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Although belonging to the parasympathetic division of the autonomic nervous system, it is dominated by sensory axons originating in the heart, lungs and airways and the gastrointestinal tract. Electrical stimulation of the cervical vagus nerve via surgically implanted cuff electrodes has been used clinically for the treatment of drug\u2010resistant epilepsy for three decades but has also shown efficacy in the treatment of drug\u2010resistant depression and certain gastrointestinal disorders. Through consideration of the anatomical composition of the vagus nerve, its physiology and its distribution throughout the body, we review the effects of vagus nerve stimulation in the context of drug\u2010resistant epilepsy. This narrative review is divided into two sections: part one surveys the anatomy and physiology of the vagus nerve, and part two describes what we know about how vagus nerve stimulation works.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16599-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp287164","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T04:37:39Z","timestamp":1741754259000},"page":"2201-2217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The physiology, anatomy and stimulation of the vagus nerve in epilepsy"],"prefix":"10.1113","volume":"603","author":[{"given":"Mikaela","family":"Patros","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shobi","family":"Sivathamboo","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology The Alfred Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine, The Royal Melbourne Hospital The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Neurology The Royal Melbourne Hospital  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-1904","authenticated-orcid":false,"given":"Hugh D.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology The Alfred Hospital  Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Neurology The Alfred Hospital  Melbourne Victoria Australia"},{"name":"Department of Medicine, The Royal Melbourne Hospital The University of Melbourne  Parkville Victoria Australia"},{"name":"Department of Neurology The Royal Melbourne Hospital  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3325-6566","authenticated-orcid":false,"given":"Vaughan G.","family":"Macefield","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, School of Translational Medicine Monash University  Melbourne Victoria Australia"},{"name":"Department of Cardiometabolic Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,9]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.04.014"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1933.sp003053"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1990.tb05845.x"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1986.251.4.H764"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1938.1.5.405"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6997(25)06822-X"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.focus.20210023"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00220-X"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1157.1994.tb02482.x"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1566-0702(00)00215-0"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1838(87)90147-0"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-1838(99)00083-1"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12611"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2003.002654"},{"key":"e_1_2_2_16_1","volume-title":"Autonomic Nervous System : Handbook of Clinical Neurology (Series editors: Aminoff, Boller, Swaab)","author":"Buijs R. 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