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However, mechanisms of action are not well-defined. The goal of this pilot study was to evaluate the potential of vibrotactile stimulation of the outer ear as a method for activating central brain regions similarly to established vagal nerve stimulation methods. Seven patients with intractable epilepsy undergoing stereotactic electroencephalography (sEEG) monitoring participated in the study. Vibrotactile taVNS was administered across five vibration frequencies (2, 6, 12, 20, and 40 Hz) following a randomized stimulation pattern with 30 trials per frequency. Spectral coherence during stimulation was analyzed across theta (4\u20138 Hz), alpha (8\u201313 Hz), beta (13\u201330 Hz), and broadband gamma (70\u2013170 Hz) frequency bands. At the group level, vibrotactile taVNS significantly increased coherence in theta (effect sizes 6 Hz: r\u2009=\u20090.311; 20 Hz: r\u2009=\u20090.316; 40 Hz: r\u2009=\u20090.264) and alpha bands (effect sizes 20 Hz: r\u2009=\u20090.455; 40 Hz: r\u2009=\u20090.402). Anatomically, multiple limbic brain regions exhibited increased coherence during taVNS compared to baseline. The percentage of total electrode pairs demonstrating increased coherence was also quantified at the individual level. Twenty Hz vibration resulted in the highest percentage of responder pairs across low-frequency coherence measures, with a group-average of 33% of electrode pairs responding, though inter-subject variability was present. Overall, vibrotactile taVNS induced significant low-frequency coherence increases involving several limbic system structures. Further, parametric characterization revealed the presence of inter-subject variability in terms of identifying the vibration frequency with the greatest coherence response. These findings encourage continued research into vibrotactile stimulation as an alternative modality for noninvasive vagus nerve stimulation.<\/jats:p>","DOI":"10.1371\/journal.pone.0310917","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T13:37:13Z","timestamp":1748525833000},"page":"e0310917","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Vibrotactile auricular vagus nerve stimulation alters limbic system connectivity in humans: A pilot study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5492-2241","authenticated-orcid":true,"given":"Kara M.","family":"Donovan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua D.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Yun","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Demarest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8785-9499","authenticated-orcid":true,"given":"Gansheng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon T.","family":"Willie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Brunner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-4201","authenticated-orcid":true,"given":"Jenna L.","family":"Gorlewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C.","family":"Leuthardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"issue":"3","key":"pone.0310917.ref001","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1006\/nlme.1995.1024","article-title":"Post-training unilateral vagal stimulation enhances retention performance in the rat","volume":"63","author":"KB Clark","year":"1995","journal-title":"Neurobiol Learn Mem"},{"issue":"3","key":"pone.0310917.ref002","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1006\/nlme.1998.3863","article-title":"Posttraining electrical stimulation of vagal afferents with concomitant vagal efferent inactivation enhances memory storage processes in the rat","volume":"70","author":"KB Clark","year":"1998","journal-title":"Neurobiol Learn Mem"},{"issue":"1","key":"pone.0310917.ref003","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/4600","article-title":"Enhanced recognition memory following vagus nerve stimulation in human subjects","volume":"2","author":"KB Clark","year":"1999","journal-title":"Nat Neurosci"},{"issue":"5","key":"pone.0310917.ref004","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1016\/j.brs.2022.08.001","article-title":"Vagus nerve stimulation-induced cognitive enhancement: hippocampal neuroplasticity in healthy male rats","volume":"15","author":"LK Olsen","year":"2022","journal-title":"Brain Stimul"},{"issue":"11","key":"pone.0310917.ref005","doi-asserted-by":"crossref","first-page":"972","DOI":"10.4088\/JCP.v63n1103","article-title":"Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer\u2019s disease: a pilot study","volume":"63","author":"MJC Sj\u00f6gren","year":"2002","journal-title":"J Clin Psychiatry"},{"issue":"4","key":"pone.0310917.ref006","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.physbeh.2006.11.009","article-title":"Vagus nerve stimulation potentiates hippocampal LTP in freely-moving rats","volume":"90","author":"Y Zuo","year":"2007","journal-title":"Physiol Behav"},{"key":"pone.0310917.ref007","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.neubiorev.2014.05.005","article-title":"Vagus nerve stimulation\u202625 years later! 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