{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T17:12:54Z","timestamp":1793293974901,"version":"4.5.0"},"reference-count":57,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T00:00:00Z","timestamp":1762646400000},"content-version":"unspecified","delay-in-days":8,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Project Number 493623784"],"award-info":[{"award-number":["Project Number 493623784"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gerhard Domagk Nachwuchsf\u00f6rderprogramm"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,18]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Research in people with relapsing remitting multiple sclerosis (PwRRMS) is increasingly focusing on non-motor symptoms like cognitive impairment, fatigue and depression. Due to the high negative impact on quality of life and high socioeconomic costs based on these symptoms, more specific research to improve non-motor symptoms is needed. Transcutaneous auricular vagus nerve stimulation (taVNS) has been found to be a cognitive enhancer in preclinical research and was successfully used for the treatment of psychiatric and neurological disorders to combat dysfunctional cognitive and affective processes. However, the capacity of taVNS to improve cognitive and other non-motor symptoms in PwRRMS has not been tested yet. The aim of this study is to evaluate the therapeutic potential of taVNS on cognitive processing speed. Based on ample evidence demonstrating that taVNS promotes adaptive cognitive and affective processes, we hypothesised that taVNS would alleviate cognitive processing speed in PwRRMS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This study protocol describes the prospective, single-centre, SHAM-controlled, single-blinded trial with a planned sample size of 60 participants (30 PwRRMS, with a diagnosis of multiple sclerosis according to McDonald criteria and 30 healthy controls; age: 18\u201350 years). The Symbol Digit Modalities Test (SDMT) will be used to determine cognitive processing speed, Beck Depression Inventory-II to determine depression and Fatigue Scale for Motor and Cognitive Functions to determine fatigue. The severity of multiple sclerosis will be assessed using the Expanded Disability Status Scale. After baseline assessment, a taVNS protocol (duration: 30\u2009min, tolerance threshold, pulse width: 250 \u03bcs, stimulation frequency: 25\u2009Hz, 30\u2009s on\/30\u2009s off) will be applied, followed by post-intervention assessment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>\n                      The study was reviewed and approved by the local ethics committee of the University Medical Centre Greifswald (study reference number: BB137\/24). Clinical trial registration:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"www.drks.de\">www.drks.de<\/jats:ext-link>\n                      , number: DRKS00034912. Study results will be disseminated through academic conferences as well as peer-reviewed publications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>DRKS00034912.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-103998","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T05:45:43Z","timestamp":1762753543000},"page":"e103998","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Effect of non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) on non-motor symptoms in multiple sclerosis: study protocol for a randomised, controlled trial"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6844-1968","authenticated-orcid":false,"given":"Thorsten","family":"Herr","sequence":"first","affiliation":[{"name":"Department of Neurology, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Gamain","sequence":"additional","affiliation":[{"name":"Department for Radiology, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Strauss","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Szeska","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology and Affective Science, University of Potsdam, Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1475-5872","authenticated-orcid":false,"given":"Agnes","family":"Fl\u00f6el","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medicine Greifswald, Greifswald, Germany"},{"name":"Department of Neurology, German Centre for Neurodegenerative Diseases, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris-Katharina","family":"Penner","sequence":"additional","affiliation":[{"name":"Inselspital University Hospital Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3968-9656","authenticated-orcid":false,"given":"Mathias","family":"Weymar","sequence":"additional","affiliation":[{"name":"Department of Biological Psychology and Affective Science, University of Potsdam, Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Grothe","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,11,9]]},"reference":[{"key":"2025120413263201000_15.11.e103998.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30481-1"},{"key":"2025120413263201000_15.11.e103998.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30277-5"},{"key":"2025120413263201000_15.11.e103998.3","doi-asserted-by":"crossref","first-page":"877","DOI":"10.30773\/pi.2019.0106","article-title":"Neuropsychiatric Symptoms of Multiple Sclerosis: State of the Art","volume":"16","author":"Silveira","year":"2019","journal-title":"Psychiatry Investig"},{"key":"2025120413263201000_15.11.e103998.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2023.05.048"},{"key":"2025120413263201000_15.11.e103998.5","doi-asserted-by":"crossref","unstructured":"Giraudier M , Ventura-Bort C , Szeska C , et al . 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