PROJECT SUMMARY/ABSTRACT Parkinson’s disease (PD) is the fastest growing neurological disease, outpacing even Alzheimer’s disease. Aerobic exercise is universally accepted as an integral part of PD treatment, and stationary cycling in particular has been suggested to be an ideal exercise modality for people with PD. Our seminal tandem cycling study was the first to utilize forced exercise (FE) in human PD patients and demonstrate a 30% improvement in clinical ratings compared to voluntary exercise (VE) at a self-selected rate. FE is a mode of high intensity aerobic exercise originating in animal models of PD in which the voluntary pedaling rate (cadence) of exercise is augmented, but not replaced. Aerobic exercise, including FE, has demonstrated potential as a disease- modifying intervention; however, in order to truly examine disease-modification, the mechanism of action must be evaluated. Hypersynchrony of motor circuits within the basal ganglia is associated with cardinal motor signs such as bradykinesia, tremor, and rigidity in individuals with PD. Recent animal studies using FE evaluated local field potentials (LFP) from the primary motor cortex (M1) and reported an attenuation of neural hypersynchrony in the beta (13-35Hz) frequency band associated with improved motor function. Until now, neural activity from the basal ganglia has been isolated to animal models or highly invasive human studies where the deep brain stimulator (DBS) wires have been externalized. Recently, advances in DBS technology in humans allows, for the first time, direct neural activity recording from the subthalamic nucleus (STN) of the basal ganglia in individuals implanted with the Medtronic Percept DBS system. This project aims to record neural activity from the STN during two modes, FE and VE, in individuals with PD. Our underlying hypothesis is that high intensity exercise reduces STN hypersynchrony which facilitates cortico-basal ganglia thalamocortical circuit functionality thereby improving motor function following exercise. Fifteen PwPD who have previously undergone DBS surgery utilizing the Percept system will complete a single FE and VE exercise session on a stationary cycle while off antiparkinsonian medication. Bilateral neural activity of the STN will be continuously recorded for approximately 130 minutes total (pre-exercise, during FE or VE and post-exercise) on two separate days. The MDS-UPDRS III Motor Exam and an upper extremity grip force tracking paradigm will be used to determine motor response to exercise. While we expect improvements in performance and attenuation in beta band activity following a single bout of FE and VE, it is hypothesized that FE will experience superior results due to the higher cycling cadence resulting in greater beta attenuation.

PROJECT NARRATIVE The aim of this project is to determine the effects of two modes of high intensity exercise, forced exercise (FE) and voluntary exercise (VE), on the pattern of neural activity within the subthalamic nucleus of the basal ganglia in individuals with Parkinson’s disease (PD). Fifteen individuals with PD who have previously undergone deep brain stimulation (DBS) surgery utilizing the Medtronic Percept system will complete a single FE and VE exercise session on a stationary cycle while Off antiparkinsonian medication. Our underlying hypothesis is that high intensity exercise reduces STN hypersynchrony which facilitates cortico-basal ganglia thalamocortical circuit functionality thereby improving motor function, measured by clinical outcomes and an upper extremity force tracking paradigm.