The overall goal of this study is to characterize the changes in motor pathway activity produced by deep brain stimulation in the subthalamic nucleus (STN DBS) in patients with Parkinson's disease (PD) using functional magnetic resonance imaging (fMRI). PD is one of the most common neurodegenerative disorders, affecting over 1 million people in the United States. It causes significant human suffering and has annual cost of approximately $24 billion in health care resources and lost wages. STN DBS provides excellent symptom relief for PD patients in the late stages of the disease when medical therapies are no longer effective or produce too many unwanted side effects. Present understanding of the mechanisms of STN DBS for PD is derived primarily for animal models and inferences drawn from lesional therapies in humans. Our preliminary data suggest that fMRI produces activation in the ipsilateral globus pallidus and thalamus during therapeutically effective STN DBS for PD. The present study will use fMRI for the in vivo interrogation of the neuronal circuitry and mechanisms responsible for the therapeutic efficacy of DBS. Specifically, the aims of the study are 1) to determine the pattern of fMRI activation associated with optimal relief in Parkinsonian motor signs during STN DBS, 2) to determine the relationship between functional MRI activation and clinical efficacy in DBS of the STN in PD and 3) to determine the pattern of activation associated with unilateral stimulation which results in bilateral symptom relief. It is hypothesized that fMRI during DBS of the STN in PD will 1) produce a consist pattern of activation in the globus pallidus and thalamus with optimal symptom relief, 2) produce activation that will positively correlate in degree with the amount of Parkinsonian motor symptom relief, and 3) in subjects with strong bilateral symptom relief from unilateral stimulation will produce a bilateral pattern of activation in during unilateral stimulation. fMRI represents a unique opportunity for the in vivo to study and better understand the neuronal circuitry and mechanisms underlying the therapeutic effect of STN DBS in PD. It allows for the direct correlation of the motor pathway response to DDS with observed therapeutic benefit. We believe that information gained from present proposal will have a significant positive impact on future clinical applications of DBS therapy for Parkinson's Disease. ? ? ?