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The ability to perceive and feel another person' pain as if it were one's own pain, e.g., pain empathy, is related to brain activity in the “pain-matrix” network. A non-core region of this network in Dorsolateral Prefrontal Cortex (DLPFC) has been suggested as a modulator of the attentional-cognitive dimensions of pain processing in the context of pain empathy. We conducted a neurofeedback experiment using real-time functional magnetic resonance imaging (rt-fMRI-NF) to investigate the association between activity in the left DLPFC (our neurofeedback target area) and the perspective assumed by the participant (“first-person”/“Self” or “third-person”/“Other” perspective of a pain-inducing stimulus), based on a customized pain empathy task. Our main goals were to assess the participants' ability to volitionally modulate activity in their own DLPFC through an imagery task of pain empathy and to investigate into which extent this ability depends on feedback. Our results demonstrate participants' ability to significantly modulate brain activity of the neurofeedback target area for the “first-person”/”Self” and “third-person”/”Other” perspectives. Results of both perspectives show that the participants were able to modulate (with statistical significance) the activity already in the first run of the session, in spite of being naïve to the task and even in the absence of feedback information. Moreover, they improved modulation throughout the session, particularly in the “Self” perspective. These results provide new insights on the role of DLPFC in pain and pain empathy mechanisms and validate the proposed protocol, paving the way for future interventional studies in clinical populations with empathic deficits.

Volitional Modulation of the Left DLPFC Neural Activity Based on a Pain Empathy Paradigm—A Potential Novel Therapeutic Target for Pain