Electrodes for selective stimulation of the lateral spinal cord to restore sensation after lower-limb amputation - PROJECT SUMMARY/ABSTRACT Advances in design and actuation have led to dramatic improvements in prosthetic limbs. However, these devices cannot provide sensory feedback, which leads to slow gait and increased risk of falling. Recent evidence from our lab has shown that stimulation of lateral structures in the spinal cord and dorsal roots can effectively generate sensations in the distal limbs. In these studies, lateral SCS (LSCS) evoked sensations in regions of the amputated hands or feet, though many of these sensations also covered more proximal regions of the residual limb. To achieve more focal sensations in the missing limb will require development of electrodes with smaller contacts, tighter inter-contact spacing, and better arrangements than currently exist for SCS electrodes. Further, because the lateral epidural space is narrower and more curved than the traditional midline target of SCS, these novel SCS electrodes must be thinner and more flexible than existing SCS devices. Our long-term goal is to create a neurostimulation system to restore sensation by selectively stimulating lateral structures in the spinal cord. In this project, we will characterize how the DR respond to LSCS and optimize electrode design for stimulating these structures. Through a combination of large animal neurophysiology experiments, histological analyses, and computational modeling studies, we will characterize the selectivity of LSCS and design electrodes to maximize selectivity and achieve focal paresthetic coverage of the foot and ankle while avoiding injury to the underlying neural tissue. To achieve these goals, we will complete the following aims: Aim 1: Quantify functional organization of the lumbar DR and selectivity of LSCS. We will measure the selectivity of LSCS in cats by recording antidromic propagation of evoked action potentials in nerves throughout the hindlimb. We will also resect the dura and use hook electrodes to repeat these experiments while selectively stimulating individual DR to characterize their innervation patterns and somatotopic arrangement. Aim 2: Develop an anatomically-accurate computational model of the spinal cord, including the DR, and use that model as a platform to design LSCS electrodes. Utilizing high-resolution imaging data and microsurgical measurements of the human spinal cord, we will build a combined finite element and equivalent circuit model to simulate the anatomy and neurophysiology of lateral structures in the human spinal cord and their response to LSCS. We will use this platform to design the layout of electrode contacts on the LSCS device and stimulation configurations and waveforms to maximize selectivity of stimulation of individual DR. Aim 3: Perform large animal surgeries to optimize the mechanical properties of the LSCS electrode substrate to avoid neural damage and maintain chronic stability of electrode placement. In pigs, we will chronically implant LSCS electrodes with multiple different mechanical substrate designs, including varying the cross-section of the device and any tooling that may aide in insertion and stabilization of the device. We will perform histological analysis to characterize tissue damage and the relationship between mechanical properties and tissue injury.