{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T21:53:09Z","timestamp":1790027589539,"version":"4.0.1"},"reference-count":86,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000406","name":"Motor Neurone Disease Association","doi-asserted-by":"publisher","award":["MR\/K01014X\/1"],"award-info":[{"award-number":["MR\/K01014X\/1"]}],"id":[{"id":"10.13039\/501100000406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 NS105479"],"award-info":[{"award-number":["R01 NS105479"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["172123"],"award-info":[{"award-number":["172123"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","award":["4365"],"award-info":[{"award-number":["4365"]}],"id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000971","name":"ALS Association","doi-asserted-by":"publisher","award":["2015"],"award-info":[{"award-number":["2015"]}],"id":[{"id":"10.13039\/100000971","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Understanding the presymptomatic biology in those at high risk of developing amyotrophic lateral sclerosis (ALS) is essential for the development of preventative therapeutic interventions. Approximately 10% of ALS is associated with a <jats:italic>C9orf72<\/jats:italic> expansion or pathogenic variants in <jats:italic>SOD1<\/jats:italic>. Magnetoencephalography (MEG), combined with machine learning algorithms, can model brain network dynamics in such at\u2010risk populations to develop pathogenic biomarkers. Individuals with symptomatic ALS (symALS, <jats:italic>n<\/jats:italic>\u2009=\u200961), asymptomatic <jats:italic>C9orf72<\/jats:italic> carriers (aC9, <jats:italic>n<\/jats:italic>\u2009=\u200916), or pathological <jats:italic>SOD1<\/jats:italic> carriers (aSOD, <jats:italic>n<\/jats:italic>\u2009=\u200912), and healthy controls (<jats:italic>n<\/jats:italic>\u2009=\u200984) underwent resting\u2010state MEG recordings. Extracted metrics included regional oscillatory power, connectivity, and spectral shape. \u2018DyNeMo\u2019 was trained to identify six functional dynamic brain networks. Metrics were compared between groups. A classifier was trained to distinguish asymptomatic gene carriers from controls. Compared to controls, beta frequency power was decreased in both symALS and aC9 groups. The aC9 group showed a marked slowing of frontal oscillatory activity, while the aSOD group showed a marked acceleration. Dynamic network coactivation was dramatically disrupted in aC9, more than in both symALS and aSOD. The classifier accurately distinguished genetically at\u2010risk groups from controls (receiver\u2010operator\u2010characteristic area\u2010under\u2010curve 0.89). The cerebral network dynamics of aC9 are markedly different from both aSOD and symALS, supporting the concept of profoundly different upstream pathways in <jats:italic>SOD1<\/jats:italic> ALS, sparing wider cortical pathology when compared to <jats:italic>C9orf72<\/jats:italic> ALS. aC9 changes may reflect chronic adaptive changes relating to neurodevelopmental factors or underpin aspects of system vulnerability that define penetrance variability. MEG metrics might provide important biomarkers of prevention therapy efficacy and phenoconversion in at\u2010risk populations.<\/jats:p>","DOI":"10.1002\/hbm.70345","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T12:54:18Z","timestamp":1759496058000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Divergent Brain Network Activity in Asymptomatic <i>C9orf72<\/i> and <i>SOD1<\/i> Variant Carriers Compared With Established Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-6156","authenticated-orcid":false,"given":"Michael","family":"Trubshaw","sequence":"first","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-1207","authenticated-orcid":false,"given":"Chetan","family":"Gohil","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Department of Psychiatry University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Edmond","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0774-4366","authenticated-orcid":false,"given":"Malcolm","family":"Proudfoot","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Yoganathan","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Wuu","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Miami  Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Northall","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Kohl","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Department of Psychiatry University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Stagg","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna C.","family":"Nobre","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Department of Psychiatry University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Talbot","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander G.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Benatar","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Miami  Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Woolrich","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Department of Psychiatry University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin R.","family":"Turner","sequence":"additional","affiliation":[{"name":"Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging University of Oxford  Oxford UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26476"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.103199"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2019.1587634"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311\u2010022\u201001237\u20104"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25276"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab404"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.4266"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2014.00127"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.03.071"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195\u2010021\u201000772\u20100"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2020.1087"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2307\/2531595"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol\u20102021\u2010002989"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010020\u201000744\u2010x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.16201"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24