In a double-blind randomized trial (STEP-PD), adding bilateral M1 intermittent theta-burst stimulation to a two-week intensive physical therapy program produced a modest but statistically significant acute improvement in OFF-state MDS-UPDRS III (Δ = -4.60, p = 0.034) with exploratory gains in gait…

Provides a readily translatable, nonpharmacologic cortical-priming approach with objective EEG biomarkers that can enhance short-term rehabilitation outcomes in PD and serve as a platform for optimizing neuromodulation parameters and studying sustained clinical effects.

Physical therapy (PT) is commonly used to alleviate specific symptoms of Parkinson's disease (PD). Its efficacy may be enhanced by cortical priming, which aims to improve the brain's responsiveness to rehabilitation. This randomized, double-blind, sham-controlled trial-Stimulation to Enhance Physical Therapy in Parkinson's Disease (STEP-PD)-investigated whether combining PT with intermittent theta-burst stimulation (iTBS) applied over the primary motor cortex (M1-iTBS) could provide additional gains in motor function in patients with PD. Fifty participants with PD received PT combined with either bilateral M1-iTBS or sham-iTBS, twice daily, five days per week for two weeks. The primary outcome was the change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III) in the OFF-medication state, assessed at baseline and immediately post-intervention. Secondary outcomes included the Parkinson's Disease Questionnaire-39 (PDQ-39), and exploratory outcomes included clinical and instrumented assessments of gait and balance, as well as electroencephalography (EEG)-based measures of functional connectivity. Patients receiving PT combined with M1-iTBS showed greater acute improvement in OFF-state MDS-UPDRS III scores compared to those receiving sham stimulation (Δ = -4.60, p = 0.034). There were no significant differences in PDQ-39 scores. Exploratory analyses revealed improved gait stability, fewer falls, and reduced beta-band synchronization on resting-state EEG, suggesting that M1-iTBS may modulate motor networks to facilitate functional recovery. These findings suggest that combining PT with M1-iTBS has promise as an acute cortical priming approach to improve the short-term efficacy of PD rehabilitation, although further research is required to determine the sustainability of these effects.