{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:04:40Z","timestamp":1789538680600,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Hum. Neurosci."],"abstract":"<jats:p>Patients with disorders of consciousness (DOC) have limited options for arousal-promoting interventions. Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive neuromodulation technique, has shown potential to improve conscious behaviors in a subset of patients with DOC. However, substantial interindividual variability in treatment response remains, and reliable objective biomarkers for identifying patients who may benefit are still lacking. This study is designed as a single-center, prospective, exploratory clinical study. A total of 50 patients with DOC will be consecutively recruited from the Neurosurgical Ward for DOC at Beijing Tiantan Hospital, Capital Medical University. All enrolled patients will receive 4\u202fweeks of taVNS treatment in addition to standard rehabilitation. Assessments using the Coma Recovery Scale-Revised (CRS-R), electroencephalography (EEG), and functional near-infrared spectroscopy (fNIRS) will be performed at baseline, week 2, and week 4 of treatment. The primary outcome will be the observed change in the CRS-R total score from baseline to week 4. Secondary outcomes will include changes in CRS-R subscale scores, diagnostic transitions in consciousness state, and prespecified EEG and fNIRS features associated with treatment response. Responders will be defined as patients with an increase of at least 3 points in the CRS-R total score from baseline to week 4. Because this is an uncontrolled single-arm study, the findings will be interpreted as exploratory and hypothesis-generating rather than as evidence of causal efficacy. This study aims to characterize behavioral, electrophysiological, and hemodynamic changes during taVNS plus standard rehabilitation and to identify candidate multimodal biomarkers associated with observed improvement, thereby providing a methodological basis for future randomized controlled trials in this population.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trial registration:<\/jats:bold>\n                    <jats:ext-link>http:\/\/itmctr.ccebtcm.org.cn\/en-US\/ITMCTR2024000734<\/jats:ext-link>\n                    , identifier ITMCTR2024000734\n                  <\/jats:p>","DOI":"10.3389\/fnhum.2026.1868162","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:31:18Z","timestamp":1789536678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal biomarkers of response to transcutaneous auricular vagus nerve stimulation in disorders of consciousness: a study protocol"],"prefix":"10.3389","volume":"20","author":[{"given":"Weihang","family":"Zhai","sequence":"first","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peijing","family":"Rong","sequence":"additional","affiliation":[{"name":"Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"703405","DOI":"10.3389\/fnhum.2021.703405","article-title":"The potential role of fNIRS in evaluating levels of consciousness","volume":"15","author":"Abdalmalak","year":"2021","journal-title":"Front. 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