How the Loss of Dopamine and Dopamine-Restoring Medicines Affect Movement Performance

Objective: In the central nervous system, short-term plasticity can be defined as a change in connection strength that is induced by receiving presynaptic inputs. Dopamine (DA), a neuromodulatory neurotransmitter, is believed to play a role in short-term plasticity. \[18F\]dopa positron emission tomography (PET) studies have shown progressive impairment of presynaptic dopaminergic (DAergic) function in both healthy elderly subjects (HES) and patients with Parkinson's disease (PD). Both PD and HES are characterized by a progressive decline in performance on some motor tasks and changes in activity in brain areas involved in motor control (including motor control by cognitive functions) as shown by functional imaging studies. However, little is known about the exact neurobiological mechanisms linking DAergic function, brain activity and motor (and cognitive) performances in PD and HES. In the present study, we hypothesize that impaired performance on some motor tasks in those subject groups is related to a dysfunction of task-specific functional connections between areas participating in motor control. In addition, the brain activation with fMRI across sessions and across subjects in the healthy group will be examined to investigate the reliability of the fMRI techniques. Study population: We will study two groups of participants: one group of patients with mild-to-moderate PD and one group of healthy subjects. Design: We will measure cerebral activity in baseline condition and during the execution of sequential finger movements using perfusion functional magnetic resonance imaging (fMRI) in the three subject groups. The reliability of fMRI data across sessions and across subjects in the healthy young group and brain activity in patients with PD will be studied "off" and then "on" medication. Outcome measures: Imaging data will be compared in terms of both regional activity and effective connectivity using the statistical parametric mapping (SPM) software. These experiments should lead to better understanding the pathophysiology of the mesencephalic DAergic system in human motor control and may lead to better treatment strategies in PD.