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Recent clinical studies have shown that epidural spinal cord stimulation may provide a beneficial adjunct for restoring lower extremity and other neurological functions. Herein, we review the recent clinical advances of lumbosacral epidural stimulation for restoration of sensorimotor function in individuals with motor complete SCI and we discuss the putative neural pathways involved in this promising neurorehabilitative approach. We focus on three main sections: review recent clinical results for locomotor restoration in complete SCI; discuss the contemporary understanding of electrical neuromodulation and signal transduction pathways involved in spinal locomotor networks; and review current challenges of motor system modulation and future directions toward integrative neurorestoration. The current understanding is that initial depolarization occurs at the level of large diameter dorsal root proprioceptive afferents that when integrated with interneuronal and latent residual supraspinal translesional connections can recruit locomotor centers and augment downstream motor units. Spinal epidural stimulation can initiate excitability changes in spinal networks and supraspinal networks. Different stimulation parameters can facilitate standing or stepping, and it may also have potential for augmenting myriad other sensorimotor and autonomic functions. More comprehensive investigation of the mechanisms that mediate the transformation of dysfunctional spinal networks to higher functional states with a greater focus on integrated systems-based control system may reveal the key mechanisms underlying neurological augmentation and motor restoration after severe paralysis.<\/jats:p>","DOI":"10.1152\/jn.00020.2021","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T16:21:06Z","timestamp":1634746866000},"page":"1843-1859","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":89,"title":["Epidural spinal cord stimulation as an intervention for motor recovery after motor complete spinal cord injury"],"prefix":"10.1152","volume":"126","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-6416","authenticated-orcid":true,"given":"Jan T.","family":"Hachmann","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Yousak","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury and Disorders Center, Hunter Holmes McGuire VAMC, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine J.","family":"Wallner","sequence":"additional","affiliation":[{"name":"Spinal Cord Injury and Disorders Center, Hunter Holmes McGuire VAMC, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parag N.","family":"Gad","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, University of California, Los Angeles, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V. 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