Searching for a neurophysiological marker of ON/OFF state in PD

Motor fluctuations (MF) in Parkinson’s disease (PD) are episodic changes in motor performance due to variable responses to levodopa therapy, marked by "on" and "off" periods. Current assessments rely on subjective patient reports and clinical observation, which may miss subtle changes. Neurophysiological markers obtained from transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) hold promise as objective indicators of cortical excitability related to motor function.

Eighteen patients (mean age 59.4±19.1 years; 72.2% males; disease duration 10.8±8.8 years; LEDD 906.8±349.1 mg) participated. A repeated measures t-test showed that the TMS-EEG GMFP of the right primary motor cortex (M1R) significantly distinguished "on" vs. "off" states (p<0.000536). Regression analysis, controlled for LEDD, revealed that ?GMFP N100 of primary visual cortex (V1R) variability explained about 49.9% of the variance in motor improvement (ΔMDS-UPDRS-III, F(2,13)=6.46, p=0.011, adjusted R²=0.42). Larger N100 amplitude increases in V1R (visual cortex) strongly predicted greater motor improvement (β=–0.79, p=0.003). LEDD showed a non-significant trend.

TMS-EEG measures from motor and occipital regions may serve as objective biomarkers of dopaminergic response in fluctuating PD. The motor cortex distinctly differentiates "on" and "off" states, while the visual cortex might provide real-time, continuous feedback on levodopa effects. These neurophysiological markers could reduce reliance on subjective assessments and improve monitoring and personalized treatment.