Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus inturnus (GPi) represent established therapies for medically refractory Parkinson's disease (PD). However, selection of therapeutic stimulation parameters is primarily based on clinical intuition, and the DBS electrode design is not optimized to either nucleus. The fundamental goal of this Bioengineering Research Grant (PA-06-419) is to quantify the volume of tissue activated (VTA) by DBS in PD patients. We recently developed the computational infrastructure necessary to accurately predict the DBS VTA on a patient-specific basis (R21 NS-50449 PI: Mclntyre). In the first aim of the study we will create a patient-specific model of DBS for each subject enrolled in an NIH sponsored clinical trial comparing the therapeutic efficacy of STN DBS to GPi DBS (R01 NS-37959 PI: Vitek). Our central hypothesis is that there exists a target volume of tissue that should be stimulated for maximal therapeutic benefit from DBS, and the size and shape of the target VTA is specific to each nucleus. Characterization of the different anatomical structures activated by DBS across a large patient population (60 STN and 60 GPi) will allow us to define probabilistic maps of therapeutic and non-therapeutic regions for stimulation. These results will allow definition of the therapeutic target VTA for each nucleus. In the second aim of this study we will use our quantitative knowledge of the target VTA for STN DBS and the target VTA for GPi DBS to develop computer algorithms that optimize the clinical selection of therapeutic stimulation parameter settings. We will then prospectively test our patient-specific theoretically optimal stimulation parameter settings on a cohort of 20 new patients. Finally, the third aim of this study will be to design DBS electrodes that are customized to the STN and GPi. We will reverse engineer the design of the DBS electrode such that they generate a VTA shape that better matches the anatomical and electrical constraints of either the target VTA for STN or target VTA for GPi. The scientific knowledge gained from this project will advance the clinical utility of DBS for PD. In addition, the methodology and technology developed in this study will be directly applicable to the study of DBS in other disorders such as essential tremor, dystonia, epilepsy, obsessive-compulsive disorder, depression, and Tourette's syndrome.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS059736-04
Application #
7878525
Study Section
Special Emphasis Panel (ZRG1-BDCN-K (10))
Program Officer
Ludwig, Kip A
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
4
Fiscal Year
2010
Total Cost
$334,590
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Choi, Ki Sueng; Riva-Posse, Patricio; Gross, Robert E et al. (2015) Mapping the ""Depression Switch"" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation. JAMA Neurol 72:1252-60
McIntyre, Cameron C; Chaturvedi, Ashutosh; Shamir, Reuben R et al. (2015) Engineering the next generation of clinical deep brain stimulation technology. Brain Stimul 8:21-6
Riva-Posse, Patricio; Choi, Ki Sueng; Holtzheimer, Paul E et al. (2014) Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression. Biol Psychiatry 76:963-9
Lujan, J Luis; Chaturvedi, Ashutosh; Choi, Ki Sueng et al. (2013) Tractography-activation models applied to subcallosal cingulate deep brain stimulation. Brain Stimul 6:737-9
McIntyre, Cameron C; Foutz, Thomas J (2013) Computational modeling of deep brain stimulation. Handb Clin Neurol 116:55-61
Dietz, Jenna; Noecker, Angela M; McIntyre, Cameron C et al. (2013) Stimulation region within the globus pallidus does not affect verbal fluency performance. Brain Stimul 6:248-53
Chaturvedi, Ashutosh; Lujan, J Luis; McIntyre, Cameron C (2013) Artificial neural network based characterization of the volume of tissue activated during deep brain stimulation. J Neural Eng 10:056023
Gorniak, Stacey L; McIntyre, Cameron C; Alberts, Jay L (2013) Bimanual force coordination in Parkinson's disease patients with bilateral subthalamic deep brain stimulation. PLoS One 8:e78934
Chaturvedi, Ashutosh; Foutz, Thomas J; McIntyre, Cameron C (2012) Current steering to activate targeted neural pathways during deep brain stimulation of the subthalamic region. Brain Stimul 5:369-377
Lujan, J Luis; Chaturvedi, Ashutosh; Malone, Donald A et al. (2012) Axonal pathways linked to therapeutic and nontherapeutic outcomes during psychiatric deep brain stimulation. Hum Brain Mapp 33:958-68

Showing the most recent 10 out of 22 publications