An Integrated Neurochemical/Electrophysiological Recording and Neuromodulation System for Basic and Clinical Research

PROJECT SUMMARY WINCS International LLC, in partnership with Mayo Clinic, proposes to develop and demonstrate a highly innovative next-generation clinical instrument together with custom user-friendly display and analysis software. For the first time, the Multifunctional Apparatus for Voltammetry, Electrophysiology, and Neuromodulation (MAVEN) will offer wireless voltammetric sensing of multiple neurotransmitters (e.g., dopamine, serotonin, and adenosine) at carbon-fiber microelectrodes. MAVEN can be applied to a broad range of clinical neuroscience research subjects involving brain neurosurgeries. Alongside these multiple neurochemical sensing capabilities, the device will be capable of near-simultaneous electrophysiological (e.g., action and local field potentials) recordings. The main innovation of the MAVEN system is to include state-of-the-art voltammetric techniques to quantitatively measure both phasic (stimulation-induced) and tonic (resting) concentration levels of neurochemicals in real-time and near-simultaneously with other recording modalities. This capability is currently unavailable in clinical neuroscience research. In addition, multiple cyclic square wave voltammetry (MCSWV) will enable second-to-second quantitative measurements of tonic extracellular levels of dopamine and serotonin with exceptional spatial resolution, sensitivity, specificity, and minimal tissue disturbance. This proposal employs our unique combined expertise in neuroscience, electrochemistry, engineering, and software development to validate this novel clinical research instrument in preparation for its use during intraoperative clinical neurosurgeries. Also, combining electrophysiology and electrochemical technologies would enable investigators to probe unexplored links between the abnormal activity of neural elements and the dopaminergic, serotonergic, purinergic (adenosine) dynamics associated with neuropsychopathologies, such as Parkinson’s disease, essential tremor, obsessive-compulsive disorder, depression, and epilepsy. Our large animal model (swine) studies emulating existing human intraoperative neurosurgical procedures will provide essential information to guide and inform the finalization of the MAVEN design for use by the clinical neuroscience community in future IDE-enabled mechanistic clinical studies. Our proposal seeks to (1) finalize the development of MAVEN, together with a sophisticated user-friendly software interface that (2) meets device manufacturing processes, regulatory Design Control, and medical safety requirements to obtain an FDA-approved Investigational Device Exemption (IDE), and (3) use a swine model to develop MAVEN stimulation and recording protocols for use in existing intraoperative neurosurgical procedures (e.g., deep brain stimulation neurosurgeries and cortical lobectomies). This includes demonstrating the functionality, versatility, and efficacy of the MAVEN system for future pre-clinical and clinical neuroscience research.PROJECT NARRATIVE The proposed studies consist of three Aims in which, in Aim 1, WINCS International LLC, in partnership with Mayo Clinic Neural Engineering Laboratories and Division of Engineering, will finalize the development of a novel neurochemical/electrophysiological recording and stimulating instrument, called Multifunctional Apparatus for Voltammetry, Electrophysiology and Neuromodulation (MAVEN), together with a sophisticated user-friendly software interface, for a broad range of clinical neuroscience research in subjects undergoing intraoperative brain neurosurgeries. In Aim 2, overall development and construction plans for the MAVEN system will ensure that device manufacturing processes and design history files meet regulatory Design Control and medical safety requirements necessary to obtain approval for an FDA Investigational Device Exemption (IDE). Aim 3 is designed to integrate several MAVEN recording protocols into existing intraoperative clinical neurosurgical procedures (e.g., deep brain stimulation neurosurgeries and cortical lobectomies) using a large animal model (swine), including confirming MAVEN’s ability to reliably record neurochemical and electrophysiological events (e.g., dopamine, serotonin, and adenosine, and action/local field potential activity, respectively) for future use of the system in IDE-enabled mechanistic clinical studies.