Deep brain stimulation (DBS) is an effective neurosurgical approach for a variety of neurological and psychiatric disorders including Parkinson's disease, essential tremor, epilepsy, and depression, among others. This research proposal is intended to advance DBS technology by developing a novel intraoperative monitoring approach based on electrochemical monitoring at the brain-electrode interface by use of carbon nanofiber (CNF) based electrode design. This approach utilizes technology developed at the Mayo Clinic, the Wireless Instantaneous Neurotransmitter Concentration Sensor (WINCS), an instrumentation system that combines digital telemetry with fast-scan cyclic voltammetry (FSCV) and amperometry, coupled to CNF based electrode technology developed at National Aeronautic and Space Administration (NASA) called WINCSnanotrode. Under Mayo IRB approved protocol, WINCS safety and feasibility has already been tested successfully in human patients undergoing DBS neurosurgery. Recently, CNF nanoelectrodes have been shown to be an excellent substrate for electrochemical detection demonstrating ultra high sensitivity, high signal to noise ratio, and rapid sampling, while at the same time providing an improved brain-electrode interface for more efficient stimulation, thereby conserving battery life. By virtue of its sub-second, chemically resolved recording, FSCV is recognized as state-of-the-art for measuring neurotransmitters, including dopamine, serotonin, norepinephrine, and adenosine, in laboratory animals. By correlating the release of neurotransmitter and therapeutic stimulation in real time, Mayo Clinic's WINCS coupled to NASA's WINCSnanotrode will provide a powerful new tool to assess the mechanism of DBS, guiding electrode placement, and testing accuracy and efficiency of stimulation. The three Specific Aims are (1) complete WINCS and WINCSnanotrode development to generate a device that is capable of use in humans for electrochemical sensing, (2) establish WINCSnanotrode approach for intraoperative neurochemical monitoring in a large-animal (pig) model of DBS neurosurgery, and (3) establish WINCS and WINCSnanotrode approach for intraoperative neurochemical monitoring in humans during DBS neurosurgery. We believe that WINCS and WINCSnanotrode technology engenders great potential to identify specific targets for DBS, to streamline the already long and difficult implantation procedure, to assess efficiency of stimulation parameter, and to improve the accuracy and efficiency of stimulating electrode.

Public Health Relevance

Deep brain stimulation (DBS) is an effective neurosurgical treatment for Parkinson's disease and other debilitating neuropathologies. The goal of this proposal is to develop a robust carbon nanofiber based electrochemical electrode capable of use in human DBS patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS075013-02
Application #
8312481
Study Section
Neurotechnology Study Section (NT)
Program Officer
Ludwig, Kip A
Project Start
2011-08-15
Project End
2016-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
2
Fiscal Year
2012
Total Cost
$309,628
Indirect Cost
$90,878
Name
Mayo Clinic, Rochester
Department
Type
DUNS #
006471700
City
Rochester
State
MN
Country
United States
Zip Code
55905
Trevathan, James K; Yousefi, Ali; Park, Hyung Ook et al. (2017) Computational Modeling of Neurotransmitter Release Evoked by Electrical Stimulation: Nonlinear Approaches to Predicting Stimulation-Evoked Dopamine Release. ACS Chem Neurosci 8:394-410
Marsh, Michael P; Kruchowski, James N; Hara, Seth A et al. (2017) Instrumentation for electrochemical performance characterization of neural electrodes. Rev Sci Instrum 88:085101
Lee, Kendall H; Lujan, J Luis; Trevathan, James K et al. (2017) WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions. Sci Rep 7:46675
Bennet, Kevin E; Tomshine, Jonathan R; Min, Hoon-Ki et al. (2016) A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain. Front Hum Neurosci 10:102
Grahn, Peter J; Lee, Kendall H; Kasasbeh, Aimen et al. (2015) Wireless control of intraspinal microstimulation in a rodent model of paralysis. J Neurosurg 123:232-242
Kim, Do Hyoung; Oh, Yoonbae; Shin, Hojin et al. (2014) Investigation of the reduction process of dopamine using paired pulse voltammetry. J Electroanal Chem (Lausanne) 717-718:157-164
Gupta, Rakesh K; Periyakaruppan, Adaikkappan; Meyyappan, M et al. (2014) Label-free detection of C-reactive protein using a carbon nanofiber based biosensor. Biosens Bioelectron 59:112-9
Manciu, Felicia S; Manciu, Marian; Durrer, William G et al. (2014) A Drude model analysis of conductivity and free carriers in boron-doped diamond films and investigations of their internal stress and strain. J Mater Sci 49:5782-5789
Gupta, Rakesh K; Meyyappan, M; Koehne, Jessica E (2014) Vertically aligned carbon nanofiber nanoelectrode arrays: electrochemical etching and electrode reusability. RSC Adv 4:22642-22650
Van Gompel, Jamie J; Bower, Mark R; Worrell, Gregory A et al. (2014) Increased cortical extracellular adenosine correlates with seizure termination. Epilepsia 55:233-44

Showing the most recent 10 out of 24 publications