RT journal article T1 Bilateral intermittent theta burst stimulation over the primary motor cortex improves motor and affective symptoms via thalamic network reintegration in mid-stage Parkinson's disease A1 Macias García, Paloma A1 Rashid Abdu Rahim López, Raúl A1 Cruz Gómez, Álvaro Javier A1 Sánchez Fernández, Francisco Luis A1 Sarrias Arrabal, Esteban A1 Cano Cano, Fátima A1 Lozano Soto, Elena María A1 Sanmartino, Florencia Soledad A1 Espinosa Rosso, Raúl A1 González Rosa, Javier Jesús A2 Psicología K1 Functional connectivity K1 Intermittent theta burst stimulation K1 Parkinson's disease K1 Motor and nonmotor symptoms K1 Resting-state functional magnetic K1 neuroimaging AB Bilateral intermittent theta burst stimulation (iTBS) targeting the primary motor cortex (M1) has emerged as a promising neuromodulatory approach for Parkinson's disease (PD), although evidence supporting its clinical efficacy as an adjunctive treatment remains limited. This randomized, double-blind, sham-controlled crossover study examined the therapeutic potential of bilateral M1-iTBS in fifteen patients with mid-stage PD in the on-medication state. Motor, neuropsychiatric, and cognitive outcomes were assessed through standardized clinical scales following five iTBS sessions, alongside voxelwise resting-state functional magnetic resonance imaging, to identify neural-related mechanisms. Real iTBS induced a maximum improvement of nine points on the Movement Disorder Society-Unified PD Rating Scale part III, with clinical responders (≥20% improvement) demonstrating an eleven-point enhancement. Responders exhibited strengthened cerebello-thalamic and thalamo-cortical connectivity, suggesting partial thalamic functional reintegration with associative cortices and compensatory functional reorganization, which correlated significantly with reduced bradykinesia. Additionally, real iTBS produced clinically meaningful improvement in affective symptomatology in depression and anxiety responder patients, accompanied by modulation of top-down and bottom-up emotion regulation circuits and normalization of cerebellar activity. These findings support bilateral M1-iTBS as an effective adjunctive intervention for managing motor and nonmotor manifestations in patients with mid-stage PD, with mechanistic insights provided by symptom-related functional connectivity changes. PB Elsevier SN 1933-7213 YR 2026 FD 2026-04-01 LK http://hdl.handle.net/10498/40389 UL http://hdl.handle.net/10498/40389 LA eng DS Repositorio Institucional de la Universidad de Cádiz RD 06-nov-2026