{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T03:50:26Z","timestamp":1781927426590,"version":"3.54.5"},"posted":{"date-parts":[[2026,6,17]]},"group-title":"Neurology","reference-count":73,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T00:00:00Z","timestamp":1781654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"NIH","award":["KL2TR002346"],"award-info":[{"award-number":["KL2TR002346"]}]},{"name":"NIH","award":["UL1TR002345"],"award-info":[{"award-number":["UL1TR002345"]}]},{"name":"NIH","award":["NS125863"],"award-info":[{"award-number":["NS125863"]}]},{"name":"NIH","award":["P30CA091842"],"award-info":[{"award-number":["P30CA091842"]}]},{"name":"DOD","award":["HT9425-24-1-0580"],"award-info":[{"award-number":["HT9425-24-1-0580"]}]},{"DOI":"10.13039\/100007338","name":"Foundation for Barnes-Jewish Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007338","id-type":"DOI","asserted-by":"crossref"}]},{"name":"McDonnell Center for Systems Neuroscience at Washington University in St. Louis"},{"name":"Longer Life Foundation: An RGA\/Washington University Collaboration"},{"name":"European Research Council","award":["101045605"],"award-info":[{"award-number":["101045605"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Central nervous system injury causes motor deficits through derangement of excitatory, inhibitory, and\/or neuromodulatory inputs to motoneurons, the three fundamental components of motor commands. Typically, study of pathologic neural control in humans is restricted to only one of the three. Chardon et al. (2024) presented a fundamentally new approach to comprehensively study all components by reverse engineering motor unit firing patterns. We apply their framework to motor unit firing patterns from 89 people with multiple sclerosis (MS) and 34 controls to study excitatory, inhibitory, and neuromodulatory contributions to pathologic motor output. Disruptions to all components are plausible in MS, a disease hallmarked by heterogeneity in nearly all aspects. Accordingly, we found abnormalities in MS for all three components. Notably, neuromodulation included both high and low extremes. Our results suggest that pathophysiology of motor commands in MS varies among patients, a finding fundamentally different from other studied populations showing relative consistency.<\/jats:p>","DOI":"10.64898\/2026.06.15.26355613","type":"posted-content","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T01:05:25Z","timestamp":1781744725000},"source":"Crossref","is-referenced-by-count":0,"title":["Reverse engineering of motor unit discharge in multiple sclerosis reveals heterogeneity of voluntary motor commands"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8228-0525","authenticated-orcid":false,"given":"Laura M.","family":"McPherson","sequence":"first","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO"},{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7643-3887","authenticated-orcid":false,"given":"Keith R.","family":"Lohse","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO"},{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Skyler M.","family":"Simon","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0002-9255","authenticated-orcid":false,"given":"Daniel B.","family":"Free","sequence":"additional","affiliation":[{"name":"Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2288-8672","authenticated-orcid":false,"given":"James A.","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9094-8932","authenticated-orcid":false,"given":"Francesco","family":"Negro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences, Universita degli Studi di Brescia, Brescia, IT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0520-4283","authenticated-orcid":false,"given":"Robert T.","family":"Naismith","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0829-7569","authenticated-orcid":false,"given":"Anne H.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Neurology, Washington University School of Medicine, St. Louis, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061919550870000_2026.06.15.26355613v1.1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"2026061919550870000_2026.06.15.26355613v1.2","doi-asserted-by":"crossref","first-page":"016007","DOI":"10.1088\/1741-2552\/ac4594","article-title":"A computational approach for generating continuous estimates of motor unit discharge rates and visualizing population discharge characteristics","volume":"19","year":"2022","journal-title":"J Neural Eng"},{"key":"2026061919550870000_2026.06.15.26355613v1.3","doi-asserted-by":"crossref","first-page":"016034","DOI":"10.1088\/1741-2552\/acb1d7","article-title":"A geometric approach to quantifying the neuromodulatory effects of persistent inward currents on individual motor unit discharge patterns","volume":"20","year":"2023","journal-title":"J Neural Eng"},{"key":"2026061919550870000_2026.06.15.26355613v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(81)90208-6"},{"key":"2026061919550870000_2026.06.15.26355613v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0713-0_25"},{"key":"2026061919550870000_2026.06.15.26355613v1.6","unstructured":"Binder MD , Heckman CJ & Powers RK (2011). 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