WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

• Published in: Scientific reports Vol. 7; no. 1; p. 46675
• Main Authors: Lee, Kendall H., Lujan, J. Luis, Trevathan, James K., Ross, Erika K., Bartoletta, John J., Park, Hyung Ook, Paek, Seungleal Brian, Nicolai, Evan N., Lee, Jannifer H., Min, Hoon-Ki, Kimble, Christopher J., Blaha, Charles D., Bennet, Kevin E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28-04-2017; Nature Publishing Group
• Subjects: 119/118; 631/378/1689; 631/378/2632/1663; 631/378/2632/2634; 639/166/985; 692/308/575; Animal models; Animals; Biosensing Techniques - methods; Brain; Brain - metabolism; Brain - physiology; Brain Diseases - diagnosis; Brain Diseases - metabolism; Brain Diseases - physiopathology; Brain research; Clinical trials; Cognitive ability; Deep brain stimulation; Deep Brain Stimulation - methods; Dopamine - metabolism; Electric Stimulation; Electrochemical Techniques - methods; Feedback; Female; Humanities and Social Sciences; Humans; Macaca mulatta; Male; Mice; multidisciplinary; Neuromodulation; Neurotransmitter Agents - metabolism; Neurotransmitters; Precision medicine; Rats, Sprague-Dawley; Science; Swine; Telemetry - methods; Therapeutic applications
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep46675

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.