Levodopa and Subthalamic Nucleus Deep Brain Stimulation Modulate Excitation/Inhibition Balance and the Neural Encoding of Isochronous Sequences in Persons With Parkinson's Disease

Temporally regular auditory stimuli, as found in isochronous sound streams, metronome beats, or music, are often used in rhythmic auditory stimulation (RAS) interventions to initiate and stabilize the temporal coordination of motor plans in persons with Parkinson's disease (pwPD). Research suggests that RAS promotes the recruitment of a cerebellar-prefrontal network and recalibrates abnormal β-band synchronization in the striato-thalamo-cortical pathway. These cuing effects can resemble those observed via dopaminergic treatments (e.g., levodopa) and deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). Here, we investigated the influence of both levodopa administration and STN DBS on the neural encoding of isochronous auditory sequences in pwPD. A comprehensive analysis of electroencephalography (EEG) data revealed changes in β-band event-locked neural responses, as well as event-related potentials, neural tracking of rhythm (δ-band inter-trial phase coherence), and excitation/inhibition balance (E/I) as a function of these treatments. Furthermore, we characterized the link between changes in E/I and motor symptom severity (UPDRS-III) with levodopa administration. We suggest that characterizing individual responses to specific treatments is a fundamental step in tailoring rehabilitation protocols and optimizing intervention efficacy.