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For each subject, we used diffusion\u2010weighted magnetic resonance imaging to construct whole\u2010brain structural networks. First, we measured the extent of alterations by performing FBTCS\u2010negative (FBTCS\u2212) versus control and FBTCS\u2010positive (FBTCS+) versus control comparisons, thereby delineating altered subnetworks of the whole\u2010brain structural network. Second, by standardizing each patient's networks using control networks, we measured the subject\u2010specific abnormality at every brain region in the network, thereby quantifying the spatial localization and the amount of abnormality in every patient.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both FBTCS+ and FBTCS\u2212 patient groups had altered subnetworks with reduced fractional anisotropy and increased mean diffusivity compared to controls. The altered subnetwork in FBTCS+ patients was more widespread than in FBTCS\u2212 patients (441 connections altered at<jats:italic>t<\/jats:italic>\u00a0&gt;\u00a03,<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001 in FBTCS+ compared to 21 connections altered at<jats:italic>t<\/jats:italic>\u00a0&gt;\u00a03,<jats:italic>p<\/jats:italic>\u00a0=\u00a0.01 in FBTCS\u2212). Significantly greater abnormalities\u2014aggregated over the entire brain network as well as assessed at the resolution of individual brain areas\u2014were present in FBTCS+ patients (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001,<jats:italic>d<\/jats:italic>\u00a0=\u00a0.82, 95% confidence interval = .32\u20131.3). In contrast, the fewer abnormalities present in FBTCS\u2212 patients were mainly localized to the temporal and frontal areas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>The whole\u2010brain structural network is altered to a greater and more widespread extent in patients with TLE and FBTCS. We suggest that these abnormal networks may serve as an underlying structural basis or consequence of the greater seizure spread observed in FBTCS.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16819","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T19:59:22Z","timestamp":1611259162000},"page":"729-741","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Focal to bilateral tonic\u2013clonic seizures are associated with widespread network abnormality in temporal lobe epilepsy"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2090-4889","authenticated-orcid":false,"given":"Nishant","family":"Sinha","sequence":"first","affiliation":[{"name":"Faculty of Medical Sciences Translational and Clinical Research Institute Newcastle University Newcastle Upon Tyne UK"},{"name":"Computational Neuroscience, Neurology, and Psychiatry Lab Interdisciplinary 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Biomedical Research Centre University College London Queen Square Institute of Neurology London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8502-4487","authenticated-orcid":false,"given":"Sjoerd B.","family":"Vos","sequence":"additional","affiliation":[{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre University College London Queen Square Institute of Neurology London UK"},{"name":"Centre for Medical Image Computing University College London London UK"},{"name":"Neuroradiological Academic Unit University College London Queen Square Institute of Neurology University College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9395-1478","authenticated-orcid":false,"given":"Gavin P.","family":"Winston","sequence":"additional","affiliation":[{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre University College London Queen Square Institute of Neurology London UK"},{"name":"Epilepsy Society MRI Unit Chalfont St Peter UK"},{"name":"Division of Neurology Department of Medicine Queen\u2019s University Kingston ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-0681","authenticated-orcid":false,"given":"John S.","family":"Duncan","sequence":"additional","affiliation":[{"name":"National Institute for Health Research University College London Hospitals Biomedical Research Centre University College London Queen Square Institute of Neurology London UK"},{"name":"Epilepsy Society MRI Unit Chalfont St Peter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Computational Neuroscience, Neurology, and Psychiatry Lab Interdisciplinary Computing and Complex BioSystems Research Group School of Computing 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