Objective:

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) in Parkinson's disease patients.

Approach:

• Study Design: Secondary analysis of a randomized controlled trial (ChiCTR2300071969) involving 30 patients receiving Hi-tACS combined with MIRT.
• Assessment Methods: Electroencephalographic spectral analysis, resting-state functional connectivity, and dynamic brain states assessed using hidden Markov modeling.
• Statistical Analysis: Partial correlation analyses controlling for age and disease duration.

Key Findings:

• 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).
• Decreased fractional occupancy of specific brain states (95%CI 0.03(0.00–0.28), P = 0.033 and 95%CI 0.02(0.00–0.35), P = 0.038).
• 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).

Interpretation:

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.

Limitations:

• The study's findings are based on a small sample size of 30 patients.
• The lack of significant group-level differences between active and sham interventions indicates variability in clinical response.

Conclusion:

The findings contribute to understanding the neural mechanisms underlying rehabilitation and neuromodulation in PD.

Sources:

• Clinical Trial Registration