The primary objective of this investigation is to address the limitations of currently available first generation functional electrical stimulation (FES) systems for standing after spinal cord injury by a) activating a greater portion of the targeted muscles to increase available knee extension moment and b) selectively recruiting synergistic muscles to offset fatigue. We will accomplish this through the innovative application of nerve-based cuff electrodes in a series of translational research studies designed to build upon existing animal work and safely and efficiently introduce them into human clinical trials. All current implanted FES systems for standing utilize muscle-based stimulating electrodes that only partially activate the available motor unit pool. While more than adequate for smaller and lighter implant recipients, this approach yields insufficient knee extension moment for heavier or taller candidates. Such individuals require more complete activation of the quadriceps to achieve acceptable functional standing, while simultaneously avoiding the counterproductive hip flexion caused by the femorally innervated sartorius and rectus femoris. The first goal of this study is to demonstrate the feasibility of utilizing stimulating nerve cuff electrodes in standing neuroprostheses, and thus extend the potential user population to individuals who currently cannot take advantage of the technology due to their size and weight. The proximal femoral nerve trunk is composed of numerous fascicles serving structures both advantageous and counterproductive to stable upright standing. Animal studies have demonstrated that a stimulating nerve cuff placing multiple contacts around the nerve can selectively activate individual fascicles within the nerve. The second goal of this investigation is to generate a realistic model of cuff-nerve geometry and determine the fascicular selectivity of multi-contact cuff electrodes on the multi-fascicular human femoral nerve via computer simulation analyses. This will result in an optimized cuff design that maximizes selectivity without detailed a prior knowledge, and thus suitable for clinical use. The third and final goal of this project is to establish the acute and chronic performance of multi-contact cuff electrodes in vivo in human volunteers. Intermittent and cyclic stimulation to individual contacts of chronically implanted electrodes on the distal peripheral nerve branches innervating the vastus lateralis and intermedius will allow fibers to rest while maintaining a constant net submaximal joint moment, effectively increasing duty cycle and allowing some recovery from fatigue. Selectivity of multi-contact nerve cuff electrodes on the proximal femoral nerve will be established in a series of acute intra-operative tests. Completion of this project will extend the functionality of existing neuroprostheses and provide immediate benefit to current system users. It will expand the potential user population, improve consistency of standing performance across individuals, and delay the effects of fatigue. Selective activation of individual muscles from a single multi-contact cuff electrode around a multi-fascicular nerve trunk will simplify the surgical installation of systems that provide more advanced functions such as stepping and stair climbing. Thus, in addition to their immediate impact on the functionality and performance of standing systems, the proposed studies will build a foundation for future developments in lower extremity neuroprostheses by selectively activating the appropriate fascicles in the proximal femoral nerve trunk.