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This study aimed to investigate whether taVNS modulates indirect markers of phasic and tonic noradrenergic activity. Sixty\u2010six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving taVNS (left cymba concha), once during sham (left earlobe) stimulation. To maximize potential effects, the stimulation was delivered continuously (frequency: 25\u00a0Hz; width: 250\u00a0\u03bcs) at an intensity individually calibrated to the maximal level below pain threshold. The stimulation was administered 10\u00a0min before the oddball task and maintained throughout the session. Event\u2010related pupil dilation (ERPD) to target stimuli and pre\u2010stimulus baseline pupil size were assessed during the oddball task as markers of phasic and tonic noradrenergic activity, respectively. Prior to and at the end of stimulation, tonic pupil size at rest, cortisol, and salivary alpha\u2010amylase were assessed as markers of tonic noradrenergic activity. Finally, we explored the effect of taVNS on cardiac vagal activity, respiratory rate, and salivary flow rate. Results showed a greater ERPD to both target and novelty compared to standard stimuli in the oddball task. In contrast to our hypotheses, taVNS did not impact any of the tested markers. Our findings strongly suggest that continuous stimulation of the cymba concha with the tested stimulation parameters is ineffective to increase noradrenergic activity via a vagal pathway.<\/jats:p>","DOI":"10.1111\/psyp.13984","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T15:35:37Z","timestamp":1641483337000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity"],"prefix":"10.1111","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1383-7638","authenticated-orcid":false,"given":"Martina","family":"D'Agostini","sequence":"first","affiliation":[{"name":"Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-1130","authenticated-orcid":false,"given":"Andreas M.","family":"Burger","sequence":"additional","affiliation":[{"name":"Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Villca Ponce","sequence":"additional","affiliation":[{"name":"Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Claes","sequence":"additional","affiliation":[{"name":"The Mind Body Research Group Department of Neuroscience KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"von Leupoldt","sequence":"additional","affiliation":[{"name":"Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0048-774X","authenticated-orcid":false,"given":"Ilse","family":"Van Diest","sequence":"additional","affiliation":[{"name":"Research Group Health Psychology KU Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2009.06.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.28.061604.135709"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-07-04467.1994"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.06.016"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2134(02)00541-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2007.06.104"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00523"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpsycho.2021.01.003"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118566"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2010.12.019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-7916(94)90063-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/psyp.13571"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsycho.2020.107863"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.05.007"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinph.2021.05.014"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881106075274"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881113480988"},{"key":"e_1_2_7_20_1","first-page":"35","article-title":"Interactions between epinephrine, ascending vagal fibers, and central noradrenergic systems in modulating memory for emotionally arousing events","volume":"6","author":"Chen C. 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