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In Brain : a journal of neurology

Subcallosal cingulate deep brain stimulation (SCC-DBS) produces long-term clinical improvement in approximately half of patients with severe treatment-resistant depression (TRD). We hypothesized that both structural and functional brain attributes may be important in determining responsiveness to this therapy. In a TRD SCC-DBS cohort, we retrospectively examined baseline and longitudinal differences in MRI-derived brain volume (n = 65) and 18F-fluorodeoxyglucose-PET glucose metabolism (n = 21) between responders and non-responders. Support-vector machines (SVMs) were subsequently trained to classify patients' response status based on extracted baseline imaging features. A machine learning model incorporating pre-operative frontopolar, precentral/frontal opercular, and orbitofrontal local volume values classified binary response status (12 months) with 83% accuracy (leave-one-out cross-validation (LOOCV): 80% accuracy) and explained 32% of the variance in continuous clinical improvement. It was also predictive in an out-of-sample SCC-DBS cohort (n = 21) with differing primary indications (bipolar disorder/anorexia nervosa) (76% accuracy). Adding pre-operative glucose metabolism information from rostral anterior cingulate cortex and temporal pole improved model performance, enabling it to predict response status in the TRD cohort with 86% accuracy (LOOCV: 81% accuracy) and explain 67% of clinical variance. Response-related patterns of metabolic and structural post-DBS change were also observed, especially in anterior cingulate cortex and neighbouring white matter. Areas where responders differed from non-responders - both at baseline and longitudinally - largely overlapped with depression-implicated white matter tracts, namely uncinate fasciculus, cingulum bundle, and forceps minor/rostrum of corpus callosum. The extent of patient-specific engagement of these same tracts (according to electrode location and stimulation parameters) also served as a predictor of TRD response status (72% accuracy; LOOCV: 70% accuracy) and augmented performance of the volume-based (88% accuracy; LOOCV: 82% accuracy) and combined volume/metabolism-based SVMs (100% accuracy; LOOCV: 94% accuracy). Taken together, these results indicate that responders and non-responders to SCC-DBS exhibit differences in brain volume and metabolism, both pre- and post-surgery. Baseline imaging features moreover predict response to treatment (particularly when combined with information about local tract engagement) and could inform future patient selection and other clinical decisions.

Elias Gavin J B, Germann J├╝rgen, Boutet Alexandre, Pancholi Aditya, Beyn Michelle E, Bhatia Kartik, Neudorfer Clemens, Loh Aaron, Rizvi Sakina J, Bhat Venkat, Giacobbe Peter, Woodside D Blake, Kennedy Sidney H, Lozano Andres M


deep brain stimulation, depression, magnetic resonance imaging, positron emission tomography, subcallosal cingulate