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The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n\u2009=\u200966) implanted bilaterally in globus pallidus internus (n\u2009=\u200934) or centromedial thalamus (n\u2009=\u200932) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate \u2018reverse\u2019 tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P\u2009=\u20090.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P\u2009&amp;lt;\u20090.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P\u2009=\u20090.012) and was robust to cross-validation. Regions in the anterior\/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P\u2009&amp;gt;\u20090.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P\u2009=\u20090.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.<\/jats:p>","DOI":"10.1093\/brain\/awaa188","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T15:10:56Z","timestamp":1590678656000},"page":"2607-2623","source":"Crossref","is-referenced-by-count":78,"title":["Structural connectivity predicts clinical outcomes of deep brain stimulation for Tourette syndrome"],"prefix":"10.1093","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6556-8957","authenticated-orcid":false,"given":"Kara A","family":"Johnson","sequence":"first","affiliation":[{"name":"Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-0294","authenticated-orcid":false,"given":"Gordon","family":"Duffley","sequence":"additional","affiliation":[{"name":"Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9093-7504","authenticated-orcid":false,"given":"Daria Nesterovich","family":"Anderson","sequence":"additional","affiliation":[{"name":"Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Neurosurgery, University of Utah, Salt Lake City, Utah, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill L","family":"Ostrem","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Welter","sequence":"additional","affiliation":[{"name":"Institut du Cerveau et de la Moelle Epiniere, Sorbonne Universit\u00e9s, University of Pierre and Marie Curie University of Paris, the French National Institute of Health and Medical Research U 1127, the National Center for Scientific Research 7225, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Baldermann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany"},{"name":"Department of Neurology, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany"},{"name":"Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Johanniter Hospital Oberhausen, EVKLN, Oberhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Huys","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Visser-Vandewalle","sequence":"additional","affiliation":[{"name":"Department of Stereotaxy and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Foltynie","sequence":"additional","affiliation":[{"name":"Functional Neurosurgery Unit, Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludvic","family":"Zrinzo","sequence":"additional","affiliation":[{"name":"Functional Neurosurgery Unit, Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Hariz","sequence":"additional","affiliation":[{"name":"Functional Neurosurgery Unit, Department of Clinical and Movement Neurosciences, University College London, Queen Square Institute of Neurology, London, UK"},{"name":"Department of Clinical Neuroscience, Umea University, Umea, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert F G","family":"Leentjens","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alon Y","family":"Mogilner","sequence":"additional","affiliation":[{"name":"Center for Neuromodulation, New York University Langone Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H","family":"Pourfar","sequence":"additional","affiliation":[{"name":"Center for Neuromodulation, New York University Langone Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Almeida","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases , Program for Movement Disorders and Neurorestoration, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7925-0747","authenticated-orcid":false,"given":"Aysegul","family":"Gunduz","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases , Program for Movement Disorders and Neurorestoration, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, USA"},{"name":"J Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly D","family":"Foote","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases , Program for Movement Disorders and Neurorestoration, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Okun","sequence":"additional","affiliation":[{"name":"Norman Fixel Institute for Neurological Diseases , Program for Movement Disorders and Neurorestoration, Departments of Neurology and Neurosurgery, University of Florida, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R","family":"Butson","sequence":"additional","affiliation":[{"name":"Scientific Computing and Imaging Institute, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah, USA"},{"name":"Department of Neurosurgery, University of Utah, Salt Lake City, Utah, USA"},{"name":"Departments of Neurology and Psychiatry, University of Utah, Salt Lake City, Utah, 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