Multimodal imaging investigation of therapeutic mechanisms of exercise in Parkinson’s disease : effects on dopamine release, ventral striatal activity and neuroinflammation

Objective: Exercise has been shown to be beneficial for people with Parkinson’s disease (PD) however, the underlying mechanisms are unknown. Evidence from animal models has shown exercise-induced changes in the dopaminergic system and decreased neuroinflammation, but these changes have yet to be studied in patient populations. The purpose of this thesis was to study the effects of exercise on dopaminergic function and neuroinflammation using multimodal neuroimaging in subjects with PD. Methods: Two different comparisons were conducted using positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). First, a cross-sectional study compared dopamine release, and ventral striatal activity, between PD habitual exercisers and sedentary PD subjects. Next, a prospective trial was conducted to compare the effects of exercise on ventral striatal activity, dopamine release and neuroinflammation. Results: The cross-sectional study showed that habitual exercisers have greater dopamine release in the caudate nucleus in response to exercise and greater activation of the ventral striatum in response to monetary reward, compared to sedentary PD subjects. Similarly, the prospective trial showed increased dopamine release in the caudate nucleus in response to repetitive transcranial stimulation after 3 months of aerobic exercise compared to a stretching control group. Moreover, the aerobic group showed increased activity of the ventral striatum in response to monetary reward, compared to the control group. The aerobic group also showed decreased neuroinflammation in the thalamus, globus pallidus and cerebellum, but those findings were highly dependent on the type of analysis method used and technical limitations of the PET tracer. Conclusion: The benefits of exercise in PD are likely driven by changes to the dopaminergic system. Aerobic exercise increased dopamine release in the caudate nucleus and increased responsivity in the ventral striatum, suggesting changes to the dorsal striatum and mesolimbic dopaminergic system. The exercise-induced changes in neuroinflammation are limited to the analysis methods and technical constraints of imaging neuroinflammation. Collectively, the findings of this thesis support the use of exercise as an adjunct therapy for PD by showing that the benefits of exercise in PD are the result of neurological changes to the dopaminergic system.Medicine, Faculty ofGraduat