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Empathy for the social suffering of friends and strangers recruits distinct patterns of brain activation.

Humans observe various peoples' social suffering throughout their lives, but it is unknown whether the same brain mechanisms respond to people we are close to and strangers' social suffering. To address this question, we had participant's complete functional magnetic resonance imaging (fMRI) while observing a friend and stranger experience social exclusion. Observing a friend's exclusion activated affective pain regions associated with the direct (i.e. firsthand) experience of exclusion [dorsal anterior cingulate cortex (dACC) and insula], and this activation correlated with self-reported self-other overlap with the friend. Alternatively, observing a stranger's exclusion activated regions associated with thinking about the traits, mental states and intentions of others ['mentalizing'; dorsal medial prefrontal cortex (DMPFC), precuneus, and temporal pole]. Comparing activation from observing friend's vs stranger's exclusion showed increased activation in brain regions associated with the firsthand experience of exclusion (dACC and anterior insula) and with thinking about the self [medial prefrontal cortex (MPFC)]. Finally, functional connectivity analyses demonstrated that MPFC and affective pain regions activated in concert during empathy for friends, but not strangers. These results suggest empathy for friends' social suffering relies on emotion sharing and self-processing mechanisms, whereas empathy for strangers' social suffering may rely more heavily on mentalizing systems.