{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T18:32:15Z","timestamp":1791484335971,"version":"4.3.4"},"posted":{"date-parts":[[2026,2,23]]},"group-title":"Neurology","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our analyses identified tic response targets that followed the course of known structural projections interconnecting pallidum and thalamus.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.21.26346772","type":"posted-content","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T01:20:26Z","timestamp":1771896026000},"source":"Crossref","is-referenced-by-count":2,"title":["Optimal Deep Brain Stimulation Locations for Gilles de la Tourette Syndrome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9951-374X","authenticated-orcid":false,"given":"Ilkem Aysu","family":"Sahin","sequence":"first","affiliation":[{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin 10117, Germany"},{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantin","family":"Butenko","sequence":"additional","affiliation":[{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"},{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA; Department of Neurology, University of Florida, Gainesville, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Friedrich","sequence":"additional","affiliation":[{"name":"Institute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany"},{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"},{"name":"Julius-Maximilian-University Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sim\u00f3n","family":"Oxenford","sequence":"additional","affiliation":[{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3315-3591","authenticated-orcid":false,"given":"Ningfei","family":"Li","sequence":"additional","affiliation":[{"name":"Institute for Network Stimulation, Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, Cologne, Germany"},{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"},{"name":"Northwestern Polytechnical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Zvarova","sequence":"additional","affiliation":[{"name":"Einstein Center for Neurosciences Berlin, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Berlin 10117, Germany"},{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Hollunder","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanditha","family":"Rajamani","sequence":"additional","affiliation":[{"name":"Center for Brain Circuit Therapeutics, 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L.","family":"Goede","sequence":"additional","affiliation":[{"name":"Movement Disorders and Neuromodulation Unit, Department of Neurology with Experimental Neurology, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin 10117, Germany"},{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Mass General Brigham, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Tietze","sequence":"additional","affiliation":[{"name":"Institute of Neuroradiology, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health (BIH), Berlin, 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Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Andrade","sequence":"additional","affiliation":[{"name":"Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabea","family":"Schmahl","sequence":"additional","affiliation":[{"name":"Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Heiden","sequence":"additional","affiliation":[{"name":"Department of Stereotactic and Functional Neurosurgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, 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