Time-Varying Effective Network of Rehabilitation in Parkinson's Disease With Disease Laterality: A TMS-EEG Study

Parkinson's disease (PD) is predominantly characterized by unilateral motor manifestations and heterogeneous treatment responses. Combining single-pulse transcranial magnetic stimulation with electroencephalography (TMS-EEG) enables sensitive detection of cortical plasticity and dynamic brain network pathophysiology.

To elucidate the neural mechanisms underlying rehabilitation effects in PD, 27 left-affected (LPD) and 27 right-affected (RPD) patients were enrolled based on concordant lateralization between initial motor-symptom onset and current motor asymmetry quantified from the Movement Disorders Society-Sponsored Revised Unified Parkinson's Disease Rating Scale Part III limb subitems. All participants received a 2-week multidisciplinary intensive rehabilitation therapy (MIRT). By integrating single-pulse TMS-EEG recordings with adaptive directed transfer function analysis, this study evaluated network alterations within the primary motor cortex and posterior parietal cortex before and after MIRT. Furthermore, correlations between neural network changes and clinical functional improvements were examined.

Significant alterations in brain network connectivity emerged, most notably 100 ms post-TMS of the posterior parietal cortex in the affected hemisphere. In LPD patients, decreased connectivity from the right central region to the parietal cortex correlated with improvements in axial symptoms, while increased outflow from the bilateral temporal lobes was associated with cognitive enhancement. Conversely, in RPD patients, decreased whole-brain transfer efficiency correlated with improved motor function, and changes in outflow from the left occipital and medial frontal lobes were associated with cognitive enhancement.

The distinct modulatory effects of MIRT on the brain networks of LPD and RPD patients provide lateralized mechanistic insights into rehabilitation-related neural mechanisms in PD, potentially guiding the development of personalized and optimized therapeutic strategies.