Essential tremor (ET) is the most common movement disorder in the United States, affecting 4% of all adults over the age of 40. For individuals whose motor symptoms are refractory to medication and significantly impair their daily living, deep brain stimulation (DBS) is considered to be the only therapeutic option. Despite recent advances in DBS technology, a significant portion of ET patients with DBS implants will receive inadequate tremor control because of poorly placed DBS leads, while others will lose efficacy of the therapy after 1-2 years due in part to inflexible neurostimulator programming options. There is a strong and growing clinical need for implantable DBS lead designs that can enable clinicians to better sculpt electric fields within the brain, especially in cases where stimulation through a poorly placed DBS lead results in low-threshold side-effects. Our recent studies with a radially-segmented DBS lead have shown promising results, but knowing how to program the stimulation settings on such a lead remains a critical challenge towards making these leads practical in a clinical setting. Our proposed study will integrate high-field magnetic resonance imaging, computational modeling, and electrophysiology to develop an experimentally-validated computational programming algorithm that facilitates clinical determination of subject-specific neurostimulator settings through high-dimensional DBS electrode arrays. Specifically, we will: 1) develop a computational algorithm that can simplify the programming process of thalamic deep brain stimulation leads with radially-segmented electrode arrays;2) quantify the degree to which the computational algorithms can accurately predict current steering through poorly targeted DBS arrays in the thalamus in non-human primates;and 3) compare the layer-specific neuronal dynamics induced in primary motor cortex (M1) during stimulation of the cerebellothalamic versus thalamocortical pathway in non-human primates.

Public Health Relevance

Deep brain stimulation (DBS) is a proven therapy for patients with medication-refractory essential tremor, but a significant portion of patients with these implants do not receive adequate tremor control because of poorly placed DBS leads or inflexible DBS programming options. There is a strong and growing clinical need for implantable DBS lead designs that can enable clinicians to better sculpt electric fields in the brain. Our research study will experimentally evaluate a computational modeling approach to program a novel DBS lead with radially-segmented electrodes for improved targeting of stimulation within thalamus so as to improve the functional outcome for all patients requiring DBS to manage their essential tremor.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS081118-01
Application #
8419742
Study Section
Special Emphasis Panel (NOIT)
Program Officer
Ludwig, Kip A
Project Start
2012-09-30
Project End
2016-07-31
Budget Start
2012-09-30
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$366,689
Indirect Cost
$106,668
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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Slopsema, Julia P; Peña, Edgar; Patriat, Remi et al. (2018) Clinical deep brain stimulation strategies for orientation-selective pathway activation. J Neural Eng 15:056029
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Peña, Edgar; Zhang, Simeng; Deyo, Steve et al. (2017) Particle swarm optimization for programming deep brain stimulation arrays. J Neural Eng 14:016014
Lehto, Lauri J; Slopsema, Julia P; Johnson, Matthew D et al. (2017) Orientation selective deep brain stimulation. J Neural Eng 14:016016
Teplitzky, Benjamin A; Zitella, Laura M; Xiao, YiZi et al. (2016) Model-Based Comparison of Deep Brain Stimulation Array Functionality with Varying Number of Radial Electrodes and Machine Learning Feature Sets. Front Comput Neurosci 10:58
Xiao, YiZi; Zitella, Laura M; Duchin, Yuval et al. (2016) Multimodal 7T Imaging of Thalamic Nuclei for Preclinical Deep Brain Stimulation Applications. Front Neurosci 10:264
Xiao, YiZi; Peña, Edgar; Johnson, Matthew D (2016) Theoretical Optimization of Stimulation Strategies for a Directionally Segmented Deep Brain Stimulation Electrode Array. IEEE Trans Biomed Eng 63:359-71
Connolly, Allison T; Vetter, Rio J; Hetke, Jamille F et al. (2016) A Novel Lead Design for Modulation and Sensing of Deep Brain Structures. IEEE Trans Biomed Eng 63:148-57

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