{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:14:58Z","timestamp":1784121298813,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000764","name":"King's College London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000764","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder of motor neurons, carrying a short survival.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>High\u2010density motor unit recordings permit analysis of motor unit size (amplitude) and firing behaviour (afterhyperpolarization duration and muscle fibre conduction velocity).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Serial recordings from biceps brachii indicated that motor units fired faster and with greater amplitude as disease progressed.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>First\u2010recruited motor units in the latter stages of ALS developed characteristics akin to fast\u2010twitch motor units, possibly as a compensatory mechanism for the selective loss of this motor unit subset.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This process may become maladaptive, highlighting a novel therapeutic target to reduce motor unit vulnerability.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with a median survival of 3 years. We employed serial high\u2010density surface electromyography (HDSEMG) to characterize voluntary and ectopic patterns of motor unit (MU) firing at different stages of disease. By distinguishing MU subtypes with variable vulnerability to disease, we aimed to evaluate compensatory neuronal adaptations that accompany disease progression. Twenty patients with ALS and five patients with benign fasciculation syndrome (BFS) underwent 1\u20137 assessments each. HDSEMG measurements comprised 30\u00a0min of resting muscle and 1\u00a0min of light voluntary activity from biceps brachii bilaterally. MU decomposition was performed by the progressive FastICA peel\u2010off technique. Inter\u2010spike interval, firing pattern, MU potential area, afterhyperpolarization duration and muscle fibre conduction velocity were determined. In total, 373 MUs (ALS\u00a0=\u00a0287; BFS\u00a0=\u00a086) were identified from 182 recordings. Weak ALS muscles demonstrated a lower mean inter\u2010spike interval (82.7\u00a0ms) than strong ALS muscles (96.0\u00a0ms; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.00919) and BFS muscles (95.3\u00a0ms; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0039). Mean MU potential area (area under the curve: 487.5 <jats:italic>vs<\/jats:italic>. 98.7\u00a0\u03bcV ms; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) and muscle fibre conduction velocity (6.2 <jats:italic>vs<\/jats:italic>. 5.1\u00a0m\/s; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.0292) were greater in weak ALS muscles than in BFS muscles. Purely fasciculating MUs had a greater mean MU potential area than MUs also under voluntary command (area under the curve: 679.6 <jats:italic>vs<\/jats:italic>. 232.4 \u03bcV ms; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.00144). These results suggest that first\u2010recruited MUs develop a faster phenotype in the latter stages of ALS, likely driven by the preferential loss of vulnerable fast\u2010twitch MUs. Inhibition of this potentially maladaptive phenotypic drift may protect the longevity of the MU pool, stimulating a novel therapeutic avenue.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp281310","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T23:22:13Z","timestamp":1626304933000},"page":"4117-4130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["First\u2010recruited motor units adopt a faster phenotype in amyotrophic lateral sclerosis"],"prefix":"10.1113","volume":"599","author":[{"given":"Thomas","family":"Weddell","sequence":"first","affiliation":[{"name":"UK Dementia Research Institute Department of Basic and Clinical Neuroscience Maurice Wohl Clinical Neuroscience Institute Institute of Psychiatry Psychology and Neuroscience King's College London  London 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