{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T06:05:00Z","timestamp":1789538700177,"version":"build-2803163510"},"reference-count":47,"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To describe short-term behavioral changes observed during a 2-week transcutaneous auricular vagus nerve stimulation (taVNS) intervention in patients with prolonged disorders of consciousness (pDOC) and to exploratorily compare these changes across baseline diagnostic states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This single-center, single-arm, open-label exploratory study included 50 patients with pDOC (25 with VS\/UWS, 16 with MCS\u2212, and 9 with MCS+) who received taVNS in addition to standard care for 2\u202fweeks. CRS-R assessments were conducted at baseline, week 1, and week 2. The primary outcome was the longitudinal change in the CRS-R total score across the three assessment time points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At week 2, the mean change in CRS-R total score from baseline was 2.40\u202f\u00b1\u202f2.08 points (95% CI, 1.81\u20132.99), with no significant difference among the diagnostic groups. Upward diagnostic transitions occurred in 9\/25 (36.0%) patients with VS\/UWS (VS\u202f\u2192\u202fMCS\u2212,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f7; VS\u202f\u2192\u202fMCS+,\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f2) and Six of 16 (37.5%) patients with MCS\u2212 transitioned to MCS+, but in none of the patients with MCS+.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Short-term CRS-R changes and diagnostic transitions were observed during the 2-week taVNS intervention. Because the study lacked a control group and used unblinded outcome assessment, these changes cannot be attributed specifically to taVNS. The subgroup and early-outcome analyses are exploratory and require confirmation in adequately powered, sham-controlled studies with blinded assessment and longer follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1815827","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:32:56Z","timestamp":1789536776000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Short-term changes in CRS-R scores during transcutaneous auricular vagus nerve stimulation in prolonged disorders of consciousness: a single-arm exploratory study"],"prefix":"10.3389","volume":"17","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":"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":"Guowei","family":"L\u00fc","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":"Fang","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":"Beibei","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Trauma Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Long","family":"Xu","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":"Chen","family":"Xin","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"}]},{"given":"Guohairong","family":"Pan","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"}]},{"given":"Jingwei","family":"Kong","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"}]},{"given":"Xiaoli","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueling","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University","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":"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":"741","DOI":"10.1111\/ene.14151","article-title":"European academy of neurology guideline on the diagnosis of coma and other disorders of consciousness","volume":"27","author":"Kondziella","year":"2020","journal-title":"Eur J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"13471","DOI":"10.1038\/s41598-022-17561-w","article-title":"Predicting outcome of patients with prolonged disorders of consciousness using machine learning models based on medical complexity","volume":"12","author":"Liuzzi","year":"2022","journal-title":"Sci Rep"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1186\/1471-2377-9-35","article-title":"Diagnostic accuracy of the vegetative and minimally conscious state: clinical consensus versus standardized neurobehavioral assessment","volume":"9","author":"Schnakers","year":"2009","journal-title":"BMC Neurol"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1212\/wnl.58.3.349","article-title":"The minimally conscious state: definition and diagnostic criteria","volume":"58","author":"Giacino","year":"2002","journal-title":"Neurology"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s00415-011-6303-7","article-title":"Functional neuroanatomy underlying the clinical subcategorization of minimally conscious state patients","volume":"259","author":"Bruno","year":"2012","journal-title":"J Neurol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1007\/s00415-011-6114-x","article-title":"From unresponsive wakefulness to minimally conscious PLUS and functional locked-in syndromes: recent advances in our understanding of disorders of consciousness","volume":"258","author":"Bruno","year":"2011","journal-title":"J Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e2005","DOI":"10.1212\/WNL.0000000000207820","article-title":"Prevalence of the minimally conscious state among institutionalized patients in the Netherlands: a Nationwide study","volume":"101","author":"Overbeek","year":"2023","journal-title":"Neurology"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1007\/s00415-019-09628-y","article-title":"Minimally conscious state \u2018plus\u2019: diagnostic criteria and relation to functional recovery","volume":"267","author":"Thibaut","year":"2020","journal-title":"J Neurol"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1089\/neu.2019.6429","article-title":"Behavioral recovery and early decision making in patients with prolonged disturbance in consciousness after traumatic brain injury","volume":"37","author":"Giacino","year":"2020","journal-title":"J Neurotrauma"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s13054-025-05429-0","article-title":"Noninvasive neuromodulation for disorders of consciousness: an updated systematic review and meta-analysis","volume":"29","author":"Gao","year":"2025","journal-title":"Crit Care"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/j.brs.2021.01.008","article-title":"Ultrasonic thalamic stimulation in chronic disorders of consciousness","volume":"14","author":"Cain","year":"2021","journal-title":"Brain