Deep brain stimulation (DBS) is a surgical procedure that is effective in improving the cardinal motor signs of advanced Parkinson's disease (PD). Bilateral STN DBS has been shown to produce cognitive deficits which are a contraindication for performing this procedure on some PD patients. Because most daily activities consist of cognitive and motor components that are performed concurrently, it would be predicted that even in those patients in whom the procedure is performed successfully, it is likely that cognitive declines will compromise their improved motor function. The potential effects of these declines on motor function have not been studied as current clinical assessments do not examine cognitive and motor function simultaneously and may therefore underestimate the deficits in cognitive and motor function. We have shown that cognitive and cognitive-motor function is compromised to a greater extent during bilateral, compared to unilateral STN DBS. Preliminary data indicate a neurocomputational approach to the selection of DBS parameters that minimizes current spread into non-motor regions of the STN mitigates cognitive declines while motor benefits are maintained. Based on these findings, we hypothesize that the spread of current to non-motor regions of the STN disrupts the processing of cognitive information within the basal ganglia and produces the cognitive declines observed during STN DBS which leads to diminished motor performance. We further hypothesize that maximizing current spread in the sensorimotor region of the STN while minimizing spread to non-motor regions of the STN will mitigate cognitive declines without compromising gains in motor function. Clinical cognitive and motor testing and a cognitive-motor dual-task paradigm (i.e. working memory task paired with a upper extremity force-tracking task) will be used to simultaneously quantify cognitive and motor performance. Data will be collected from 48 advanced PD patients undergoing bilateral STN DBS across three conditions: 1) pre-DBS, 2) post-DBS with clinically defined DBS parameters and 3) post-DBS with model derived parameters in which the volume of tissue activated (VTA) within the non-motor region of the STN is minimized. The results from this project will likely improve the cognitive-motor outcomes associated with DBS and enhance the quality of life for those patients. In addition, the technology and methodology developed in this project could help standardize the process of clinical programming, especially at centers lacking extensive experience and expertise in the nuances of DBS programming.

Public Health Relevance

The goals of this project are to assess cognitive and motor performance in Parkinson's disease (PD) patients under unilateral compared to bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) during single- and dual-task conditions and to predict the relationship between the volume of tissue activated in the motor and non-motor regions of the STN and changes in cognitive and motor function under dual-task conditions. These results will then be used to select programming parameters that will minimize spread of current into non-motor regions of the STN to reduce the level of cognitive impairment while maintaining improvements in motor function. The combined use of this dual-task paradigm and visualization software has the potential to allow clinicians to better achieve the fundamental goal of DBS: provide maximal motor response while minimizing cognitive-motor losses.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Sieber, Beth-Anne
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Cleveland Clinic Lerner
Other Basic Sciences
Schools of Medicine
United States
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