{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T13:09:35Z","timestamp":1778936975115,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS121145"],"award-info":[{"award-number":["R01NS121145"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002736","name":"Citizens United for Research in Epilepsy","doi-asserted-by":"publisher","award":["W81XWH\u201015\u20102\u20100069"],"award-info":[{"award-number":["W81XWH\u201015\u20102\u20100069"]}],"id":[{"id":"10.13039\/100002736","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM146611"],"award-info":[{"award-number":["T32GM146611"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT94252410116"],"award-info":[{"award-number":["HT94252410116"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Traumatic brain injury (TBI) can induce posttraumatic epilepsy (PTE), but early biomarkers for epileptogenesis are lacking. We aimed to investigate electrographic biomarkers before and during posttraumatic seizure development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used a repetitive diffuse TBI model in mice with continuous video\u2010EEG monitoring up to 4\u00bd\u2009months postinjury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty\u2010five percent of mice developed posttraumatic seizures (PTS) with highly variable latency (5\u2013126\u2009days postinjury). Most significantly, we identified fast ripple\u2010delta DOWN state coupling as an early biomarker that was detectable at 4\u2009days post\u2010TBI and appeared before seizure onset in all seizure\u2010experiencing mice. This EEG signature distinguished seizure\u2010experiencing from seizure\u2010free TBI mice with high specificity. Power spectrum analysis revealed elevated delta and theta power, reduced physiological fast oscillations (alpha, beta, gamma), and increased pathological high\u2010frequency oscillations (fast ripples) in seizure\u2010experiencing animals, indicating network hyperexcitability. Spike analysis showed that while TBI itself increased cortical excitability, seizure onset triggered a dramatic further interictal activity escalation. These electrographic signatures were remarkably consistent across all seizure\u2010experiencing animals regardless of single or recurrent seizure pattern.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Our results demonstrate that fast ripple\u2010delta coupling represents a promising early biomarker detectable at 4\u2009days post\u2010TBI, before seizure onset, offering potential for early identification of PTS susceptibility. Importantly, this biomarker identified all seizure\u2010prone animals regardless of whether they developed single or recurrent seizures, suggesting shared underlying mechanisms and clinical relevance for any PTS occurrence. These findings emphasize the utility of temporal EEG analysis for detecting early electrographic changes in posttraumatic epileptogenesis and may inform future intervention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Plain Language Summary<\/jats:title>\n                    <jats:p>Some people develop epilepsy after a traumatic brain injury, but it is currently impossible to predict who is at risk. Using mice, we found that a specific brain wave pattern, brief bursts of very fast electrical activity occurring during deep sleep, appeared within days after injury in animals that later developed seizures. This pattern was not seen in injured animals that remained seizure\u2010free. Detecting this early warning sign could help identify at\u2010risk individuals and enable earlier treatment to potentially prevent epilepsy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi4.70211","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T09:53:45Z","timestamp":1769594025000},"page":"409-421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fast ripple\u2010delta coupling as an early biomarker for post\u2010traumatic epileptogenesis in repetitive brain injury"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4447-3312","authenticated-orcid":false,"given":"Oleksii","family":"Shandra","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Florida International University  Miami Florida 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USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-0788","authenticated-orcid":false,"given":"Michael J.","family":"Benko","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery David Grant Medical Center  Travis AFB California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-9366","authenticated-orcid":false,"given":"Owen","family":"Leitzel","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental and Integrative Biology University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7211-826X","authenticated-orcid":false,"given":"Pritom Kumar","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Florida International University  Miami Florida 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