{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T12:25:52Z","timestamp":1787401552088,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100001454","name":"American Epilepsy Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001454","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS110347"],"award-info":[{"award-number":["R01NS110347"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01NS116504"],"award-info":[{"award-number":["R01NS116504"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["T32NS096050"],"award-info":[{"award-number":["T32NS096050"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Although many patients with temporal lobe epilepsy achieve seizure freedom in the first post\u2010operative year, the likelihood of long\u2010term seizure freedom declines substantially over time. Late seizure relapse may reflect ongoing epileptogenicity, potentially driven by persistent epileptic activity arising from the epileptogenic zone. We hypothesized that its more distributed connectivity profile across brain networks would distinguish patients experiencing late relapse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We prospectively enrolled 209 patients with drug\u2010resistant temporal lobe epilepsy across six centers who underwent destructive surgery, pre\u2010operative diffusion\u2010weighted magnetic resonance imaging (MRI), and\/or\u00a0resting\u2010state functional MRI. To isolate network mechanisms related to late relapse rather than early surgical failure, we focused on patients who achieved seizure freedom after the first post\u2010operative year. After two post\u2010operative years, these patients were stratified into long\u2010term seizure freedom (SF\u2013SF) and late relapse (SF\u2013NSF). We delineated post\u2010operative resections to localize epileptogenic zones and quantified their network properties using graph\u2010theory metrics\u2013betweenness centrality and participation coefficient. Patient graph\u2010theory metrics were standardized relative to normative connectomes derived from 362 healthy controls. We evaluated associations between patient graph\u2010theory metrics and long\u2010term outcomes using Firth's bias\u2010reduced regressions and permutation testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fifty\u2010four patients with diffusion\u2010weighted MRI (SF\u2010SF\u2009=\u200937, SF\u2010NSF\u2009=\u200917) and 30 patients with functional MRI (SF\u2010SF\u2009=\u200919, SF\u2010NSF\u2009=\u200911) met the inclusion criteria. Greater functional MRI\u2010derived participation coefficient of resections was associated with late relapse, reflecting a more distributed connectivity profile across networks. In a post hoc analysis, lower diffusion\u2010weighted MRI\u2010derived betweenness centrality of the epileptogenic hippocampus was associated with late relapse. Effects were confirmed by patient\u2010level and anatomy\u2010preserving permutations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Long\u2010term outcomes in temporal lobe epilepsy depend not only on accurate localization and removal of epileptogenic tissue but also on how its connectivity is distributed across brain networks before surgery. Pre\u2010operative cross\u2010network connectivity of the epileptogenic zone may represent a biomarker of late relapse.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70441","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T11:40:48Z","timestamp":1787398848000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Distributed functional cross\u2010network connectivity of the epileptogenic zone predicts late seizure relapse in temporal lobe epilepsy"],"prefix":"10.1002","author":[{"given":"Victor","family":"Karpychev","sequence":"first","affiliation":[{"name":"Department of Neurology, School of Medicine Emory University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca W.","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Emory University  Atlanta Georgia 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