740"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.70275"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2022.2101379"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.10.014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.06.078"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2015.1872"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12021\u2010022\u201009581\u20108"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2023.2236651"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91949"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119595"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2022.102965"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.96.15_supplement.2244"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/11866763_8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51114"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010023\u201000553\u20106"},{"key":"e_1_2_9_33_1","unstructured":"Kohl O. M.Woolrich A. C.Nobre andA.Quinn.2023.\u201cGlasser52: A Parcellation for MEG\u2010Analysis.\u201dZenodo.https:\/\/doi.org\/10.5281\/zenodo.10401793."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29378"},{"key":"e_1_2_9_35_1","unstructured":"Larson E. A.Gramfort D. A.Engemann et\u00a0al.2024.\u201cMNE\u2010Python.\u201d(Version v1.6.1) [Computer Software]. Zenodo.https:\/\/doi.org\/10.5281\/zenodo.10519948."},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25748"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2016.12.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010024\u201012743\u20100"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21147"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(12)70043\u20101"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaa076"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2021.03.002"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102015\u2010311945"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.26536"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1159\/000086353"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2022.2152696"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004393"},{"key":"e_1_2_9_49_1","first-page":"2825","article-title":"Scikit\u2010Learn: Machine Learning in Python","volume":"12","author":"Pedregosa F.","year":"2011","journal-title":"Journal of Machine Learning Research"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201200"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11050549"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005333"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.23357"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2018.03.019"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25520"},{"key":"e_1_2_9_56_1","unstructured":"Quinn A. J.2023.\u201cGolmtools.\u201dGitLab.https:\/\/gitlab.com\/ajquinn\/glmtools."},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00082"},{"key":"e_1_2_9_58_1","unstructured":"Quinn A. J. M. W. J.vanEs C.Gohil andM. W.Woolrich.2023.\u201cOHBA Software Library in Python (OSL).\u201d(Version 0.2.0) [Python].https:\/\/doi.org\/10.5281\/zenodo.6875060."},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2011.12.013"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22547"},{"key":"e_1_2_9_61_1","unstructured":"SciPy.2025.\u201cFundamental Algorithms for Scientific Computing in Python.\u201dhttps:\/\/scipy.org\/."},{"key":"e_1_2_9_62_1","doi-asserted-by":"crossref","unstructured":"Sevelsted St\u00e6rmose T. L. M.Andersen S. S.Dalal C. J.Bailey andJ. U.Blicher.2022.\u201cMovement\u2010Related Beta Modulation in Amyotrophic Lateral Sclerosis Depends on Muscle Strength: A Magnetoencephalography Study.\u201dNeurology.https:\/\/doi.org\/10.1101\/2022.09.28.22280359.","DOI":"10.1101\/2022.09.28.22280359"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.08.028"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2008.527"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51989"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm034"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/21678421.2016.1267768"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.3390\/e22020239"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1109\/TSP.2005.853302"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2011.11.017"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1093\/braincomms\/fcae164"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2025.2110823"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh509"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.3109\/17482968.2011.636050"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02534144"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awad120"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)31287\u20104"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26572"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2008.01.011"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn071"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1109\/TAU.1967.1161901"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102018\u2010318994"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2022.102397"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010009\u20100078\u20100"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2014.01.060"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.04.041"},{"key":"e_1_2_9_87_1","doi-asserted-by":"crossref","unstructured":"Yoganathan K. M.Trubshaw O.Kohl et\u00a0al.2025.\u201cReduced Beta Bursting Underpins Loss of Corticomuscular Coherence in Amyotrophic Lateral Sclerosis.\u201dBrain Communications.","DOI":"10.1093\/braincomms\/fcaf339"}],"container-title":["Human Brain Mapping"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hbm.70345","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T01:16:20Z","timestamp":1760404580000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hbm.70345"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":86,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1002\/hbm.70345"],"URL":"https:\/\/doi.org\/10.1002\/hbm.70345","archive":["Portico"],"relation":{},"ISSN":["1065-9471","1097-0193"],"issn-type":[{"value":"1065-9471","type":"print"},{"value":"1097-0193","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"2024-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70345"}}