{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:30:48Z","timestamp":1787927448646,"version":"build-2784847793"},"reference-count":50,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013883","name":"LGS Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013883","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS136297"],"award-info":[{"award-number":["R01NS136297"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UH3NS109557"],"award-info":[{"award-number":["UH3NS109557"]}],"id":[{"id":"10.13039\/100000002","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>Lennox\u2013Gastaut syndrome (LGS) is a severe childhood onset epilepsy marked by drug\u2010resistant seizures and generalized electroencephalographic abnormalities. Because patient\u2010reported seizures are often unreliable, objective biomarkers are needed. This study investigates circadian modulation of aperiodic and oscillatory brain activity as a potential monitoring biomarker of seizure burden in LGS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed baseline intracranial recordings from 19 patients with LGS implanted bilaterally with responsive neurostimulation (RNS) targeting the centromedian\u2013parafascicular thalamic complex (CM\u2010Pf) and premotor frontal cortex in an ongoing clinical trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      : NCT05339126). Aperiodic (nonoscillatory) and periodic (oscillatory) components were extracted from scheduled recordings without epileptiform activity or stimulation. Circadian modulation was defined as the difference between daytime and nighttime measures of these components. Seizure burden was quantified as the percentage of days with at least one reported seizure, pre\u2010 and postimplantation, validated by an objective device\u2010based measure (average daily detections).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher seizure burden was associated with reduced diurnal modulation of both aperiodic and oscillatory activity. This relationship was anatomically specific, appearing as a significant negative correlation only in contacts within an LGS network \u201chotspot\u201d in caudal middle frontal gyrus previously identified in LGS, and a positive correlation in thalamic contacts outside the CM\u2010Pf.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>These results suggest that abnormal circadian rhythmicity may provide a candidate monitoring biomarker of disease severity in LGS that localizes to a previously defined LGS network and may extend beyond the traditional CM\u2010Pf target.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70457","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:57:01Z","timestamp":1787925421000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Circadian modulation of aperiodic background and oscillatory activity as a biomarker of seizure burden in Lennox\u2013Gastaut syndrome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3243-3460","authenticated-orcid":false,"given":"Zo\u00e9","family":"Dary","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Mass General Brigham, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron E. L.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mass General Brigham, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Hook","sequence":"additional","affiliation":[{"name":"Normal Fixel Institute for Neurological Diseases, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremi","family":"Chabros","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mass General Brigham, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8740-3886","authenticated-orcid":false,"given":"Lise","family":"Johnson","sequence":"additional","affiliation":[{"name":"NeuroPace  Mountain View California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha J.","family":"Morrell","sequence":"additional","affiliation":[{"name":"NeuroPace  Mountain View California USA"},{"name":"Department of Neurology and Neurological Science Stanford University  Palo Alto California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher R.","family":"Butson","sequence":"additional","affiliation":[{"name":"Normal Fixel Institute for Neurological Diseases, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Rolston","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mass General Brigham, Harvard Medical School  Boston Massachusetts USA"},{"name":"Center for Brain Circuit Therapeutics, Brigham and Women's Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1002\/acn3.52211","article-title":"Clinical trials for Lennox\u2013Gastaut syndrome: challenges and priorities","volume":"11","author":"Knowles JK","year":"2024","journal-title":"Ann Clin Transl Neurol"},{"key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1055\/s-0037-1601324","article-title":"Lennox\u2010Gastaut syndrome: a state of the art review","volume":"48","author":"Mastrangelo M","year":"2017","journal-title":"Neuropediatrics"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/ana.26280","article-title":"DBS of thalamic centromedian nucleus for 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