Cortical and Cortico-Muscular Beta-Gamma Phase Amplitude Coupling during Different Locomotion Status and the Effects of Levodopa in Parkinson Disease

ObjectivesParkinsons disease (PD) is a neurodegenerative disorder that can cause motor impairments and gait problems. Non-invasive electrophysiological biomarkers like phase amplitude coupling (PAC) hold promise for understanding and managing PD. This study aims to investigate the modulations of levodopa and locomotion in cortical and cortico-muscular beta-gamma PAC by monitoring central EEG (cEEG) and gastrocnemius EMG (gEMG) and discuss their potential utility as biomarkers for monitoring motor impairments. MethodsThe cEEGs and gEMGs were recorded in 30 PD patients during sitting, standing, and free walking under OFF and ON dopaminergic medication. Spectral features, cEEG and cEEG-gEMG PAC were analyzed to assess the effects of levodopa, locomotion, and their correlations with PD symptoms. ResultsLonger gait cycle intervals and shorter step lengths were observed OFF levodopa, correlating with UPDRS-III. The cEEG beta-gamma PAC during sitting and standing, and cEEG-gEMG beta-gamma PAC during walking, positively correlated with UPDRS-III OFF levodopa. The cEEG alpha/low beta-gamma and cEEG-gEMG low beta-gamma PAC increased during levodopa withdrawal while walking, with the latter correlating with reduced step length. Step event-related PAC analysis unveiled the enhancement of alpha/beta cEEG-gamma gEMG PAC around heel strikes in ON levodopa compared to OFF. ConclusionsElevated cEEG and cEEG-gEMG beta-gamma PAC in various locomotion are associated with Parkinsonian motor impairments, whereas cEEG-gEMG low beta-gamma PAC is linked specifically to gait dysfunction. Levodopa administration enhances the dynamic fluctuations of alpha/beta oscillations during free walking. These findings demonstrated that the cortical and cortico-muscular couplings are significantly impacted by both levodopa and locomotion status, hinting the context-dependent nature of PAC and its potential utility in the development of gait phase-locked aDBS strategies for PD patients.