1 3 Exp Brain Res (2017) 235:841–850 DOI 10.1007/s00221-016-4847-6 RESEARCH ARTICLE BDNF and LTP-/LTD-like plasticity of the primary motor cortex in Gilles de la Tourette syndrome L. Marsili 1 · A. Suppa 1,2 · F. Di Stasio 2 · D. Belvisi 2 · N. Upadhyay 1 · I. Berardelli 1 · M. Pasquini 1 · S. Petrucci 1,3 · M. Ginevrino 3,4 · G. Fabbrini 1,2 · F. Cardona 5 · G. Defazio 6 · A. Berardelli 1,2 Received: 29 July 2016 / Accepted: 24 November 2016 / Published online: 30 November 2016 © Springer-Verlag Berlin Heidelberg 2016 according to BDNF polymorphism (Val/Val vs Met car- riers) in patients and controls. Fourteen healthy subjects and 13 GTS patients were Met carriers. When considering the whole group of controls, as expected, iTBS increased whereas cTBS decreased MEPs. Differently, iTBS/cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS. When comparing responses to TBS according to BDNF polymorphism, in healthy subjects, Met carri- ers showed reduced MEP changes compared with Val/Val individuals. Conversely, in patients with GTS, responses to iTBS/cTBS were comparable in Val/Val individuals and Met carriers. YGTSS and Y-BOCS scores were comparable in Met carriers and in Val/Val subjects. We conclude that iTBS and cTBS failed to induce LTP-/LTD-like plasticity in patients with GTS, and this was not affected by BDNF genotype. Keywords Tourette syndrome · Brain-derived neurotrophic factor · Primary motor cortex · Cortical plasticity · Theta-burst stimulation Abbreviations GTS Gilles de la Tourette syndrome OCD Obsessive–compulsive disorder M1 Primary motor cortex TBS Theta-burst stimulation iTBS Intermittent theta-burst stimulation cTBS Continuous theta-burst stimulation PAS Paired associative stimulation LTP Long-term potentiation LTD Long-term depression MEP Motor-evoked potential HS Healthy subjects BDNF Brain-derived neurotrophic factor Val Valine Abstract Gilles de la Tourette syndrome (GTS) is charac- terized by motor and vocal tics and often associated with obsessive–compulsive disorder (OCD). Responses to inter- mittent/continuous theta-burst stimulation (iTBS/cTBS), which probe long-term potentiation (LTP)-/depression (LTD)-like plasticity in the primary motor cortex (M1), are reduced in GTS. ITBS-/cTBS-induced M1 plasticity can be affected by brain-derived neurotrophic factor (BDNF) polymorphism. We investigated whether the BDNF poly- morphism influences iTBS-/cTBS-induced LTP-/LTD-like M1 plasticity in 50 GTS patients and in 50 age- and sex- matched healthy subjects. In GTS patients, motor and psy- chiatric (OCD) symptom severity was rated using the Yale Global Tic Severity Scale (YGTSS) and the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS). We compared M1 iTBS-/cTBS-induced plasticity in healthy subjects and in patients with GTS. We also compared responses to TBS L. Marsili and A. Suppa have contributed equally to the manuscript. * A. Berardelli alfredo.berardelli@uniroma1.it 1 Department of Neurology and Psychiatry, “Sapienza” University of Rome, Rome, Italy 2 IRCCS Neuromed Institute, Pozzilli, IS, Italy 3 Neurogenetics Unit, IRCCS Santa Lucia Foundation, Rome, Italy 4 Department of Molecular Medicine, University of Pavia, Pavia, Italy 5 Department of Pediatrics and Child Neuropsychiatry, “Sapienza” University of Rome, Rome, Italy 6 Department of Neurological and Psychiatric Sciences, University of Bari, Bari, Italy