Deep brain stimulation (DBS) of the subthalamic nucleus (STN) dramatically improves motor function and quality of life in PD yet may alter cognitive skills and mood (Progress Report). Our studies and others suggest that functional organization of basal ganglia-thalamocortical (BGTC) circuits and their course through STN underlies these effects. We hypothesize based on preliminary data that DBS focused in ventral STN (V-STN) selectively alters cognition and mood whereas motor benefit is widely distributed. We propose that this functional organization of STN will produce downstream effects in relevant pathways. In people with PD, we will compare the effects of unilateral monopolar DBS through selected V-STN and dorsal STN (D-STN) contacts on quantified motor, cognitive, and mood function with DBS-induced rCBF responses and presurgical MRI-based resting state functional connectivity (rs-fcMRI) networks. We found that rs-fcMRI identified key cortical and BGTC networks that are disrupted in PD and can provide an anchor for interpretation of downstream effects seen with rCBF responses. These studies have great potential to extend our understanding of the functional anatomy of the STN by delineating its role in motor, cognitive and mood behaviors in PD. These studies could reveal valuable insights into the clinical action of DBS and the pathophysiology of cognitive, mood and motor symptoms of PD. However, the importance of these studies goes beyond the specifics of DBS treatment for PD. We can take this unique opportunity to investigate the function of selected brain pathways in the region of the STN and how they affect cognitive, mood and motor function. Such basic observations have importance for understanding STN function and how impairments lead to disabilities in other basal ganglia disorders. These studies also have the potential to help refine DBS targeting, inform future development of new electrode design to shape current spread and improve programming strategies for optimal clinical benefit from STN DBS.

Public Health Relevance

Parkinson disease (PD) affects nearly one million people in North American and leads to substantial disability for many. Deep brain stimulation (DBS) has been a dramatic advance, yet there are still many unknowns about how this new therapy works. This proposal has the potential to reveal valuable insights into the clinical action of DBS and the pathophysiology of non-motor as well as motor manifestations of PD. However, the importance of these studies goes well beyond the specifics of DBS treatment for PD. We also can take advantage of this unique opportunity to investigate the function of selected brain pathways and how they affect cognitive, mood and motor function. Such basic observations have importance for understanding normal function as well as how impairments lead to disabilities in other basal ganglia related disorders with motor or cognitive dysfunction.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS041509-12
Application #
8522315
Study Section
Special Emphasis Panel (ZRG1-BDCN-C (02))
Program Officer
Sieber, Beth-Anne
Project Start
2001-04-01
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
12
Fiscal Year
2013
Total Cost
$488,099
Indirect Cost
$166,981
Name
Washington University
Department
Neurology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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