We investigated the effect of acute levodopa administration on movement-related cortical oscillations and movement velocity in Parkinson's disease (PD). Patients with PD on and off medication and age- and sex-matched healthy controls performed a ballistic upper limb flexion movement as fast and accurately as possible while cortical oscillations were recorded with high-density electroencephalography. Patients off medication were also studied using task-based functional magnetic resonance imaging (fMRI) using a force control paradigm. Percent signal change of functional activity during the force control task was calculated for the putamen and subthalamic nucleus (STN) contralateral to the hand tested. We found that patients with PD off medication had an exaggerated movement-related beta-band (13-30 Hz) desynchronization in the supplementary motor area (SMA) compared to controls. In PD, spectral power in the beta-band was correlated with movement velocity. Following an acute dose of levodopa, we observed that the beta-band desynchronization in the SMA was reduced in PD, and was associated with increased movement velocity and increased voltage of agonist muscle activity. Further, using fMRI we found that the functional activity in the putamen and STN in the off medication state, was related to how responsive that cortical oscillations in the SMA of PD were to levodopa. Collectively, these findings provide the first direct evaluation of how movement-related cortical oscillations relate to movement velocity during the ballistic phase of movement in PD and demonstrate that functional brain activity in the basal ganglia pathways relate to the effects of dopaminergic medication on cortical neuronal oscillations during movement.
Keywords: BOLD, blood oxygen level dependent; Ballistic movements; DBS, deep brain stimulation; ECoG, electrocorticography; EEG; EEG, electroencephalography; EMG, electromyography; ERSP, event-related power spectral perturbation; FDR, false discovery rate; HC, healthy control; ICA, independent component analysis; LFP, local field potential; Levodopa; M1, primary motor cortex; MDS-UPDRS, Movement Disorder Society Unified Parkinson's Disease Rating Scale; MEG, magnetoencephalography; MPA, measure projection analysis; MVC, maximum voluntary contraction; MoCA, Montreal Cognitive Assessment; PD, Parkinson's disease; PD-OFF, off medication (levodopa) day; PD-ON, on medication (levodopa) day; PET, positron emission tomography; Parkinson's disease; ROI, regions of interest; S1, primary somatosensory cortex; SMA, supplementary motor area; SNc, substantia nigra pars compacta; STN, subthalamic nucleus; Supplementary motor area; fMRI; fMRI, functional magnetic resonance imaging; iEMG, integrated electromyography; rCBF, regional cerebral blood flow.