Phd in CLINICAL EXPERIMENTAL NEUROSCIENCE AND PSYCHIATRY

Thesis title: Meccanismi corticali dell’esecuzione e dell’inibizione dei tic nella sindrome di Gilles de la Tourette: uno studio di TMS-EEG

Tics, the core feature of Gilles de la Tourette syndrome (GTS), are repetitive movements or vocalizations often preceded by premonitory urges (PU). Tic expression and suppression rely on the interaction between fronto-parietal (FPN) and sensorimotor (SMN) networks, involving regions such as the dorsolateral prefrontal cortex (DLPFC), inferior parietal lobule (IPL), supplementary motor area (SMA) and primary motor cortex (M1). Transcranial magnetic stimulation combined with EEG (TMS-EEG) enables direct assessment of cortical excitability and connectivity within these networks. This study investigated how voluntary tic suppression modulates cortical reactivity in GTS by analyzing TMS-evoked potentials (TEPs) and TMS-related spectral perturbations (TRSPs) elicited from FPN (DLPFC, IPL) and SMN (SMA, M1) regions. We studied 28 adult GTS patients and 30 age-matched healthy controls using TMS-EEG to assess cortical reactivity in the DLPFC, IPL, SMA, and M1 during free tic expression and voluntary suppression. EEG and EMG signals were recorded under controlled conditions, and TMS-evoked potentials (TEPs) and TMS-related spectral perturbations (TRSPs) were extracted following rigorous preprocessing. Statistical analyses compared conditions and groups and explored correlations between neurophysiological measures and clinical features including tic severity, premonitory urges and comorbidities. We found that GTS patients exhibit selective alterations in cortical reactivity within the fronto-premotor network. During free tic expression, GTS patients showed reduced DLPFC reactivity (smaller P60 TEP) but preserved motor (M1, SMA) responses, suggesting diminished prefrontal control rather than primary motor hyperexcitability. During voluntary suppression, healthy controls increased SMA excitability and broadly modulated oscillatory activity across motor regions, whereas GTS patients displayed reduced SMA engagement and abnormal DLPFC low-β modulation, reflecting inefficient or rigid inhibitory control. Comorbid OCD amplified prefrontal θ/α suppression, indicating greater cognitive effort, while medication partially normalized early DLPFC responses. Overall, our findings reveal a network-level imbalance characterized by impaired DLPFC–SMA coordination and state-dependent suppression deficits, highlighting a potential target for future neuromodulatory interventions aimed at strengthening prefrontal–premotor regulation in GTS.