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Whether these alterations in sleep macroarchitecture are associated with \u2014 or even precede \u2014 abnormalities in sleep-related EEG features remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Here, we characterize sleep microarchitecture using polysomnography for patients with ALS (\n                      <jats:italic>n<\/jats:italic>\n                      = 33) and controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 32) as well as for asymptomatic carriers of superoxide dismutase 1 (\n                      <jats:italic>SOD1<\/jats:italic>\n                      ) or\n                      <jats:italic>C9ORF72<\/jats:italic>\n                      mutations (\n                      <jats:italic>n<\/jats:italic>\n                      = 57) and noncarrier controls (\n                      <jats:italic>n<\/jats:italic>\n                      = 30). Patients and controls with factors that could confound sleep structure, including respiratory insufficiency, were prospectively excluded. The results were complemented in 3 ALS mouse models (\n                      <jats:italic>Sod1<\/jats:italic>\n                      <jats:sup>G86R<\/jats:sup>\n                      ,\n                      <jats:italic>Fus<\/jats:italic>\n                      <jats:sup>\u0394NLS\/+<\/jats:sup>\n                      , and\n                      <jats:italic>TDP-43<\/jats:italic>\n                      <jats:sup>Q331K<\/jats:sup>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We observed a brain-wide reduction in the density of sleep spindles, slow oscillations, and K-complexes in patients with early-stage ALS and in presymptomatic gene carriers. These defects in sleep spindles and slow oscillations correlated with cognitive performance in both cohorts, particularly with scores on memory, verbal fluency, and language function. Alterations in sleep microarchitecture were replicated in 3 mouse models, and decreases in sleep spindles were rescued following intracerebroventricular supplementation of melanin-concentrating hormone (MCH) or by oral administration of a dual orexin receptor antagonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Sleep microarchitecture was associated with cognitive deficits and causally linked to aberrant MCH and orexin signaling in ALS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>Agence Nationale de la Recherche (ANR); Fondation Thierry Latran; Association Francaise de Recherche sur la scl\u00e9rose lat\u00e9rale amyotrophique; Association Fran\u00e7aise contre les myopathies; TargetALS; and Joint Program on Neurodegenerative Diseases Research (JPND).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci194555","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T17:00:26Z","timestamp":1762448426000},"source":"Crossref","is-referenced-by-count":6,"title":["Early brain-wide disruption of sleep microarchitecture in amyotrophic lateral sclerosis"],"prefix":"10.1172","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2953-7157","authenticated-orcid":true,"given":"Christina","family":"Lang","sequence":"first","affiliation":[{"name":"Department of Neurology, University Hospital of Ulm, Ulm, Germany."},{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE), Ulm, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1623-7091","authenticated-orcid":true,"given":"Simon J.","family":"Guillot","sequence":"additional","affiliation":[{"name":"University of Strasbourg, INSERM, Strasbourg Translational 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