Neurophysiological effects of transcranial alternating current stimulation combined with multidisciplinary rehabilitation in Parkinson’s disease
Introduction Motor impairment in Parkinson’s disease (PD) often becomes inadequately controlled as the disease progresses. Rehabilitation therapy combined with noninvasive neuromodulation has shown benefits, yet the neural mechanisms underlying this remain unclear. This study aimed to identify neurophysiological and brain network features associated with motor improvement following high-intensity transcranial alternating current stimulation (Hi-tACS) combined with multidisciplinary intensive rehabilitation therapy (MIRT). Methods This secondary analysis was based on a randomized controlled trial (ChiCTR2300071969). Thirty patients receiving Hi-tACS combined with MIRT were included. Responders were defined as patients achieving a minimal clinically important difference improvement greater than 3.25 points on the Unified Parkinson’s Disease Rating Scale part III. Electroencephalographic spectral analysis, resting-state functional connectivity, and dynamic brain states assessed using hidden Markov modeling were performed. Partial correlation analyses were conducted for group-differentiating measures, controlling for age and disease duration. Results Compared with non-responders, responders showed increased temporal high beta frequencies relative power (95%CI 0.85(0.01–1.66), P = 0.047), reduced connectivity between the default mode and sensorimotor networks (95%CI -0.89(-1.71–0.05), P = 0.038), and decreased fractional occupancy of state 3 (95%CI 0.03(0.00–0.28), P = 0.033) and 6 (95%CI 0.02(0.00–0.35), P = 0.038). After Bonferroni correction, only changes in temporal high beta frequencies relative power were negatively correlated with changes in total UPDRS part III scores (R = -0.59, PBON = 0.012) and rigidity subscores (R = -0.74, PBON < 0.001). Discussion These results suggest that motor improvement following combined Hi-tACS and MIRT in PD patients is associated with alterations in brain oscillations and network connectivity, particularly in high-beta frequencies. The findings contribute to understanding the neural mechanisms underlying rehabilitation and neuromodulation in PD. Future studies should investigate the long-term effects of this intervention and its applicability in larger, more diverse populations. Moreover, exploring additional biomarkers may help identify individuals who are most likely to respond to this treatment. Clinical Trial Registration https://www.chictr.org.cn, identifer ChiCTR2300071969.