Dynamic cortical inhibition imbalance as a biomarker of clinical progression in early Parkinson's disease.

Objective: The role of bilateral cortical inhibition in motor compensation during the progression of early Parkinson's disease (PD) remains unclear. This study aims to investigate the dynamic balance of between-hemispheric inhibition and the clinical relevance of its neurophysiological indicators.

Methods: Paired-pulse TMS was used to investigate the activity of different intracortical inhibitory circuits in 90 PD patients and 43 healthy controls during the "on medication" state. Spearman's rank correlations and general linear model (GLM) were used to analyze the association between TMS measures and disease severity, while receiver operating characteristic (ROC) analysis was used to identify the best indicator to predict disease progression at 12 months.

Results: As PD advances, both cross-sectional and longitudinal study confirm the difference in short-interval intracortical inhibition (SICI) increase while long-interval intracortical inhibition (LICI) tends to decrease, leading to a rising difference in the ratio of SICI differences and LICI differences between the two hemispheres (SICI'/LICI'). The SICI'/LICI' reflecting the variation represents motor reserve capacity between hemisphere in some extent. Furthermore, GLM revealed that the change of SICI'/LICI' ratio was longitudinally correlated with the deterioration of motor and non-motor symptoms over time. Finally, ROC analysis validated the change of SICI'/LICI' as a potential predictor of PD progression.

Conclusions: The present study has shown that the dysfunction of inhibitory pathway was correlated with disease severity and progression. Also, the change of SICI'/LICI' ratio was a valuable tool for assessing the dynamic changes in cortical compensation mechanisms as well as PD progression.