Comparative Effects of Three Novel Transcranial Electric Stimulation Protocols on Tremor and UPDRS-8 Scores

Transcranial electrical stimulation (tES) is a promising non-invasive therapeutic approach for Parkinson’s disease (PD), with the potential to modulate dysfunctional motor networks without the procedural risks associated with deep brain stimulation. This study compared the effects of three transcranial stimulation modalities on both motor and non-motor symptoms in PD. We conducted a randomized controlled study in which 26 patients with PD were assigned to one of three stimulation protocols: amplitude-modulated transcranial pulsed current stimulation (am-tPCS), multi-path spatial targeting with amplitude-modulated transcranial pulsed random noise stimulation (MP-am-tPRNS), or amplitude-modulated transcranial pulsed random noise stimulation (am-tPRNS). Stimulation was delivered bilaterally over the primary motor cortex and supplementary prefrontal regions through electrodes placed at C3/C4 and Fp1/Fp2 according to the international 10–20 system. Primary outcomes included changes in motor and cognitive function measured using the 8-Item Unified Parkinson’s Disease Rating Scale (UPDRS-8), along with quantitative tremor analysis derived from standardized 20–30-second video recordings. The results showed that am-tPCS was the only protocol to produce a statistically significant improvement in tremor amplitude, with a 4.6% reduction (p < 0.05). However, all three protocols improved overall UPDRS-8 scores. Specifically, am-tPRNS significantly improved non-motor subscale scores by 54.8% and overall UPDRS-8 scores by 20.3%, while the multi-path spatial targeting protocol significantly improved motor subscale scores by 29.5% (p < 0.05). At the individual level, tremor-band power reductions of up to 77% and UPDRS-8 improvements of up to 64% were observed, supporting the potential of amplitude-modulated tES as a meaningful intervention for PD motor symptoms. No adverse events were reported. These findings suggest that distinct tES modalities exert differential effects on motor and non-motor PD symptomatology. Future work will investigate a longer treatment period of 12 weeks to capture cumulative neuroplastic changes necessary for robust and sustained motor improvement.