{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:20:27Z","timestamp":1766578827256,"version":"build-2065373602"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:00:00Z","timestamp":1700870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","award":["18H05523","19H01091","B203060001"],"award-info":[{"award-number":["18H05523","19H01091","B203060001"]}]},{"name":"Communications R&amp;D Promotion Programme from the Ministry of Internal Affairs and Communications, Japan","award":["18H05523","19H01091","B203060001"],"award-info":[{"award-number":["18H05523","19H01091","B203060001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Aim: To elucidate the pathophysiology of Gilles de la Tourette syndrome (GTS), which is associated with prior use of dopamine receptor antagonists (blockers) and treatment by L-Dopa, through saccade performance. Method: In 226 male GTS patients (5\u201314 years), we followed vocal and motor tics and obsessive\u2013compulsive disorder (OCD) after discontinuing blockers at the first visit starting with low-dose L-Dopa. We recorded visual- (VGS) and memory-guided saccades (MGS) in 110 patients and 26 normal participants. Results: At the first visit, prior blocker users exhibited more severe vocal tics and OCD, but not motor tics, which persisted during follow-up. Patients treated with L-Dopa showed greater improvement of motor tics, but not vocal tics and OCD. Patients with and without blocker use showed similarly impaired MGS performance, while patients with blocker use showed more prominently impaired inhibitory control of saccades, associated with vocal tics and OCD. Discussion: Impaired MGS performance suggested a mild hypodopaminergic state causing reduced direct pathway activity in the (oculo-)motor loops of the basal ganglia\u2013thalamocortical circuit. Blocker use may aggravate vocal tics and OCD due to disinhibition within the associative and limbic loops. The findings provide a rationale for discouraging blocker use and using low-dose L-Dopa in GTS.<\/jats:p>","DOI":"10.3390\/brainsci13121634","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:32:03Z","timestamp":1701055923000},"page":"1634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Pathophysiology of Gilles de la Tourette Syndrome: Changes in Saccade Performance by Low-Dose L-Dopa and Dopamine Receptor Blockers"],"prefix":"10.3390","volume":"13","author":[{"given":"Yasuo","family":"Terao","sequence":"first","affiliation":[{"name":"Department of Medical Physiology, Kyorin University, Tokyo 181-8611, Japan"},{"name":"Department of Neurology, University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiko","family":"Nomura","sequence":"additional","affiliation":[{"name":"Yoshiko Nomura Neurological Clinic for Children, Tokyo 113-0034, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Segawa Memorial Neurological Clinic for Children, Tokyo 101-0062, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okihide","family":"Hikosaka","sequence":"additional","affiliation":[{"name":"Section of Neuronal Networks, Laboratory of Sensorimotor Research, National Eye Institute, Bethesda, MD 20892-2510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-1683","authenticated-orcid":false,"given":"Kazue","family":"Kimura","sequence":"additional","affiliation":[{"name":"Segawa Memorial Neurological Clinic for Children, Tokyo 101-0062, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun-ichi","family":"Matsuda","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Yugeta","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1579-8807","authenticated-orcid":false,"given":"Francesco","family":"Fisicaro","sequence":"additional","affiliation":[{"name":"Department of Human Neurophysiology, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6659-7485","authenticated-orcid":false,"given":"Kyoko","family":"Hoshino","sequence":"additional","affiliation":[{"name":"Segawa Memorial Neurological Clinic for Children, Tokyo 101-0062, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshikazu","family":"Ugawa","sequence":"additional","affiliation":[{"name":"Department of Human Neurophysiology, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.tins.2006.01.001","article-title":"Recent advances in Tourette syndrome research","volume":"29","author":"Albin","year":"2006","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"12387","DOI":"10.1523\/JNEUROSCI.0150-11.2011","article-title":"Neurobiology of Tourette syndrome: Current status and need for further investigation","volume":"31","author":"Felling","year":"2011","journal-title":"J. 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