{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:48:22Z","timestamp":1791823702876,"version":"4.3.4"},"reference-count":145,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":287,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["F30NS129239"],"award-info":[{"award-number":["F30NS129239"]}],"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":["NS064033"],"award-info":[{"award-number":["NS064033"]}],"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":["NS089659"],"award-info":[{"award-number":["NS089659"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research","award":["JP22J23281"],"award-info":[{"award-number":["JP22J23281"]}]},{"name":"Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research","award":["JP22KJ0323"],"award-info":[{"award-number":["JP22KJ0323"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Resective surgery for paediatric drug-resistant focal epilepsy often requires extraoperative intracranial electroencephalography recording to accurately localize the epileptogenic zone. This procedure entails multiple neurosurgeries, intracranial electrode implantation and explantation, and days of invasive in-patient evaluation. There is a need for methods to reduce the diagnostic burden and introduce objective epilepsy biomarkers. Our preliminary studies aimed to address these issues by using sevoflurane anaesthesia to rapidly and reversibly activate intraoperative phase\u2013amplitude coupling between delta and high-frequency activities, as well as high-frequency activity-based effective connectivity. Phase\u2013amplitude coupling can serve as a proxy for spike-and-wave discharges, and effective connectivity describes the spatiotemporal dynamics of neural information flow among regions. Notably, sevoflurane activated these interictal electrocorticography biomarkers most robustly in areas whose resection led to seizure freedom. However, they were also increased in normative brain regions that did not require removal for seizure control. Before using these electrocorticography biomarkers prospectively to guide resection, we should understand their endogenous distribution and propagation pathways at different anaesthetic stages. In the current study, we highlighted the normative distribution of delta and high-frequency activity phase\u2013amplitude coupling and effective connectivity under sevoflurane. Normative data were derived from 19 patients, whose ages ranged from 4 to 18 years and included 11 males. All achieved seizure control following focal resection. Electrocorticography was recorded at an isoflurane baseline, during stepwise increases in sevoflurane concentration, and also during extraoperative slow-wave sleep without anaesthesia. Normative electrode sites were then mapped onto a standard cortical surface for anatomical visualization. Dynamic tractography traced white matter pathways that connected sites with significantly augmented biomarkers. Finally, we analysed all sites\u2014regardless of normal or abnormal status\u2014to determine whether sevoflurane-enhanced biomarker values could intraoperatively localize the epileptogenic sites. We found that normative electrocorticography biomarkers increased as a function of sevoflurane concentration, especially in bilateral frontal and parietal lobe regions (Bonferroni-corrected P-values &amp;lt; 0.05). Callosal fibres directly connected homotopic Rolandic regions exhibiting elevated phase\u2013amplitude coupling. The superior longitudinal fasciculus linked frontal and parietal association cortices, showing augmented effective connectivity. Higher biomarker values, particularly at 3\u20134 vol% sevoflurane, characterized epileptogenicity and seizure-onset zone status (Bonferroni-corrected P-values &amp;lt; 0.05). Supplementary analysis showed that epileptogenic sites exhibited less augmentation in delta-based effective connectivity. This study helps clarify the normative distribution of, and plausible propagation pathways supporting, sevoflurane-enhanced electrocorticographic biomarkers. Future work should confirm that sevoflurane-activated electrocorticography biomarkers can predict postoperative seizure outcomes in larger cohorts to establish their clinical utility.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf403","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T13:21:17Z","timestamp":1760448077000},"source":"Crossref","is-referenced-by-count":4,"title":["Normative high-frequency oscillation phase\u2013amplitude coupling and effective connectivity under sevoflurane"],"prefix":"10.1093","volume":"7","author":[{"given":"Ethan","family":"Firestone","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Physiology, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Uda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurosurgery, Osaka Metropolitan University Graduate School of Medicine , Osaka 5458585 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Epileptology, Tohoku University Graduate School of Medicine , Sendai 9808575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Sakakura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurosurgery, University of Tsukuba, Tsukuba , Ibaraki 3058575 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurosurgery, Yokohama City University Graduate School of Medicine , Yokohama, Kanagawa 2360004 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riyo","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurosurgery, National Center Hospital, National Center of Neurology and Psychiatry , Tokyo 1878551 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kitazawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurology and Stroke Medicine, Yokohama City University , Yokohama, Kanagawa 2360004 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong-Won","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurology, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee F","family":"Luat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurology, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Pediatrics, Central Michigan University , Mt. Pleasant, MI 48858 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J","family":"Cools","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Michigan, Detroit Medical Center , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Sood","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Michigan, Detroit Medical Center , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8391-4067","authenticated-orcid":false,"given":"Eishi","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]},{"name":"Department of Neurology, Children\u2019s Hospital of Michigan, Detroit Medical Center, Wayne State University , Detroit, MI 48201 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"2025112901512899700_fcaf403-B1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.seizure.2021.07.010","article-title":"Intellectual outcome from 1 to 5 years after epilepsy surgery in 81 children and adolescents: A longitudinal study","volume":"91","author":"Laguitton","year":"2021","journal-title":"Seizure"},{"key":"2025112901512899700_fcaf403-B2","doi-asserted-by":"crossref","first-page":"107882","DOI":"10.1016\/j.neuropsychologia.2021.107882","article-title":"Social brain networks: Resting-state and task-based connectivity in youth with and without epilepsy","volume":"157","author":"Morningstar","year":"2021","journal-title":"Neuropsychologia"},{"key":"2025112901512899700_fcaf403-B3","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1212\/WNL.0000000000011839","article-title":"Incidence and prevalence of drug-resistant epilepsy: A systematic review and meta-analysis","volume":"96","author":"Sultana","year":"2021","journal-title":"Neurology"},{"key":"2025112901512899700_fcaf403-B4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJM200108023450501","article-title":"A randomized, controlled trial of surgery for temporal-lobe epilepsy","volume":"345","author":"Wiebe","year":"2001","journal-title":"N Engl J Med"},{"key":"2025112901512899700_fcaf403-B5","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJMoa1615335","article-title":"Surgery for drug-resistant epilepsy in children","volume":"377","author":"Dwivedi","year":"2017","journal-title":"N Engl J Med"},{"key":"2025112901512899700_fcaf403-B6","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1212\/WNL.0000000000008966","article-title":"Seizure outcome of pediatric epilepsy surgery: Systematic review and meta-analyses","volume":"94","author":"Widjaja","year":"2020","journal-title":"Neurology"},{"key":"2025112901512899700_fcaf403-B7","first-page":"110","article-title":"Cortical dysplastic lesions in children with intractable epilepsy: Role of complete resection","volume":"100","author":"Hader","year":"2004","journal-title":"J Neurosurg"},{"key":"2025112901512899700_fcaf403-B8","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1684\/j.1950-6945.2006.tb00204.x","article-title":"The epileptogenic zone: General principles","volume":"8","author":"L\u00fcders","year":"2006","journal-title":"Epileptic Disord"},{"key":"2025112901512899700_fcaf403-B9","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1093\/brain\/awp025","article-title":"Role of subdural electrocorticography in prediction of long-term seizure outcome in epilepsy surgery","volume":"132","author":"Asano","year":"2009","journal-title":"Brain"},{"key":"2025112901512899700_fcaf403-B10","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/epi.13515","article-title":"Diagnostic utility of invasive EEG for epilepsy surgery: Indications, modalities, and techniques","volume":"57","author":"Jayakar","year":"2016","journal-title":"Epilepsia"},{"key":"2025112901512899700_fcaf403-B11","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1111\/epi.13298","article-title":"Is SEEG safe? 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