Empathy allows emotional psychological inference about other person's mental states and feelings in social contexts. We aimed at specifying the common and differential neural mechanisms of “self”- and “other”-related attribution of emotional states using event-related functional magnetic resonance imaging. Subjects viewed faces expressing emotions with direct or averted gaze and either focused on their own emotional response to each face (self-task) or evaluated the emotional state expressed by the face (other-task). The common network activated by both tasks included the left lateral orbito-frontal and medial prefrontal cortices (MPFC), bilateral inferior frontal cortices, superior temporal sulci and temporal poles, as well as the right cerebellum. In a subset of these regions, neural activity was significantly correlated with empathic abilities. The self- (relative to the other-) task differentially activated the MPFC, the posterior cingulate cortex (PCC)/precuneus, and the temporo-parietal junction bilaterally. Empathy-related processing of emotional facial expressions recruited brain areas involved in mirror neuron and theory-of-mind (ToM) mechanisms. The differential engagement of the MPFC, the PCC/precuneus, and temporo-parietal regions in the self-task indicates that these structures act as key players in the evaluation of one's own emotional state during empathic face-to-face interaction. Activation of mirror neurons in a task relying on empathic abilities without explicit task-related motor components supports the view that mirror neurons are not only involved in motor cognition but also in emotional interpersonal cognition. An interplay between ToM and mirror neuron mechanisms may hold for the maintenance of a self-other distinction during empathic interpersonal face-to-face interactions.

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