Imaging Core Aim 2, and Udall Project 2 Aim 2

More than one million people in the United States have Parkinson's disease (PD) and the prevalence is expected to double by 2040. Over 60% of these individuals will develop debilitating postural instability and gait disturbances (PIGD), including freezing of gait (FOG). With disease progression, axial motor symptoms typically become resistant to dopamine replacement therapies (e.g. levodopa) and a primary source of disability and morbidity. While subthalamic (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) using standard locations and stimulation parameters can be highly effective for the treatment of the cardinalmotorsymptomsof PD, both treatments often fail to control levodopa-resistant motor features of PD such as PIGD. DBS can also impair cognitive function which further exacerbates PIGD, particularly when the task requires attentional resources. Thus, despite considerable improvements in appendicular bradykinesia, rigidity and tremor with conventional DBS, the disease can continue to be dominated by PIGD, leading to increased falls, decreased mobility, and increased rate of hospitalization and morbidity. This is why one of the top NINDS priorities for clinical research in PD is the development of novel therapeutic approaches, such as DBS targeting, to treat levodopa-resistant motor symptoms.

This study will provide crucial information to elucidate the functional properties of the networks involved in Deep Brain Stimulation (DBS) treatment. By refining our understanding of the neural networks involved in stimulation of DBS targets, we will improve our ability to program patients to enhance their clinical outcomes and minimize side effects.