@article{7c16e90490ed4cb7990d717c2e291acb,
title = "WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions",
abstract = "There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.",
author = "Lee, {Kendall H.} and Lujan, {J. Luis} and Trevathan, {James K.} and Ross, {Erika K.} and Bartoletta, {John J.} and Park, {Hyung Ook} and Paek, {Seungleal Brian} and Nicolai, {Evan N.} and Lee, {Jannifer H.} and Min, {Hoon Ki} and Kimble, {Christopher J.} and Blaha, {Charles D.} and Bennet, {Kevin E.}",
note = "Funding Information: This work was supported by the National Institutes of Health NINDS (R01 NS75013, R01 NS70872 awards to KHL, and R01 NS084975 award to JLL), and The Grainger Foundation. The authors gratefully acknowledge Bruce Knudsen, Andrea McConico, and Jill L. Anderson for their assistance with animal care and surgery, Drs. Jan T. Hachmann and Grant W. Mallory for their assistance with animal surgery and data collection, Drs. Peter J. Grahn and Aldo A. Mendez, and Anders J. Asp for their assistance with data collection, Megan L. Settell for her assistance with electrode manufacturing, Malcolm Mcintosh, Diane Eaker, Kenneth R. Kressin, Joshua B. Boesche, Sidney V. Whitlock, and their colleagues of the Mayo Clinic Division of Engineering for their contribution to the development and testing of the WINCS Harmoni device and WincsWare software development, Dr. Barry Gilbert, Rick Philpott, James Humble, Christopher Felton, of the Mayo Clinic Special Purpose Processor Development Group for the design of the delta-sigma analog-to-digital converter integrated circuit, and Dr. Penelope Duffy and Dr. Kip Ludwig for providing helpful advice on this manuscript. Publisher Copyright: {\textcopyright} The Author(s) 2017.",
year = "2017",
doi = "10.1038/srep46675",
language = "English (US)",
volume = "7",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}