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lations. Furthermore, the observed behavioral and neurophysiological effects persisted beyond the stimulations. Subjects were not aware of the stimulations, and there were no cardiovascular or untoward effects. Additional, nonpharmacological therapies are imperative for the future management of chronic pain conditions and to mitigate the ongoing opioid crisis. This study suggests that direct stimulation of the anterior insula can safely alter cerebral pain processing in humans. Further investigation of the anterior insula as a potential target for t