in a no-rTMS condition and after V1- disruption; the effect was stronger in the subjects who showed greater dispositional empathy and provided higher ratings of the observed pain. The PORI effect was increased by S1-disruption and suppressed by M1- disruption. Importantly, PMc-disruption changed PORI into a muscle-specific facilitatory response. Thus, while normal functioning of S1 seems to keep under control a potentially excessive embodiment of others’ pain, in physiological conditions PMc and M1 may exert a same-direction, different-strength modulation that allows an optimal tuning of the tendency to embody the observed pain. Our findings highlight the causal connectivity between PMc-M1-S1 regions and the corticospinal system during vicarious experience of others’ pain and suggest that TMS can disclose specific inter-regional neural interactions during social perception.