Subthalamic deep brain stimulation (DBS) is an effective for the treatment of Parkinson's disease (PD). However, little is known about the specific neural pathway(s) responsible for therapeutic benefit. Direct stimulation of either the hyperdirect pathway and/or the subthalamopallidal pathway represents two of the most likely candidates as the """"""""target"""""""". Therefore, the goal of this project is to combine patient-specific 7T imaging and neurostimulation models together to enable probabilistic identification of the stimulation pathways linked to changes in clinical outcome measures recorded from subthalamic DBS patients. This study will rely on tractography-activation models (TAMs) to guide clinical testing on a cohort of 30 subthalamic DBS patients. Our multi-disciplinary approach will integrate the latest advances in neuroimaging, neurostimulation modeling, and quantitative clinical outcome measures to customize DBS to these patients.
The first aim will acquire high- resolution 7T MRI data prior to their implant surgery. These images will provide unparalleled anatomical characterization of each patient.
The second aim will create patient-specific TAMs for each subject. These models will enable us to define theoretically optimal settings for focused activation of either the hyperdirect pathway or the subthalamopallidal pathway.
The third aim will quantify the clinical outcomes achieved with stimulation parameters defined by either the TAM or traditional clinical practice. These clinical results will be coupled with the TAM predictions to create a probabilistic tractography-activation atlas (PTAA) for the subthalamic region. The results of this study will help identify optimal implantation locations for DBS electrodes, and enable theoretical prediction of stimulation parameter settings that focus activation on the targeted pathways and/or avoid side-effect pathways.

Public Health Relevance

Deep brain stimulation (DBS) is a powerful clinical technology, positively impacting the lives of tens of thousands of patients. The goal of this project is to continue the evolution of DBS patient-specific computer models and use them to better understand the mechanisms of the therapy. Results from this project will enable more efficacious stimulation strategies for patients implanted with DBS systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS085188-02
Application #
8724575
Study Section
(NOIT)
Program Officer
Sieber, Beth-Anne
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Milham, Michael P; Ai, Lei; Koo, Bonhwang et al. (2018) An Open Resource for Non-human Primate Imaging. Neuron 100:61-74.e2
Patriat, Rémi; Cooper, Scott E; Duchin, Yuval et al. (2018) Individualized tractography-based parcellation of the globus pallidus pars interna using 7T MRI in movement disorder patients prior to DBS surgery. Neuroimage 178:198-209
Gunalan, Kabilar; Howell, Bryan; McIntyre, Cameron C (2018) Quantifying axonal responses in patient-specific models of subthalamic deep brain stimulation. Neuroimage 172:263-277
Peña, Edgar; Zhang, Simeng; Patriat, Remi et al. (2018) Multi-objective particle swarm optimization for postoperative deep brain stimulation targeting of subthalamic nucleus pathways. J Neural Eng 15:066020
Lempka, Scott F; Howell, Bryan; Gunalan, Kabilar et al. (2018) Characterization of the stimulus waveforms generated by implantable pulse generators for deep brain stimulation. Clin Neurophysiol 129:731-742
Plantinga, Birgit R; Temel, Yasin; Duchin, Yuval et al. (2018) Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI. Neuroimage 168:403-411
Anderson, Ross W; Farokhniaee, AmirAli; Gunalan, Kabilar et al. (2018) Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation. Brain Stimul 11:1140-1150
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
Amundsen Huffmaster, Sommer L; Van Acker 3rd, Gustaf M; Luchies, Carl W et al. (2018) Muscle Synergies Obtained from Comprehensive Mapping of the Cortical Forelimb Representation Using Stimulus Triggered Averaging of EMG Activity. J Neurosci 38:8759-8771
Duchin, Yuval; Shamir, Reuben R; Patriat, Remi et al. (2018) Patient-specific anatomical model for deep brain stimulation based on 7 Tesla MRI. PLoS One 13:e0201469

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