Characterizing cortical responses to short-term multidisciplinary intensive rehabilitation treatment in patients with Parkinson's disease: A transcranial magnetic stimulation and electroencephalography study

Abstract

Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) is a powerful non-invasive tool for qualifying the neurophysiological effects of interventions by recording TMS-induced cortical activation with high temporal resolution and generates reproducible and reliable waves of activity without participant cooperation. Cortical dysfunction contributes to the pathogenesis of the clinical symptoms of Parkinson's disease (PD). Here, we examined changes in cortical activity in patients with PD following multidisciplinary intensive rehabilitation treatment (MIRT). Forty-eight patients with PD received 2 weeks of MIRT. The cortical response was examined following single-pulse TMS over the primary motor cortex by 64-channel EEG, and clinical symptoms were assessed before and after MIRT. TMS-evoked potentials were quantified by the global mean field power, as well as oscillatory power in theta, alpha, beta, and gamma bands, and their clinical correlations were calculated. After MIRT, motor and non-motor symptoms improved in 22 responders, and only non-motor function was enhanced in 26 non-responders. Primary motor cortex stimulation reduced global mean field power amplitudes in responders but not significantly in non-responders. Oscillations exhibited attenuated power in the theta, beta, and gamma bands in responders but only reduced gamma power in non-responders. Associations were observed between beta oscillations and motor function and between gamma oscillations and non-motor symptoms. Our results suggest that motor function enhancement by MIRT may be due to beta oscillatory power modulation and that alterations in cortical plasticity in the primary motor cortex contribute to PD recovery.

Keywords: MIRT; PD; TMS-EEG; beta oscillation; primary motor cortex.

FIGURE 1

Workflow of the Parkinson’s disease (PD) treatment design and transcranial magnetic stimulation and electroencephalography (TMS-EEG) analysis.

FIGURE 2

The waveforms of the global mean field power (GMFP) before and after multidisciplinary intensive rehabilitation treatment (MIRT). (A) The solid and dashed red curves depict GMFP in the responding group before and after MIRT. The gray shaded area shows a significant difference in GMFP amplitude before and after MIRT in the responding group. *p < 0.05 with correction. (B) The solid and dashed blue curves depict GMFP in the non-responding group before and after MIRT.

FIGURE 3

The evoked oscillatory power in the whole brain. The time-frequency plot shows the average energy for all electrodes in the whole brain before and after multidisciplinary intensive rehabilitation treatment (MIRT) in responding (A) and non-responding groups (B).

FIGURE 4

The evoked oscillatory power in the electrode of interest (EOI). (A) The topographic map shows a significant difference in the p-value in the target frequency band before and after MIRT. White dashed circles denote electrodes with significant differences (p-values corrected); Theta EOIs: Cp2 and Cp4; Beta EOI: Cz; Gamma (responding group) EOI: Cz; Gamma (non-responding group) EOI: PO3. (B) The time-frequency plot and histogram show the target frequency band power recorded from EOI before and after MIRT. *p < 0.05, ^***p < 0.001 with correction.

FIGURE 5

Association between changes in oscillatory power and clinical scales. (A) The p-values for the correlations between the change rate of the oscillatory power (theta, beta, and gamma) with significant changes and three kinds of clinical scales (UPDRS III, MMSE, and PDQ-39). (B) Scatter plots show significant correlations between the rate of change of beta power in the Cz electrode and the rate of change of gamma power in the PO3 electrode with MMSE. **p < 0.01 with correction.