{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T21:39:13Z","timestamp":1788212353534,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T00:00:00Z","timestamp":1759449600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/T04294X\/1"],"award-info":[{"award-number":["MR\/T04294X\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/V026569\/1"],"award-info":[{"award-number":["MR\/V026569\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012295","name":"NIHR Newcastle Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012295","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Vagus nerve stimulation (VNS) reduces seizure frequency and severity in some, but not all, individuals with epilepsy. The hippocampus has been implicated in VNS response, but is yet to be studied structurally using T1\u2010weighted (T1w) magnetic resonance imaging (MRI). In this study we hypothesized greater hippocampal abnormality in VNS non\u2010responders. Using hippocampal morphometrics, we extracted the volumes of four hippocampal regions from T1w MRI across three groups; VNS responders (), non\u2010responders (), and healthy controls (). We first calculated the multivariate Mahalanobis distance using z\u2010scores from all four hippocampal regions to measure abnormality relative to controls. We then compared traditional univariate measures to the Mahalanobis distance. Response to VNS was defined as having a  seizure reduction 2\u2009years post\u2010implantation. Hippocampal morphometrics were significantly more abnormal in non\u2010responders than responders () using the multivariate Mahalanobis distance. Univariate approaches did not differ significantly between responders and non\u2010responders (). At the group level, non\u2010responders to VNS had greater structural hippocampal abnormality when using the multivariate approach. Conversely, this effect was lost with the univariate analysis. This suggests that abnormality is likely present in different parts of the hippocampus in different individuals. Future studies should incorporate multivariate, and potentially multi\u2010modal, information to better characterize the mechanisms of VNS response.<\/jats:p>","DOI":"10.1111\/epi.18658","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T14:43:56Z","timestamp":1759502636000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hippocampal abnormality and response to vagus nerve stimulation in epilepsy"],"prefix":"10.1111","volume":"66","author":[{"given":"Harry J.","family":"Clifford","sequence":"first","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Fenske","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Horsley","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callum","family":"Simpson","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan","family":"Evans","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-6273","authenticated-orcid":false,"given":"Yujiang","family":"Wang","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"},{"name":"Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"},{"name":"UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"da Silva Costa","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"},{"name":"Northern Centre for Mood Disorders Newcastle University  Newcastle upon Tyne UK"},{"name":"Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2062-8623","authenticated-orcid":false,"given":"Rhys H.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"},{"name":"Neurosciences Royal Victoria Infirmary  Newcastle\u2010upon\u2010Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7658-6384","authenticated-orcid":false,"given":"Sabahat","family":"Iqbal","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology  London UK"},{"name":"Department of Brain Sciences Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron A.","family":"Elliott","sequence":"additional","affiliation":[{"name":"Division of Neurosurgery, Department of Surgery University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Duncan","sequence":"additional","affiliation":[{"name":"UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2144-9838","authenticated-orcid":false,"given":"Peter N.","family":"Taylor","sequence":"additional","affiliation":[{"name":"CNNP Lab, Interdisciplinary Computing and Complex BioSystems Group, School of Computing Newcastle University  Newcastle upon Tyne UK"},{"name":"Faculty of Medical Sciences Newcastle University  Newcastle upon Tyne UK"},{"name":"UCL Queen Square Institute of Neurology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2011.07.002"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2010.10.017"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2020.09.027"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18153"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16661"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2010.03.002"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073813510970"},{"issue":"4","key":"e_1_2_12_9_1","first-page":"60","article-title":"Research article vagus nerve stimulation in adults with drug\u2010resistant epilepsy: efficacy, adverse effects and outcomes","volume":"34","author":"D HO","year":"2017","journal-title":"J Neurol Sci"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.1074997"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2023.109107"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14021"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3171\/2018.6.FOCUS18216"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2020.07.023"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25574"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.15055"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1162\/netn_a_00184"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18192"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.77945"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.04.042"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/kxj037"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.11.024"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104848"},{"key":"e_1_2_12_24_1","doi-asserted-by":"crossref","unstructured":"Horsley J Hall G Simpson C Kozma C Thomas R Wang Y et\u00a0al.Seizure freedom after surgical resection of diffusion\u2010weighted MRI abnormalities. arXiv preprint arXiv:241003548. 2024.","DOI":"10.1111\/epi.18490"},{"key":"e_1_2_12_25_1","article-title":"On the generalized distance in statistics","volume":"80","author":"Mahalanobis PC","year":"1936","journal-title":"Indian J Stat"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.18061"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1177\/2515245919847202"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2017.09.015"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1159\/000504859"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2020.106463"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.839163"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00392"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2020.102205"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00438"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.47.1.260"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1595"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2012.04.128"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2016.10.005"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18658","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.18658","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.18658","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T13:01:57Z","timestamp":1779109317000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.18658"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,3]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/epi.18658"],"URL":"https:\/\/doi.org\/10.1111\/epi.18658","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,3]]},"assertion":[{"value":"2025-05-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}