{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:26:29Z","timestamp":1792589189331,"version":"4.5.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["R01NS112252"],"award-info":[{"award-number":["R01NS112252"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["R01NS134625"],"award-info":[{"award-number":["R01NS134625"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["F31NS131056"],"award-info":[{"award-number":["F31NS131056"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["R01NS108445"],"award-info":[{"award-number":["R01NS108445"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","award":["R01NS110130"],"award-info":[{"award-number":["R01NS110130"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["T32GM007347"],"award-info":[{"award-number":["T32GM007347"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000070","name":"NIBIB","doi-asserted-by":"publisher","award":["T32EB021937"],"award-info":[{"award-number":["T32EB021937"]}],"id":[{"id":"10.13039\/100000070","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>How do brain networks limit seizure activity? In the interictal suppression hypothesis, we recently postulated that high inward connectivity to seizure onset zones (SOZs) from non-involved zones (NIZs) is a sign of broader network suppression. If broad networks appear to be responsible for interictal SOZ suppression, what changes during seizure initiation, spread and termination? For patients with drug-resistant epilepsy, intracranial monitoring offers a view into the electrographic networks that organize around and in response to the SOZ.<\/jats:p>\n                  <jats:p>In this manuscript, we investigate network dynamics in the peri-ictal periods to assess possible mechanisms of seizure suppression and the consequences of this suppression being overwhelmed. Peri-ictal network dynamics were derived from stereo electroencephalography recordings from 75 patients with drug-resistant epilepsy undergoing presurgical evaluation at Vanderbilt University Medical Center. We computed directed connectivity from 5\u2005s windows in the periods between, immediately before, during and after 668 seizures. We aligned connectivity matrices across seizures and patients, then calculated net connectivity changes from the SOZ, propagative zone and NIZ.<\/jats:p>\n                  <jats:p>Across all seizure types, we observed two phases: a rapid increase in directed communication towards the SOZ, followed by a collapse in network connectivity. During the first phase, SOZs could be distinguished from all other regions (one-way ANOVA, P = 8.32 \u00d7 10\u221219\u20132.22 \u00d7 10\u22127). In the second phase and post-ictal period, SOZ inward connectivity decreased yet remained distinct (one-way ANOVA, P = 2.58 \u00d7 10\u221210\u20131.66 \u00d7 10\u22122). NIZs appeared to drive increased SOZ connectivity while intra-NIZ connectivity decreased concordantly. Stratifying by seizure subtype, we found that consciousness-impairing seizures decrease inward connectivity from the NIZ earlier than consciousness-sparing seizures (one-way ANOVA, P &amp;lt; 0.01 after false discovery correction). Tracking network reorganization against a surrogate for seizure involvement highlighted a possible antagonism between seizure propagation and the ability of the NIZ to maintain high connectivity to the SOZ. Finally, we found that inclusion of peri-ictal connectivity improved the accuracy of SOZ classification from previous models to a combined area under the curve of 93%.<\/jats:p>\n                  <jats:p>Overall, NIZs appear actively to increase inhibitory signaling towards the SOZ during seizure onset, possibly to thwart seizure activity. Although inhibition appears insufficient to prevent seizure onset, the inability to restrict seizure propagation might contribute to loss of consciousness during larger seizures. Dynamic connectivity patterns uncovered in this work might: (i) facilitate accurate delineation of surgical targets in focal epilepsy; (ii) reveal why interictal suppression of SOZs might be insufficient to prevent all seizures; and (iii) provide insight into mechanisms of loss of consciousness during certain seizures.<\/jats:p>","DOI":"10.1093\/brain\/awaf215","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T07:55:13Z","timestamp":1749110113000},"page":"4275-4287","source":"Crossref","is-referenced-by-count":12,"title":["Collapse of interictal suppressive networks permits seizure spread"],"prefix":"10.1093","volume":"148","author":[{"given":"Ghassan S","family":"Makhoul","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-0762","authenticated-orcid":false,"given":"Derek J","family":"Doss","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham W","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Neurologic Surgery, Mayo Clinic , Rochester, MN 55902 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Price","family":"Withers","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addison C","family":"Cavender","sequence":"additional","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt Brain Institute, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Neuroscience Program, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Hidalgo Monroy Lerma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anas","family":"Reda","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camden E","family":"Bibro","sequence":"additional","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Liao","sequence":"additional","affiliation":[{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hakmook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Vanderbilt University , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benoit M","family":"Dawant","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Electrical and Computer Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpa B","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Children\u2019s Hospital , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela N","family":"Crudele","sequence":"additional","affiliation":[{"name":"Department of Neurology, Vanderbilt University Medical Center Hospital , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-022X","authenticated-orcid":false,"given":"Christos","family":"Constantinidis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Neuroscience Program, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Ophthalmology and Visual Sciences, Vanderbilt University , Nashville, TN 327235 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-380X","authenticated-orcid":false,"given":"Shawniqua","family":"Williams Roberson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurology, Vanderbilt University Medical Center Hospital , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah K","family":"Bick","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria L","family":"Morgan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Department of Neurology, Vanderbilt University Medical Center Hospital , Nashville, TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario J","family":"Englot","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt University Institute of Imaging Science (VUIIS), Vanderbilt University Medical Center , Nashville, TN 37232 ,","place":["USA"]},{"name":"Vanderbilt Institute for Surgery and Engineering (VISE), Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Vanderbilt Brain Institute, Vanderbilt University , Nashville, TN 37235 ,","place":["USA"]},{"name":"Department of Neurological Surgery, Vanderbilt University Medical Center , Nashville, 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