Evidence map›Paper›PMID 41810380›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Optimal Deep Brain Stimulation Locations for Gilles de la Tourette Syndrome.

Ilkem Aysu Sahin, Konstantin Butenko, Kara A Johnson, Helen Friedrich, Simón Oxenford, Ningfei Li, Patricia Zvarova, Barbara Hollunder, Nanditha Rajamani, Garance M Meyer and 52 more

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Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

62 authors.

Ilkem Aysu SahinEinstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.ORCID 0009-0005-9951-374X
Konstantin ButenkoMovement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany.
Kara A JohnsonDepartment of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA.
Helen FriedrichInstitute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.
Simón OxenfordMovement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany.
Ningfei LiInstitute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.ORCID 0000-0003-3315-3591
Patricia ZvarovaEinstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.
Barbara HollunderCenter for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
Nanditha RajamaniCenter for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
Garance M MeyerCenter for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA.
Clemens NeudorferDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Maike MustinInstitute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.
Lukas L GoedeMovement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin 10117, Germany.
Anna TietzeInstitute of Neuroradiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
Wolf-Julian NeumannEinstein Center for Neurosciences Berlin, Charité - Universitätsmedizin Berlin, Berlin 10117, Germany.ORCID 0000-0002-6758-9708
Juan Carlos BaldermannDepartment of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Till DembekUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.ORCID 0000-0001-7023-146X
Christina van der LindenUniversity of Cologne, Faculty of Medicine and University Hospital Cologne, Department of Neurology, Cologne, Germany.ORCID 0000-0003-2091-4638
Anna C von OlbergInstitute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.
Jens KuhnDepartment of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Daniel HuysDepartment of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Pablo AndradeDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Rabea SchmahlDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Petra HeidenDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Yulia WorbeSorbonne University, Inserm U1127, CNRS UMR7225, UM75, Paris Brain Institute, Movement Investigation and Therapeutics Team, 75013 Paris, France.
Nadya PyatigorskayaSorbonne University, Paris Brain Institute - ICM, Inserm, CNRS, Department of Radiology, Hôpital de la Pitié Salpêtrière (DMU 6), AP-HP, 75013, Paris, France.
Carine KarachiInserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Paris Brain Institute, Paris, France.
Marie-Laure WelterInserm 1127, Sorbonne Université, UPMC Univ Paris 06, UMRS 1127, CNRS, UMR 7225, Paris Brain Institute, Paris, France.
Linda AckermansDepartment of Neurosurgery, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
Anouk Y J M SmeetsDepartment of Neurosurgery, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
Albert F G LeentjensDepartment of Psychiatry, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
Chencheng ZhangDepartment of Neurosurgery, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Bomin SunDepartment of Neurosurgery, Rujin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jian-Guo ZhangBeijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Fan-Gang MengBeijing Neurosurgical Institute, Capital Medical University, Beijing, China.
Xinguang YuDepartment of Neurosurgery, Chinese PLA General Hospital, Beijing, 100853, China.
Xin XuDepartment of Neurosurgery, Chinese PLA General Hospital, Beijing, 100853, China.
Zhipei LingDepartment of Neurosurgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan, 572000, China.
Domenico ServelloNeurosurgical Department, IRCCS Istituto Ortopedico Galeazzi, Milan, Lombardia, Italy.
Alberto BonaNeurosurgical Department, IRCCS Istituto Ortopedico Galeazzi, Milan, Lombardia, Italy.
Mauro PortaTourette's Syndrome and Movement Disorders Center, IRCCS Istituto Ortopedico Galeazzi, Milan, Lombardia, Italy.
Alon Y MogilnerCenter for Neuromodulation, Departments of Neurology and Neurosurgery, New York University Medical Center, New York, New York, USA.
Michael H PourfarCenter for Neuromodulation, Departments of Neurology and Neurosurgery, New York University Medical Center, New York, New York, USA.
Jill L OstremDepartment of Neurology, University of California San Francisco, San Francisco, California, USA.
Thomas FoltynieDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Patricia LimousinDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Ludvic ZrinzoDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Eileen M JoyceDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Zinovia KefalopoulouDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Alida A PostmaDepartment of Radiology and Nuclear Medicine, Maastricht University Medical Center, the Netherlands.
Luigi M RomitoParkinson and Movement Disorders Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.ORCID 0000-0002-6772-1035
Matteo VissaniDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-3908-7620
Alberto MazzoniThe BioRobotics Institute, Scuola Superiore Sant'Anna, Pisa, Italy.
Osvaldo Vilela-FilhoDivision of Neurosurgery, Department of Surgery, Medical School, Federal University of Goiás, Goiânia, Brazil.
Andres M LozanoDivision of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Martin ParentCERVO Brain Research Centre, Quebec City, Quebec, Canada.
Abbas F SadikotDepartment of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University Health Centre, McGill University, Montreal, QC, Canada.
Kelly D FooteDepartment of Neurosurgery, Shands at University of Florida, University of Florida, Gainesville.
Christopher R ButsonDepartment of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-2319-1263
Veerle Visser-VandewalleDepartment of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Michael S OkunDepartment of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA.
Andreas HornInstitute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany.

