{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:11:12Z","timestamp":1791396672445,"version":"4.3.3"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007321","name":"Finding A Cure for Epilepsy and Seizures","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Sudden unexpected death in epilepsy (SUDEP) often follows generalized tonic\u2013clonic seizures during sleep, likely resulting from impaired brainstem cardiorespiratory function. We used ictal electrocardiogram (ECG)\u2010based cross\u2010frequency phase\u2013amplitude coupling (PAC) to detect cardiorespiratory disruptions, comparing SUDEP to non\u2010SUDEP cohorts. Leveraging respiratory modulation of ECG signals can provide a robust indirect proxy of respiratory monitoring despite high\u2010amplitude noise.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed ictal ECG and electroencephalographic recordings in 21 SUDEP cases and 21 non\u2010SUDEP epilepsy controls. Ictal ECG segments from 76 seizures (38 SUDEP, 38 non\u2010SUDEP) were processed using continuous wavelet transformation to compute PAC between respiratory (.1\u2013.55\u2009Hz, 6\u201333 breaths per minute) and cardiac (.7\u20133.7\u2009Hz, 42\u2013222 beats per minute) frequencies. Relative PAC coupling strength was evaluated for respiratory frequencies &gt; .25\u2009Hz (15 breaths per minute) and cardiac frequencies &gt;\u20091.7\u2009Hz (102 beats per minute). Furthermore, a 3\u2009\u00d7\u20093 grid of PAC ranges was derived for each 20\u2010s window, yielding 18 features (mean and SD) as inputs to a logistic regression model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Elevated ictal PAC at higher respiratory (&gt;.25\u2009Hz,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001) and cardiac (&gt;1.7\u2009Hz,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0142) frequencies in SUDEP patients suggests ictal respiration modulates ictal tachycardia, leading to cardiorespiratory dysfunction, probably brainstem\u2010mediated. The logistic model accurately distinguished 38 seizures in SUDEP cases from 38 seizures in non\u2010SUDEP cases (receiver operating characteristic area under the curve\u2009=\u200991%). Seizures in SUDEP patients had higher propensity scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.001) both per seizure and per patient. All six test seizures (three SUDEP, three non\u2010SUDEP) were correctly classified using the optimal threshold.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>Ictal ECG\u2010based PAC analysis is a potential noninvasive biomarker for SUDEP risk, capturing cardiorespiratory dysregulation during seizures. Its integration into wearable ECG devices could enable real\u2010time risk assessment, informing clinical interventions such as rescue medications, antiseizure medication adjustments, or surgical evaluations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70057","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T14:56:22Z","timestamp":1765637782000},"page":"1849-1860","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardiorespiratory cross\u2010frequency coupling biomarker for sudden unexpected death in epilepsy"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9178-5496","authenticated-orcid":false,"given":"Adam C.","family":"Gravitis","sequence":"first","affiliation":[{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1865-2280","authenticated-orcid":false,"given":"Richard","family":"Wennberg","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3339-8102","authenticated-orcid":false,"given":"Peter L.","family":"Carlen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario Canada"},{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"},{"name":"Department of Physiology University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3630-5423","authenticated-orcid":false,"given":"Yotin","family":"Chinvarun","sequence":"additional","affiliation":[{"name":"Comprehensive Epilepsy Program and Neurology Unit Phramongkutklao Hospital  Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-4361","authenticated-orcid":false,"given":"Victor","family":"Lira","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Laze","sequence":"additional","affiliation":[{"name":"Grossman School of Medicine New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0044-4632","authenticated-orcid":false,"given":"Orrin","family":"Devinsky","sequence":"additional","affiliation":[{"name":"Grossman School of Medicine New York University  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9969-4775","authenticated-orcid":false,"given":"Berj L.","family":"Bardakjian","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering University of Toronto  Toronto Ontario Canada"},{"name":"Edward S. 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