Abstract
Objective: Randomized clinical trials have shown that aerobic exercise attenuates motor symptom progression in Parkinson's disease, but the underlying neural mechanisms are unclear. Here, we investigated how aerobic exercise influences disease-related functional and structural changes in the cortico-striatal sensorimotor network, which is involved in the emergence of motor deficits in Parkinson's disease. Additionally, we explored effects of aerobic exercise on tissue integrity of the substantia nigra, and on behavioral and cerebral indices of cognitive control. Methods: The Park-in-Shape trial is a single-center, double-blind randomized controlled trial in 130 Parkinson's disease patients who were randomly assigned (1:1 ratio) to aerobic exercise (stationary home-trainer) or stretching (active control) interventions (duration: six months). An unselected subset from this trial (exercise: n=25, stretching: n=31) underwent resting-state functional and structural magnetic resonance imaging, and an oculomotor cognitive control task (pro- and anti-saccades), at baseline and at six-month follow-up. Results: Aerobic exercise, but not stretching, led to increased functional connectivity of the anterior putamen with the sensorimotor cortex relative to the posterior putamen. Behaviorally, aerobic exercise also improved cognitive control. Furthermore, aerobic exercise increased functional connectivity in the right frontoparietal network, proportionally to fitness improvements, and it reduced global brain atrophy. Interpretation: MRI, clinical, and behavioral results converge towards the conclusion that aerobic exercise stabilizes disease progression in the cortico-striatal sensorimotor network and enhances cognitive performance.
