Functional MRI of Motor Planning and Execution in Parkinson's Disease and the Effect of Medication

Parkinson's disease (PD) is a neurodegenerative disorder resulting from the depletion of dopaminergic connections within the basal ganglia. PD patients commonly experience motor impairment (e.g., bradykinesia, tremor, etc.), as well as difficulty performing voluntary movements; however, these deficits may be due to deficits in motor planning and/or motor execution, both of which have been observed in PD. Previous studies have not adequately tested how selective deficits in each aspect of voluntary movement interact to affect motor function. In addition, although treatment with dopaminergic medications (e.g., levodopa and dopamine agonists) helps alleviate motor symptoms, the impact of levodopa on the brain's functional networks that govern movement has not yet been elucidated and requires further investigation. Hence, this thesis aims to use functional magnetic resonance imaging (fMRI) to investigate these issues. The thesis begins by investigating how PD alters brain activity during implicit motor planning using a task that assesses motor planning deficits without the need to execute movement. Second, the thesis investigates how PD alters brain activity during the performance of externally- and internally-timed movements, which show selective deficits in PD. Third, the thesis investigates whether PD patients experience difficulty performing internally-timed movements because of an internal timing deficit or a deficit in generating movement from rest. The latter two experiments had two manipulations: half of the participants performed the tasks without an explicit planning component, while the other half of participants received an informative prompt, permitting the assessment of motor execution deficits independently, as well as the interaction between motor planning and motor execution. In general, the results suggest that, relative to controls, PD patients exhibit alterations in brain activity during both motor planning and motor execution, and that patients utilize advanced information to influence motor behaviour in different ways. Medication appears to partially normalize brain activity, however the effects of medication are task dependent. The results of this thesis will foster future fMRI and PD research directions, potentially leading to the establishment of fMRI as an imaging modality to help understand how brain function changes in PD, as well as to evaluate the efficacy of future treatment options.