{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T21:08:01Z","timestamp":1792012081706,"version":"4.4.0"},"reference-count":62,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Sudden unexpected death in epilepsy (SUDEP) is a devastating complication of epilepsy with possible sex\u2010specific risk factors, although the exact relationship between sex and SUDEP remains unclear. To investigate this, we studied\u00a0\n                      <jats:italic>Kcna1<\/jats:italic>\n                      \u00a0knockout (\n                      <jats:italic>Kcna1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      ) mice, which lack voltage\u2010gated Kv1.1 channel subunits and are widely used as a SUDEP model that mirrors key features in humans.\u00a0To assess sex differences, we first performed\u00a0survival analysis, EEG\u2010ECG recordings, seizure threshold testing and retrospective analysis of previous intracardiac pacing data. We then applied a novel modelling approach across organs (organomics) to uncover potential sex\u2010specific differences in brain\u2013heart communication. Our findings revealed female\u00a0\n                      <jats:italic>Kcna1<\/jats:italic>\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \u00a0mice have significantly longer lifespans than males, suggesting lower SUDEP rates. Although no sex differences were found in seizure frequency, duration, burden, susceptibility or interictal heart rate variability, females showed a higher incidence of bradycardia during spontaneous seizures\u00a0than males, as well as\u00a0resistance to inducible ventricular tachyarrhythmias in response to programmed electrical stimulation.\u00a0Two captured SUDEP events, one per sex,\u00a0displayed similar patterns of ictal bradycardia\u00a0in both sexes,\u00a0progressing to postictal cardiorespiratory failure. Going beyond traditional seizure and cardiac metrics, organomics analysis revealed that seizures affect brain\u2013heart communication differently between sexes. Females exhibited more effective resetting of brain\u2013heart interactions postictally than males.\u00a0This finding may contribute to the lower SUDEP risk in females and underscores the complex interplay between sex, cardiac function and brain\u2013heart communication in determining SUDEP susceptibility. Furthermore, seizure\u2010resetting measures could represent a promising class of biomarkers for SUDEP risk stratification.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16496-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Female\n                            <jats:italic>Kcna1<\/jats:italic>\n                            <jats:sup>\u2212\/\u2212<\/jats:sup>\n                            mice live longer than males, suggesting lower sudden unexpected death in epilepsy (SUDEP) rates.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>There are no sex differences in seizure metrics or interictal heart rate variability.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Females show more bradycardia during seizures and are resistant to inducible ventricular tachyarrhythmias.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Seizures affect brain\u2013heart communication differently between the sexes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Seizures in females reset brain\u2013heart interactions more effectively postictally, potentially lowering SUDEP risk.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287582","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T13:05:26Z","timestamp":1736341526000},"page":"6731-6751","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Sex\u2010specific differences in mortality and neurocardiac interactions in the Kv1.1 knockout mouse model of sudden unexpected death in epilepsy (SUDEP)"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4405-3900","authenticated-orcid":false,"given":"Kelsey","family":"Paulhus","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Southern Methodist University  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9365-3929","authenticated-orcid":false,"given":"Praveen","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Southern Methodist University  Dallas TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Kneale","sequence":"additional","affiliation":[{"name":"Departments of Translational Neuroscience and Neurology Barrow Neurological Institute  Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Noah","family":"Hutson","sequence":"additional","affiliation":[{"name":"Departments of Translational Neuroscience and Neurology Barrow Neurological Institute  Phoenix AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4936-3043","authenticated-orcid":false,"given":"Nicole M.","family":"Gautier\u2010Hall","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center  Shreveport LA USA"},{"name":"Department of Pharmacology, Toxicology &amp; Neuroscience Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deng\u2010Shan","family":"Shiau","sequence":"additional","affiliation":[{"name":"EpiFocus LLC  Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Watts","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiology Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle","family":"Trosclair","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemangini A.","family":"Dhaibar","sequence":"additional","affiliation":[{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paari","family":"Dominic","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Section of Cardiology Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas","family":"Iasemidis","sequence":"additional","affiliation":[{"name":"Departments of Translational Neuroscience and Neurology Barrow Neurological Institute  Phoenix AZ USA"},{"name":"EpiFocus LLC  Scottsdale AZ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8702-2349","authenticated-orcid":false,"given":"Edward","family":"Glasscock","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Southern Methodist University  Dallas TX USA"},{"name":"Department of Cellular Biology and Anatomy Louisiana State University Health Sciences Center  Shreveport LA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2012.0158"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/00207454.2023.2279497"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0162-24.2024"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.11.4.585"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.11.018"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.11.037"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4613-0225-4_2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-008-9625-6"},{"issue":"14","key":"e_1_2_5_10_1","article-title":"Gender differences in the incidence of psychiatric co\u2010morbidity in patients with epilepsy (P3.196)","volume":"84","author":"Chan J.","year":"2015","journal-title":"Neurology"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.119.017392"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2017.11.005"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/509282a"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1010481"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(16)30158-2"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2019.04.006"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1201\/9780429246593"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.04.003"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-024-01088-x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2012.235606"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-015-0505-6"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5591-09.2010"},{"key":"e_1_2_5_23_1","first-page":"411","article-title":"Nonlinear dynamics of seizure prediction in a rodent model of epilepsy","volume":"14","author":"Good L. 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