Systems/Circuits A Computational Model for Epidural Electrical Stimulation of Spinal Sensorimotor Circuits

Epidural electrical stimulation (EES) of lumbosacral segments can restore a range of movements after spinal cord injury. However, the mechanisms and neural structures through which EES facilitates movement execution remain unclear. Here, we designed a computa-tional model and performed in vivo experiments to investigate the type of fibers, neurons, and circuits recruited in response to EES. We first developed a realistic finite element computer model of rat lumbosacral segments to identify the currents generated by EES. To evaluate the impact of these currents on sensorimotor circuits, we coupled thismodel with an anatomically realistic axon-cablemodel of motoneurons, interneurons, andmyelinated afferent fibers for antagonistic anklemuscles. Comparisons between computer simulations and experiments revealed the ability of the model to predict EES-evoked motor responses over multiple intensities and locations. Analysis of the recruitedneural structures revealed the lackofdirect influenceofEESonmotoneuronsand interneurons. Simulations and pharmacological experiments demonstrated that EES engages spinal circuits trans-synaptically through the recruitment of myelinated afferent fibers. Themodel also predicted the capacity of spatially distinct EES tomodulate side-specific limbmovements and, to a lesser extent, extension versus flexion. These predictions were confirmed during standing and walking enabled by EES in spinal rats. These combined results provide a mechanistic framework for the design of spinal neuroprosthetic systems to improve standing and walkin