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Transcutaneous auricular vagus nerve stimulation (taVNS) is a method that provides insights into autonomic nerve modulation. This paper presents a research protocol investigating proof of mechanism for the impact of taVNS on autonomic functions and aims to both deepen theoretical understanding and pave the way for clinically relevant applications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This protocol employs a single-blind, randomized cross-over design involving 10 healthy male participants. Simultaneous assessment of both the afferent and efferent aspects of the vagus nerve will be performed by integrating physiological measures, magnetic resonance imaging, and a questionnaire survey. Electrocardiogram will be measured to assess changes in heart rate, as a primary outcome, and heart rate variability. Active taVNS and sham stimulation will be compared, which ensures precision and blinding. Electrical stimulation will be applied to the left<jats:italic>concha cymba<\/jats:italic>and the left<jats:italic>lobule<\/jats:italic>for the active and sham conditions, respectively. The specific parameters of taVNS involve a pulse width of 250 \u00b5s, a frequency of 25\u00a0Hz, and a current adjusted to the perception threshold (0.1\u00a0mA\u2009\u2264\u20095\u00a0mA), delivered in cycles of 32\u00a0s on and 28\u00a0s off.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This research investigates proof of mechanism for taVNS to elucidate its modulatory effects on the central and peripheral components of the autonomic nervous system. Beyond theoretical insights, the findings will provide a foundation for designing targeted neuromodulation strategies, potentially benefiting diverse patient populations experiencing autonomic dysregulation. By elucidating the neural mechanisms, this study contributes to the evolution of personalized and effective clinical interventions in the field of neuromodulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>JRCT, jRCTs032220332, Registered 13 September 2022;<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/jrct.niph.go.jp\/latest-detail\/jRCTs032220332\">https:\/\/jrct.niph.go.jp\/latest-detail\/jRCTs032220332<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s13030-024-00311-x","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T04:02:03Z","timestamp":1718683323000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Proof of mechanism investigation of Transcutaneous auricular vagus nerve stimulation through simultaneous measurement of autonomic functions: a randomized controlled trial protocol"],"prefix":"10.1186","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0481-914X","authenticated-orcid":false,"given":"Ruri","family":"Katsunuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsunehiko","family":"Takamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiko","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sekiguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"311_CR1","doi-asserted-by":"crossref","unstructured":"Thayer JF, \u00c5hs F, Fredrikson M, Sollers JJ, Wager TD. 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