Autonomic arousal elicited by subcallosal cingulate stimulation is explained by white matter connectivity

Abstract

BACKGROUND\nSubcallosal cingulate deep brain stimulation (SCC DBS) is an experimental treatment for severe depression. Surgery is performed with awake patients and intraoperative stimulation produces acute behavioral responses in select contacts. While there have been reports on the relationship between acute intraoperative behaviors and their relation to the location of the contacts, there are no descriptions of the physiological changes that accompany them.\n\n\nOBJECTIVE\nThe present study sought to examine these physiological readouts, and their association with the anatomical substrates that generated them.\n\n\nMETHODS\nNine patients with severe, treatment-resistant depression were tested intraoperatively. The stimulation protocol consisted of 12 three-minute, sham-controlled, double-blind trials. Changes in heart rate and skin conductance were recorded during each stimulation cycle. Probabilistic tractography between the stimulated contacts and predefined regions of the mood regulation network was performed.\n\n\nRESULTS\nAcute intraoperative SCC stimulation produced increases in autonomic sympathetic response that correlated with the salience of the behavioral responses. The autonomic changes were observed within seconds of initiating acute stimulation and prior to verbalization of subjective experiences. The probabilistic tractography analysis suggested that structural connectivity between the stimulated area and the midcingulate cortex is the primary pathway that mediates autonomic responsivity to SCC DBS.\n\n\nCONCLUSIONS\nThese findings demonstrate that acute SCC stimulation produces autonomic and behavioral changes in the operating room that are explained by the modulation of networks associated with long term antidepressant response. Intraoperative autonomic recordings paired with careful behavioral observations and precise anatomical mapping aid in the identification and classification of the intraoperative phenomena.