Anodal M1 tDCS shapes frequency-specific functional connectivity and network topology in Parkinson's disease

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