{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:42Z","timestamp":1785403122587,"version":"3.56.0"},"posted":{"date-parts":[[2026,5,15]]},"group-title":"Neuroscience","reference-count":32,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["MR\/Z5050555\/1"],"award-info":[{"award-number":["MR\/Z5050555\/1"]}],"id":[{"id":"https:\/\/ror.org\/03x94j517","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Tourette syndrome (TS) is a neurodevelopmental disorder of childhood onset characterised by vocal and motor tics and is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction. TS often follows a developmental time course in which tics become increasingly more controlled during adolescence. However, many individuals continue to have debilitating tics into adulthood. This indicates that there may be important differences between adults with TS for whom the clinical phenotype is more stable, and children and adolescents with the disorder who may be undergoing developmental neuroplastic changes linked to the reduction of their tics.<\/jats:p>\n                <jats:p>Previous studies have used transcranial magnetic stimulation (TMS) to investigate changes in cortical motor excitability in individuals with TS, including measurement of resting motor threshold (RMT). However, the findings from these studies have been mixed, have varied between adult and child samples, and have often been based on small sample sizes. Here we report a multi-centre, mega-analytic, study in which RMT data collected from children and adults with TS at multiple research centres was pooled for analysis.<\/jats:p>\n                <jats:p>\n                  Results confirmed that mean RMT was significantly increased in individuals with TS compared to neurotypical controls. However, this result can be explained by the more important findings that: (a) RMT for adults with TS did not differ from that of neurotypical adults; and (b) the rate that RMT\n                  <jats:italic>decreases with age<\/jats:italic>\n                  during childhood and adolescence is reduced in individuals with TS compared to controls. Thus, while neurotypical individuals reach an adult RMT level by ~12-13 years of age, individuals with TS are substantially delayed in doing so, and do not reach an adult RMT level until much later, at ~24 years of age.\n                <\/jats:p>\n                <jats:p>We conclude therefore that differences in measures of cortical excitability between children and adolescents with TS and chronologically age-matched neurotypical controls may likely reflect a developmental delay in the maturation of functional brain networks in individuals with TS, which may normalise with age.<\/jats:p>","DOI":"10.64898\/2026.05.14.724875","type":"posted-content","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T08:35:16Z","timestamp":1778834116000},"source":"Crossref","is-referenced-by-count":0,"title":["Developmental delay in attaining adult levels of motor excitability in children and adolescents with Tourette syndrome: a mega-analysis study"],"prefix":"10.64898","author":[{"given":"Stephen R.","family":"Jackson","sequence":"first","affiliation":[{"name":"School of Psychology, University of Nottingham, UK"},{"name":"University of Nottingham Centre for Neuromodulation, Neurotechnology & Neurotherapeutics, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3208-2659","authenticated-orcid":false,"given":"Valerie","family":"Brandt","sequence":"additional","affiliation":[{"name":"Department of Psychology, Centre for Innovation in Mental Health, University of Southampton, UK"},{"name":"Clinic of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-9802","authenticated-orcid":false,"given":"Christine A.","family":"Conelea","sequence":"additional","affiliation":[{"name":"Department of Psychiatry & Behavioral Sciences, Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6921-9567","authenticated-orcid":false,"given":"Kevin J.","family":"Black","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry, Neurology, Radiology, and Neuroscience, Washington University in St. Louis, St. Louis, MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-6878","authenticated-orcid":false,"given":"Donald L.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-7194","authenticated-orcid":false,"given":"John","family":"Piacentini","sequence":"additional","affiliation":[{"name":"UCLA Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1367-6467","authenticated-orcid":false,"given":"John","family":"Rothwell","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology, University College London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5903-9370","authenticated-orcid":false,"given":"Yulia","family":"Worbe","sequence":"additional","affiliation":[{"name":"Paris Brain Institute - ICM, Sorbonne University, INSERM, CNRS Paris, France"},{"name":"Department of Clinical Neurophysiology, Assistance Publique des H\u00f4pitaux de Paris, H\u00f4pital Saint Antoine, 75012, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-6200","authenticated-orcid":false,"given":"Katherine","family":"Dyke","sequence":"additional","affiliation":[{"name":"School of Psychology, University of Nottingham, UK"},{"name":"University of Nottingham Centre for Neuromodulation, Neurotechnology & Neurotherapeutics, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052011101686000_2026.05.14.724875v2.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2012.11.013"},{"key":"2026052011101686000_2026.05.14.724875v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2006.01.001"},{"key":"2026052011101686000_2026.05.14.724875v2.3","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20044"},{"key":"2026052011101686000_2026.05.14.724875v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.12.009"},{"key":"2026052011101686000_2026.05.14.724875v2.5","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp299"},{"key":"2026052011101686000_2026.05.14.724875v2.6","doi-asserted-by":"publisher","DOI":"10.1177\/1073858415592594"},{"key":"2026052011101686000_2026.05.14.724875v2.7","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00575-3"},{"key":"2026052011101686000_2026.05.14.724875v2.8","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.154.9.1277"},{"key":"2026052011101686000_2026.05.14.724875v2.9","doi-asserted-by":"publisher","DOI":"10.1002\/mds.23418"},{"issue":"3","key":"2026052011101686000_2026.05.14.724875v2.10","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.brs.2011.04.001","article-title":"Altered neurophysiologic response to intermittent theta burst stimulation in Tourette syndrome","volume":"5","year":"2012","journal-title":"Brain stimulation"},{"issue":"6","key":"2026052011101686000_2026.05.14.724875v2.11","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1007\/s00702-007-0010-7","article-title":"Voluntary motor drive: possible reduction in Tourette syndrome","volume":"115","year":"2008","journal-title":"Journal of Neural Transmission"},{"key":"2026052011101686000_2026.05.14.724875v2.12","doi-asserted-by":"crossref","unstructured":"Brandt, V. , et al., Altered Synaptic Plasticity in Tourette\u2019s Syndrome and Its Relationship to Motor Skill Learning. 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