Neural Mechanisms underlying the benefits of Aerobic Exercise in Advanced Parkinson's disease - PROJECT SUMMARY/ABSTRACT A substantial body of evidence supports the concept that high intensity aerobic exercise improves Parkinson’s disease (PD) symptomology in mild to moderate people with PD (PwPD). Despite advances in appreciating the benefits of exercise as an adjunct to treating PD, there is an absence of data regarding how, or if, exercise is effective for advanced PwPD. Considering 25-50% of PwPD are classified as advanced, it is critical to systematically determine the optimal approach to exercise for this vulnerable group of PwPD. Recent advances in DBS technology, Medtronic Percept device, now allow for the stimulation of a target structure within the basal ganglia and recording from that same structure. The proposed project will leverage advances in DBS technology utilized by advanced PwPD to address two fundamental gaps related to aerobic exercise and advanced PD: 1) Do the advanced PwPD experience enhanced motor, cognitive and dual-task performance following aerobic exercise? and 2) What is the neural mechanism(s) underlying potential exercise induced improvements? For the first time, advanced PwPD with DBS will be enrolled in a long-term exercise intervention while gathering neural activity from the subthalamic nucleus (STN) via the Medtronic Percept DBS system and cerebral cortex via EEG to determine the neural underpinnings associated with potential improvements following long-term aerobic exercise. Fifty-one advanced PwPD with STN DBS will be equally randomized to: voluntary exercise (VE), forced exercise (FE) or usual and customary care (UCC) control group. The VE group will exercise at a cadence of 60rpms or less; the FE group will exercise on a motorized cycle that augments their self-selected pace to increase cadence to 80-90 rpms. The FE and VE groups will exercise 3x/wk for 8-weeks (24 sessions). The UCC group will maintain their current level of activity. Assessments of motor, cognitive, and dual-task function, along with cortical and subcortical neural data, will be gathered at baseline, end of treatment, and 4-weeks following treatment cessation. The hypothesis being tested is that sustained aerobic exercise normalizes activity within the cortico-basal ganglia-thalamic (CBT) network by reducing beta oscillations in the STN; reduced STN beta oscillations serve to restore neural activity within cortical regions which collectively underlie enhanced motor, cognitive and dual-task performance. By systematically evaluating the effects of two modes of aerobic exercise on motor, cognitive and dual-task performance relative to a no-exercise control group, the proposed project provides the much-needed clinical exercise guidance for a population largely ignored in the exercise and rehabilitation literature. Recording neural data from the STN and cortical areas before and after long-term exercise will provide unprecedented insight into neural mechanism(s) underlying the expected positive effects of exercise, which may ultimately guide DBS programming and future therapeutic interventions for PD.
