• Kara A Johnson, P Thomas Fletcher, Domenico Servello, Alberto Bona, Mauro Porta, Jill L Ostrem, Eric Bardinet, Marie-Laure Welter, Andres M Lozano, Juan Carlos Baldermann, Jens Kuhn, Daniel Huys, Thomas Foltynie, Marwan Hariz, Eileen M Joyce, Ludvic Zrinzo, Zinovia Kefalopoulou, Jian-Guo Zhang, Fan-Gang Meng, ChenCheng Zhang, Zhipei Ling, Xin Xu, Xinguang Yu, Anouk Yjm Smeets, Linda Ackermans, Veerle Visser-Vandewalle, Alon Y Mogilner, Michael H Pourfar, Leonardo Almeida, Aysegul Gunduz, Wei Hu, Kelly D Foote, Michael S Okun, and Christopher R Butson.
• Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA.
• J. Neurol. Neurosurg. Psychiatr. 2019 Oct 1; 90 (10): 1078-1090.

BackgroundDeep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting.MethodsWe collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases.ResultsTics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi.ConclusionThe results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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