• Juan Carlos Baldermann, Corina Melzer, Alexandra Zapf, Sina Kohl, Lars Timmermann, Marc Tittgemeyer, Daniel Huys, Veerle Visser-Vandewalle, Andrea A Kühn, Andreas Horn, and Jens Kuhn.
• Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany. Electronic address: juan.baldermann@uk-koeln.de.
• Biol. Psychiatry. 2019 May 1; 85 (9): 735-743.

BackgroundDeep brain stimulation for obsessive-compulsive disorder is a rapidly developing treatment strategy for treatment-refractory patients. Both the exact target and impact on distributed brain networks remain a matter of debate. Here, we investigated which regions connected to stimulation sites contribute to clinical improvement effects and whether connectivity is able to predict outcomes.MethodsWe analyzed 22 patients (13 female) with treatment-refractory obsessive-compulsive disorder undergoing deep brain stimulation targeting the anterior limb of the internal capsule/nucleus accumbens. We calculated stimulation-dependent optimal connectivity separately for patient-specific connectivity data of 10 patients and for 12 additional patients using normative connectivity. Models of optimal connectivity were subsequently used to predict outcome in both an out-of-sample cross-validation and a leave-one-out cross-validation across the whole group.ResultsThe resulting models successfully cross-predicted clinical outcomes of the respective other sample, and a leave-one-out cross-validation across the whole group further demonstrated robustness of our findings (r = .630, p < .001). Specifically, the degree of connectivity between stimulation sites and medial and lateral prefrontal cortices significantly predicted clinical improvement. Finally, we delineated a frontothalamic pathway that is crucial to be modulated for beneficial outcome.ConclusionsSpecific connectivity profiles, encompassing frontothalamic streamlines, can predict clinical outcome of deep brain stimulation for obsessive-compulsive disorder. After further validation, our findings may be used to guide both deep brain stimulation targeting and programming and to inform noninvasive neuromodulation targets for obsessive-compulsive disorder.Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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