{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:56:15Z","timestamp":1791291375855,"version":"4.3.0"},"reference-count":38,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010418","name":"Institute for Information and Communications Technology Promotion","doi-asserted-by":"publisher","award":["RS\u20102024\u201000357879"],"award-info":[{"award-number":["RS\u20102024\u201000357879"]}],"id":[{"id":"10.13039\/501100010418","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022M3C1A3081294"],"award-info":[{"award-number":["2022M3C1A3081294"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive neuromodulation strategy for drug\u2010resistant epilepsy, but clinical response is heterogeneous. We examined whether electroencephalographic (EEG) and structural magnetic resonance imaging (MRI) phenotypes were associated with active\u2010specific clinical benefit from taVNS.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this single\u2010center, randomized, double\u2010blind, sham\u2010controlled crossover exploratory pilot trial, 14 patients with drug\u2010resistant focal epilepsy received 8\u2009weeks of active taVNS and 8\u2009weeks of sham stimulation, separated by a 4\u2010week washout, in randomized sequence. The primary clinical outcome was seizure reduction ratio (SRR) during active versus sham stimulation. Active\u2010specific clinical benefit was defined as \u0394SRR\u2009=\u2009SRR_active \u2212 SRR_sham. Resting\u2010state EEG was obtained at baseline and at the end of the protocol. Changes in regional relative band power were correlated with \u0394SRR, with a focus on the \u03b2 band based on prior evidence of vagal stimulation\u2010related desynchronization. Baseline structural MRI findings were explored by active\u2010phase responder status.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Active taVNS did not significantly outperform sham stimulation. Mean SRR was 46.26\u2009\u00b1\u200940.96% during active stimulation and 48.62\u2009\u00b1\u200937.27% during sham stimulation, with a mean within\u2010subject difference of \u22122.37\u2009\u00b1\u200916.64% (\n p<\/jats:italic>\n \u2009=\u20090.604). Greater \u03b2\u2010band attenuation was associated with larger active\u2010specific clinical benefit in the occipital (\n \u03c1<\/jats:italic>\n \u2009=\u2009\u22120.723,\n p<\/jats:italic>\n \u2009=\u20090.003,\n q<\/jats:italic>\n \u2009=\u20090.017) and frontal regions (\n \u03c1<\/jats:italic>\n \u2009=\u2009\u22120.657,\n p<\/jats:italic>\n \u2009=\u20090.011,\n q<\/jats:italic>\n \u2009=\u20090.027). Parietal \u03b2\u2010band attenuation showed a nominal association (\n \u03c1<\/jats:italic>\n \u2009=\u2009\u22120.552,\n p<\/jats:italic>\n \u2009=\u20090.041,\n q<\/jats:italic>\n \u2009=\u20090.068). Bilateral structural abnormalities and limbic involvement were more frequent among nonresponders (both\n p<\/jats:italic>\n \u2009=\u20090.021, uncorrected).\n <\/jats:p>\n <\/jats:sec>\n \n Significance<\/jats:title>\n Although primary clinical efficacy was not demonstrated, EEG \u03b2\u2010band modulation and limbic structural network burden may help explain interindividual variability in taVNS benefit. The substantial sham response underscores the need for rigorous sham\u2010controlled taVNS trials.<\/jats:p>\n <\/jats:sec>\n \n Plain Language Summary<\/jats:title>\n About one\u2010third of people with epilepsy keep having seizures despite medication. taVNS is a noninvasive treatment that stimulates a nerve at the outer ear. In this small, carefully blinded trial, active taVNS did not reduce seizures more than an inactive (sham) treatment, and the sham response was large. However, people whose EEG \u03b2 brain waves decreased during the study tended to benefit more, and those with more widespread limbic or structural brain changes tended to benefit less. If confirmed in larger studies, these EEG and MRI markers might help identify who is most likely to respond to taVNS.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/epi4.70354","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:18:02Z","timestamp":1791289082000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcutaneous auricular vagus nerve stimulation in drug\u2010resistant epilepsy: A randomized, sham\u2010controlled crossover trial with exploratory\n EEG<\/scp>\n and\n MRI<\/scp>\n response phenotyping"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6116-9684","authenticated-orcid":false,"given":"Sung Jun","family":"Hong","sequence":"first","affiliation":[{"name":"Biomedical Engineering Research Center Samsung Medical Center Seoul Korea"},{"name":"Smart Healthcare Institute Samsung Medical Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8028-6667","authenticated-orcid":false,"given":"Seok\u2010Yeol","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Neuroscience Center Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7111-4652","authenticated-orcid":false,"given":"Eun Kyung","family":"Bok","sequence":"additional","affiliation":[{"name":"Clinical Research Part for Medical Devices Samsung Medical Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8311-6848","authenticated-orcid":false,"given":"Jung Chul","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical Research Part for Medical Devices Samsung Medical Center Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1232-0135","authenticated-orcid":false,"given":"Yeonggin","family":"Kim","sequence":"additional","affiliation":[{"name":"Smart Healthcare Institute Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology, Neuroscience Center Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4999-995X","authenticated-orcid":false,"given":"Kyousik","family":"Min","sequence":"additional","affiliation":[{"name":"TODOC Co., Ltd. Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5171-1695","authenticated-orcid":false,"given":"Young\u2010Min","family":"Shon","sequence":"additional","affiliation":[{"name":"Smart Healthcare Institute Samsung Medical Center Seoul Korea"},{"name":"Department of Neurology, Neuroscience Center Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul Korea"},{"name":"Department of Medical Device Management and Research SAIHST, Sungkyunkwan University Seoul 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