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Anodal M1 tDCS Shapes Frequency-Specific Functional Connectivity and Network Topology in Parkinson's Disease.

Clara Simonetta,Matteo Conti,Jacopo Bissacco,Valerio Ferrari,C. Salimei,Federico Carparelli,Silvio Bagetta,D. Mascioli,Veronica Buttarazzi,Maria Mancini,F. Di Giuliano,N. Mercuri,M. Pierantozzi,Alessandro Stefani,T. Schirinzi

Published 2025 in Brain Stimulation

ABSTRACT

BACKGROUND Transcranial direct current stimulation (tDCS) is a promising non-invasive intervention for Parkinson's disease (PD), but its mechanisms of action remain unclear. Understanding its network-level effects may support its use as an adjunctive therapeutic option, particularly in intermediate-stage PD when symptoms begin to escape pharmacological control. OBJECTIVE To evaluate the clinical efficacy and functional connectivity (FC) changes of anodal tDCS over the primary motor cortex (M1) in patients with intermediate-stage PD. METHODS Twenty-five patients underwent a randomized, double-blind, sham-controlled, crossover protocol, receiving anodal and sham M1-tDCS. Clinical assessments were measured before and after each intervention, alongside high-density EEG (HD-EEG) recordings in the OFF-medication state. Band-specific FC was analyzed using network-based statistics (NBS), and network topology was examined through graph-theoretical measures. Thirty age-matched healthy controls were included for baseline comparisons. RESULTS anodal tDCS significantly reduced motor symptoms in the OFF-state, especially bradykinesia, tremor, and gait. It also improved non-motor symptoms and cognitive performance. HD-EEG FC analyses revealed increased α-band FC and decreased pathological β-band hyperconnectivity, both correlating with clinical improvements. Notably, graph analyses showed reduced scale-free organization in both α- and β-band networks post-tDCS, likely reflecting the widespread and non-selective stimulation of multiple nodes. Sham stimulation induced no significant changes. CONCLUSIONS Therapeutic effects of anodal M1-tDCS appear to be mediated by frequency-specific modulation of cortical networks, enhancing α-band synchronization and reducing β-band hypersynchrony, alongside a topological reconfiguration of brain architecture. These network-level effects strengthen the rationale for using tDCS in PD, particularly as a potential therapeutic option in the intermediate stage.

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