Neurobiological after-effects and clinical efficacy of transcranial magnetic stimulation (TMS) in Parkinson's disease: a systematic review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, deeply affecting quality of life. While pharmacological and surgical treatments like levodopa and deep brain stimulation (DBS) are standard, limitations in long-term efficacy and accessibility have led to growing interest in non-invasive neuromodulatory approaches such as transcranial magnetic stimulation (TMS). This systematic review aims to critically appraise the evidence on the clinical efficacy and neurobiological effects of TMS in PD, encompassing motor and non-motor symptom modulation, neurophysiological biomarkers, and neuroimaging findings. Following PRISMA-ScR guidelines, literature was searched in MEDLINE, EMBASE, and Scopus. Fifty eligible clinical studies were analyzed, with 28 directly addressing TMS effects on PD through clinical, neurophysiological, or imaging outcomes. High-frequency repetitive TMS (rTMS) over the primary motor cortex (M1) shows moderate efficacy in improving bradykinesia and rigidity. Stimulation of supplementary motor area (SMA) and dorsolateral prefrontal cortex (DLPFC) yielded variable effects on gait and mood. Neurophysiological studies consistently report alterations in intracortical excitability (e.g., reduced SICI, shortened CSP), partially restored by TMS and modulated by medication or DBS. Imaging studies revealed changes in functional connectivity and dopamine release post-TMS. Notably, the clinical state ("on" vs. "off" medication), stimulation parameters, and methodological heterogeneity significantly influenced outcomes. TMS represents a promising adjunctive therapy in PD, with evidence supporting its modulatory role on cortical excitability and potential clinical benefit. However, heterogeneity in protocols, small sample sizes, and placebo effects limit definitive conclusions. Future research should prioritize standardized methodologies, exploration of optimal stimulation parameters, identification of predictive biomarkers, and integration with rehabilitative strategies to personalize treatment. Rigorous, sham-controlled trials with long-term follow-up are essential to establish TMS as a reliable therapeutic tool in PD management.