Mapping the Fascicular Anatomy of Human Sciatic Nerve to Inform Electrode Designs and Placement Locations to Improve Standing Neuroprostheses

1 Our ultimate objective is to help Veterans with spinal cord injuries (SCI) regain the ability to stand through 2 peripheral nerve stimulation (PNS), specifically targeting the sciatic nerve (SCN). Traditional standing 3 neuroprostheses aim to selectively activate nerves that control key muscles in the knee, hip, and trunk to 4 maintain standing. Independent activation of muscles in the lower limb with control algorithms paired with 5 sensory feedback further improves standing performance with such neuroprostheses. However, achieving 6 selective activation of the muscles innervated from the upper sciatic nerve has been historically proven to be 7 difficult. The neural fascicles that control multiple major muscle groups are all contained within the proximal SCN 8 (i.e., prior to their distal branching into discrete motor unit components). This makes it more difficult to individually 9 activate the hip extensor muscles, particularly the hamstrings, which are critical in positioning the mass of the 10 head, arms, trunk, and pelvis over the legs. To address this, our SPiRE award project has two main goals. First, 11 we plan to create a 3D model of the SCN fascicles, using microCT and histology techniques. Second, we will 12 characterize nerve and fiber morphology (using Histology) to inform electrode placement and design 13 approaches. This information will ultimately guide the design and surgical placement of new multi-contact nerve 14 cuff electrodes to improve the performance of standing neuroprostheses for SCI patients. During Aim 1, we will 15 develop a 3D model of the fascicles of the SCN, from sciatic notch to the distal branch points, using µCT 16 and histology. The spatial orientation between nerve fibers of the fascicles with respect to neural stimulation 17 electrode placement determines the functional performance of standing neuroprostheses. Hence the 18 development of a 3D model of SCN is crucial to computationally evaluate various electrode designs (electrode 19 geometry, placement, number of contacts and size of contacts) to ultimately achieve increased fiber recruitment, 20 and improved selectivity of fiber recruitment, of the hamstring muscles. During Aim 2, we will complete the 21 most comprehensive histological characterization of the proximal sciatic nerve performed to-date. We 22 will quantify the morphology of the SCN along the nerve at high-resolution. The output of this aim will be used to 23 a) inform the feasibility of invasive electrode approaches, b) validate our fascicle morphology findings from 24 microCT, and c) establish the parameters required to create accurate computational models in the future. Project Number: 1I21RX005151-01A1 | Fiscal Year: 2025 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Andrew Shoffstall | Institution: LOUIS STOKES CLEVELAND VA MEDICAL CENTER, CLEVELAND, OH | Activity Code: I21 | Study Section: Rehabilitation Research and Development SPiRE Program[RRDS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11053994