PROJECT SUMMARY There is a large and growing population of amputees whose needs are not being fully met by current prosthetic hand technology, which results in reduced quality of life. The long-term goal of the proposed work is based on the notion that prosthetic hand technology that can provide task-related sensations to the residual limb of an amputee will increase their proficiency in sensorimotor tasks and therefore allow them to participate in a greater range of employment and leisure activities. The Adaptive Neural Systems neural-enabled prosthetic hand (ANS-NEPH) system was designed and developed by our lab in collaboration with industrial and clinical partners to provide amputees with task-relevant sensations. The system uses signals derived from sensors on an instrumented prosthetic hand to elicit sensations by delivering stimulation via fine-wire longitudinal intrafascicular electrodes (LIFEs) implanted in peripheral nerves of the residual limb. A commercially proven neural stimulation technology from Cochlear Ltd. was re- engineered to interface with neural structures in the peripheral nerves with LIFEs. In the proposed project, we will continue a longitudinal first-in-human clinical trial to evaluate clinical safety and device functionality Four subjects will be enrolled to participate in this long-term study. Each subject will have the implanted components surgically installed, be fitted with the external components of the system, participate in an extensive series of experiments designed to assess long-term viability of our approach, and use it on a daily basis as their primary prosthetic hand. The primary outcome of this work will be a demonstration of clinical feasibility of a neural-enabled prosthetic hand system for daily use at home (for approximately two years) or at the workplace that uses wirelessly- controlled implantable stimulation technology. For transradial amputees, real-time sensation is likely to improve sensorimotor capabilities; everyday use is likely to enhance embodiment of the prosthesis by the user. Furthermore, stimulation of afferent fibers may also reduce the severity and incidence of phantom limb pain. This system will constitute the next generation of prosthetic hand technology for transradial amputees and will form the foundation for systems to be developed that can provide sensation to other upper limb amputees (transhumeral, shoulder disarticulation). Finally, the deployment and chronic use of an implantable system that enables stimulation of discrete sets of small groups of afferent fibers may pave the way for future uses of this technology to activate peripheral nerves that may influence metabolic processes, enhance immune system function, regulate gastrointestinal activity, or treat a variety of medical conditions.