Nest#4-Nerve Excitation Control Through AC Regulation (NECTAR)

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Control of physiological systems via the autonomic nervous system is often based on a baseline of tonic neural activity that is modulated to achieve a desired state. Electrical stimulation can be used to increase, or upregulate, this activity, but until recently, there was no reliable means to rapidly and reversibly decrease, or downregulate, this activity. The ability to downregulate, or completely block, neural activity could apply to a wide range of clinical applications and new treatments, including: downregulation of sympathetic drive to the heart for arrhythmias, block of bronchopulmonary parasympathetic nerves to reverse the bronchospasm in chronic obstructive pulmonary disease (COPD), block of nociceptive fibers to alleviate chronic neuropathic pain, and block of spastic urinary sphincter muscles to enable voiding, etc. Kilohertz frequency alternating current (KHFAC) has been demonstrated as a way to provide nerve block in a quick acting, titratable, and rapidly reversible manner. The goal of the NECTAR project is to create the tools necessary to allow researchers to incorporate reversible electrical nerve block via KHFAC into their research in a practical, effective, and safe manner. KHFAC nerve block has two key features that distinguish it from non-electrical nerve block. First, KHFAC nerve block occurs instantly. Second, KHFAC nerve block is fully and rapidly reversible. Unfortunately, research in the area of nerve block has been hampered by a lack of commercially available nerve block devices. Successful application of KHFAC block requires knowledge of the specific waveform parameters for effective and safe use of these waveforms in neural control. The therapeutic effect of KHFAC is complex and multimodal resulting in suboptimal results from improperly tuned waveform parameters. The contribution of the NECTAR project will be to provide two critical deliverables related to KHFAC block: 1) a fully featured device with reproducible outputs and 2) comprehensive mapping of the KHFAC parameter space. In aim one, a KHFAC module will be produced that will include many key features such as amplitude/ frequency ramping, validated outputs, DC offset mitigation, and charge injection capacity (CIC) electrode testing. In aim two, we will perform chronic in vivo studies to provide data that establishes the therapeutic window for KHFAC block with respect to frequency, amplitude, charge delivery, and duty cycle. These studies will involve both functional and histological metrics for safety and efficacy. Electrical block, when combined with electrical stimulation, can provide real-time control of neural activity, in which action potentials can be variably upregulated or downregulated as needed; a significant advantage for many bioelectronic applications. With the completion of Aims 1 and 2, the NECTAR project will enable the bioelectronic research community to rapidly proceed with incorporation of KHFAC electrical nerve block into their research studies.