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)
Type
Research Project (R01)
Project #
5R01NS081118-03
Application #
8720828
Study Section
(NOIT)
Program Officer
Ludwig, Kip A
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Biomedical Engineering
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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
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
Xiao, YiZi; Pena, 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; Muralidharan, Abirami; Hendrix, Claudia et al. (2015) Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator. J Neural Eng 12:066012
Connolly, Allison T; Jensen, Alicia L; Baker, Kenneth B et al. (2015) Classification of pallidal oscillations with increasing parkinsonian severity. J Neurophysiol 114:209-18
Zitella, Laura M; Xiao, YiZi; Teplitzky, Benjamin A et al. (2015) In Vivo 7T MRI of the Non-Human Primate Brainstem. PLoS One 10:e0127049
Xiao, YiZi; Johnson, Matthew D (2015) Spherical statistics for characterizing the spatial distribution of deep brain stimulation effects on neuronal activity. J Neurosci Methods 255:52-65
Zitella, Laura M; Teplitzky, Benjamin A; Yager, Paul et al. (2015) Subject-specific computational modeling of DBS in the PPTg area. Front Comput Neurosci 9:93
Agnesi, Filippo; Muralidharan, Abirami; Baker, Kenneth B et al. (2015) Fidelity of frequency and phase entrainment of circuit-level spike activity during DBS. J Neurophysiol 114:825-34
Johnson, Matthew D; Lim, Hubert H; Netoff, Theoden I et al. (2013) Neuromodulation for brain disorders: challenges and opportunities. IEEE Trans Biomed Eng 60:610-24

Showing the most recent 10 out of 14 publications