Funding

BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC)UM1NS132358 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI Suzanne N Haber, Elizabeth M. C. Hillman · 2023 to 2026
$17.5M
Using human brain connectivity to identify the causal neuroanatomical substrate of depression symptomsR01MH113929 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2017 to 2026
$6.9M
Defining Targets for Tic Detection and Suppression in Tourette Syndrome Deep Brain StimulationUH3NS119844 · NINDS · UNIVERSITY OF FLORIDA · PI BUTSON, CHRISTOPHER R, GUNDUZ, AYSEGUL · 2021 to 2025
$5.0M
Web-based Automated Imaging Differentiation of ParkinsonismU01NS119562 · NINDS · UNIVERSITY OF FLORIDA · PI BARMPOUTIS, ANGELOS, OKUN, MICHAEL S · 2021 to 2025
$4.8M
Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive DisorderR01MH130666 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.9M
Using Brain Lesions and Deep Brain Stimulation to Identify an Epilepsy CircuitR01NS127892 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL D FOX · 2022 to 2026
$3.4M
Mobile Decision Support System for Nurse Management of Neuromodulation TherapyR01NR014852 · NINR · UNIVERSITY OF UTAH · PI BUTSON, CHRISTOPHER R, OKUN, MICHAEL S · 2015 to 2019
$2.9M
THE HUMAN THALAMOCORTICAL NETWORK IN TOURETTE SYNDROMER01NS096008 · NINDS · UNIVERSITY OF FLORIDA · PI GUNDUZ, AYSEGUL, OKUN, MICHAEL S · 2016 to 2020
$1.8M
University of Florida R25 Early Research Program for Neurology and Neurosurgery ResidentsR25NS108939 · NINDS · UNIVERSITY OF FLORIDA · PI HOH, BRIAN LIM, HOH, BRIAN LIM · 2019 to 2024
$537k
Basal Ganglia Network Neurophysiology of Depression in Parkinson’s DiseaseK99NS137249 · NINDS · UNIVERSITY OF FLORIDA · PI JOHNSON, KARA ANN · 2025 to 2025
$112k
NIMH NIH HHS R01 MH113929NIMH NIH HHS R01 MH130666NINDS NIH HHS K99 NS137249NINDS NIH HHS R01 NS096008NINDS NIH HHS R01 NS127892NINDS NIH HHS R25 NS108939NINDS NIH HHS U01 NS119562NINDS NIH HHS UH3 NS119844NINDS NIH HHS UM1 NS132358NINR NIH HHS R01 NR014852
6 · The paper itself

Abstract

Background: Deep brain stimulation has emerged as an effective investigational treatment for select cases of severe Gilles de la Tourette Syndrome. Defining the optimal stimulation sites within different targets and the specific tic improvement network across targets will be important to guide neuromodulation therapies. Methods: This retrospective multi-center cohort study analyzed stimulation locations in patients who received bilateral deep brain stimulation for Gilles de la Tourette Syndrome across 12 centers world-wide. The brain targets included the thalamus (n=43), pallidum (n=56) and subthalamic nucleus (n=16). The median follow-up period was 6 months. Imaging data were processed using a dedicated pipeline and a recently introduced voxel-wise sweetspot mapping technique. Since tic response landscapes visually resembled streamline tract connections, we carried out extensive anatomical delineations of pallidothalamic and thalamostriatal fibers. This anatomical information was used to interpret sweetspot landscapes across the three target regions. Results: Tic response maps revealed three tic-response peaks in both thalamus and pallidum. Based on thalamic and pallidal response maps, outcomes in the subthalamic DBS cohort, stimulated between the two other targets, could be explained (R=0.58, p=0.019). Across the three targets, response maps followed the anatomical course of three bundles. Namely, specific subregions of the ansa lenticularis, the fasciculus lenticularis, and projections from the posterior intralaminar thalamic nuclei to the lentiform nucleus. Stimulation overlaps with these bundles explained 19% of the variance in tic improvement across the three targets. Response maps could explain variance in an independent test cohort (n=8, R=0.70, p=0.026). Response maps were also calculated for obsessive compulsive behavior, which revealed similarities to the tic response sites in pallidum but clearly distinct results and generally less efficacy in the thalamus. Conclusion: Our analyses identified tic response targets that followed the course of known structural projections interconnecting pallidum and thalamus.

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PMID41810380
PMCPMC12970366

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