Despite the long-term promise of stem-cell and other biological approaches, current options to improve function following spinal cord injury (SCI) remain quite limited. However, brain machine interfaces (BMIs) that use cortical activity to drive functional electrical stimulation (FES) of muscles or the spinal cord have great promise not only for the restoration of motor ability when using the BMI, but also for improved functional rehabilitation so that their performance is improved when the BMI is removed. The overall goal of our research is to identify strategies that maximize both of these potential strengths of cortically-controlled FES. A system using cortical activity to drive stimulation of individual muscles might maximize the restoration of motor function: by enabling users to vary the amplitude and timing of individual muscles, movements can potentially be adapted as necessary to achieve task demands. Alternate strategies of producing movement, such as activation of muscle groups or of sites in the spinal cord producing limb flexion or extension, will reduce the range of possible movements. Although these strategies might be simpler to learn after SCI than control of individual muscles, they clearly limit the level of motor function that can be restored. In order to achieve the greatest functional rehabilitation, however, spinal stimulation might be a more promising strategy than muscle stimulation. Repeated spinal stimulation might maintain the function of spinal pathways involved in the production of movement and enable restoration of connections from descending systems through associative plasticity. Conversely, since muscle stimulation does not activate spinal pathways to produce movement, it might produce less functional rehabilitation. There is therefore a potential tradeoff between muscle and spinal stimulation: muscle stimulation enables high levels of motor ability but might limit functional rehabilitation, while spinal stimulation might enhance rehabilitation but limit flexibility. Our research will investigate this tradeoff, with the goal of designing a hybrid system that combines spinal and muscle stimulation to achieve high levels of both motor ability and functional rehabilitation. We will perform these experiments in rats, implanting electrodes in the cortex to record neural activity and in the spinal cord and muscles to produce movements. We will then train rats to use these systems after SCI, evaluating whether they can improve motor ability and functional rehabilitation. In Aim 1, we will evaluate whether animals can produce high levels of motor ability with a system using cortical activity to control activation of individual muscles. In Aim 2, we will evaluate whether animals using cortical activity to control activation of spinal...