The network of peripheral nerves offers extraordinary potential for modulating and/or monitoring the functioning of internal organs or the brain. The nervous system functions by generating patterns of neural activity. To influence neural activity for desired outcomes, neural interface technology must access the appropriate peripheral nerve tissue, activate it in a focal targeted manner, and alter the patterns of activity. The anatomical organization of peripheral nerves, which consists of multiple nerve fibers clustered into one or more fascicles, presents opportunities and challenges for precise control of spatiotemporal patterns. The efficacy of peripheral nerve stimulation will depend greatly on the ability of the bioelectronic interface to achieve the specificity that may be required for clinical applications, basic science studies and for augmentation of human capabilities. Systems that enable greater specifictty are likely to achieve a higher degree of functionality with fewer side effects. This work is directed at increasing the specificity that can be achieved with peripheral nerve stimulation in a manner that will enable a wide range of clinical and non­ clinical applications. lntraneural electrodes that are embedded within the fascicles can utilize low-amplitude electrical pulses to generate an electric field that can preferentially activate small groups of fibers that are close to the electrode. Longitudinal intrafascicular electrodes (LIFEs) allow access to nerve fibers within a fascicle and their mechanical properties are well-suited for chronic use. LIFEs enable activation with sub­ fascicular specificity, but there is great potential for enhancing their specificity using advanced stimulation strategies. The goal of this US-French collaboration is to achieve high specificity by exploring two approaches: using multiple contacts within a fascicle to direct current (field-steering strategies) and using alternative shapes of stimulation pulses to preferentially activate fibers with specific properties (waveform strategies). The proposal builds on a prior collaboration in which a new hardware platform for stimulation was developed by the French team. Using computational models, we will develop and analyze new strategies for selective stimulation of nerve fibers within individual fascicles. The hardware platform will be enhanced and further developed to enable real-time implementation of the field-steering and waveform strategies with a set of LIFEs. In vivo studies on anesthetized rabbits will assess the ability of the field-steering and waveform strategies to enhance selectivity with intrafascicular stimulation.

Electrical stimulation technology for activating small groups of peripheral nerve fibers can form the foundation of bioelectronic systems to influence metabolic processes, enhance immune system function, regulate gastrointestinal activity, or treat a variety of medical conditions. This project will enhance the developing stimulation strategies that can selectively activate small of fibers that produce the desired clinical effect without producing undesirable side effects.