Stimul"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1177\/02692155221089455","article-title":"Repetitive transcranial magnetic stimulation improves consciousness in some patients with disorders of consciousness","volume":"36","author":"Fan","year":"2022","journal-title":"Clin Rehabil"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1186\/s12967-022-03710-2","article-title":"Sleep patterns correlates with the efficacy of tDCS on post-stroke patients with prolonged disorders of consciousness","volume":"20","author":"Yu","year":"2022","journal-title":"J Transl Med"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"647517","DOI":"10.3389\/fnins.2021.647517","article-title":"The clinical effect of repetitive transcranial magnetic stimulation on the disturbance of consciousness in patients in a vegetative state","volume":"15","author":"Zhang","year":"2021","journal-title":"Front Neurosci"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"7195699","DOI":"10.1155\/2022\/7195699","article-title":"Influence of high-frequency repetitive transcranial magnetic stimulation on neurobehavioral and electrophysiology in patients with disorders of consciousness","volume":"2022","author":"Chen","year":"2022","journal-title":"Neural Plast"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1274432","DOI":"10.3389\/fnins.2023.1274432","article-title":"Current status and prospect of transcutaneous auricular vagus nerve stimulation for disorders of consciousness","volume":"17","author":"Wang","year":"2024","journal-title":"Front Neurosci"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.brs.2016.12.004","article-title":"Transcutaneous auricular vagus nerve stimulation in disorders of consciousness monitored by fMRI: the first case report","volume":"10","author":"Yu","year":"2017","journal-title":"Brain Stimul"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"684791","DOI":"10.3389\/fneur.2021.684791","article-title":"Cerebral hemodynamic correlates of transcutaneous auricular vagal nerve stimulation in consciousness restoration: An open-label pilot study","volume":"12","author":"Yu","year":"2021","journal-title":"Front Neurol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"463","DOI":"10.19852\/j.cnki.jtcm.2022.03.012","article-title":"Transcutaneous auricular vague nerve stimulation improved brain connection activity on patients of disorders of consciousness: a pilot study","volume":"42","author":"Wang","year":"2022","journal-title":"J Tradit Chin Med"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1111\/ner.13148","article-title":"Transcutaneous Vagus nerve stimulation in patients with severe traumatic brain injury: a feasibility trial","volume":"23","author":"Hakon","year":"2020","journal-title":"Neuromodulation"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.brs.2019.12.005","article-title":"Feasibility, safety and efficacy of transauricular vagus nerve stimulation in a cohort of patients with disorders of consciousness","volume":"13","author":"No\u00e9","year":"2020","journal-title":"Brain Stimul"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1080\/02699052.2019.1566832","article-title":"Validation of the Chinese version of the coma recovery scale-revised (CRS-R)","volume":"33","author":"Zhang","year":"2019","journal-title":"Brain Inj"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2020","DOI":"10.1016\/j.apmr.2004.02.033","article-title":"The JFK coma recovery scale-revised: measurement characteristics and diagnostic utility","volume":"85","author":"Giacino","year":"2004","journal-title":"Arch Phys Med Rehabil"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1080\/02699052.2019.1644376","article-title":"Diagnostic accuracy of the CRS-R index in patients with disorders of consciousness","volume":"33","author":"Annen","year":"2019","journal-title":"Brain Inj"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1056\/NEJMoa2400645","article-title":"Cognitive motor dissociation in disorders of consciousness","volume":"391","author":"Bodien","year":"2024","journal-title":"N Engl J Med"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"919","DOI":"10.1002\/ana.26740","article-title":"Feasibility and validity of the coma recovery scale-revised for accelerated standardized testing: a practical assessment tool for detecting consciousness in the intensive care unit","volume":"94","author":"Bodien","year":"2023","journal-title":"Ann Neurol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1093\/jmt\/thaa010","article-title":"Examining the functionality of the MATADOC with the CRS-R: a pilot study","volume":"57","author":"Bodine","year":"2020","journal-title":"J Music Ther"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1323079","DOI":"10.3389\/fnins.2023.1323079","article-title":"The efficacy and safety of transcutaneous auricular vagus nerve stimulation for patients with minimally conscious state: a sham-controlled randomized double-blind clinical trial","volume":"17","author":"Zhou","year":"2023","journal-title":"Front Neurosci"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1002\/ana.24962","article-title":"The repetition of behavioral assessments in diagnosis of disorders of consciousness","volume":"81","author":"Wannez","year":"2017","journal-title":"Ann Neurol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1186\/s12883-015-0455-5","article-title":"Coma recovery scale-r: variability in the disorder of consciousness","volume":"15","author":"Cortese","year":"2015","journal-title":"BMC Neurol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.brs.2014.11.018","article-title":"Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans","volume":"8","author":"Frangos","year":"2015","journal-title":"Brain Stimul"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1111\/ner.12541","article-title":"Optimization of transcutaneous vagus nerve stimulation using functional MRI","volume":"20","author":"Yakunina","year":"2017","journal-title":"Neuromodulation"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"7317","DOI":"10.1038\/s41598-024-84029-4","article-title":"The autonomic response following taVNS predicts changes in level of consciousness in DoC patients","volume":"15","author":"Li","year":"2025","journal-title":"Sci Rep"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/S0079-6123(09)17707-5","article-title":"Natural history of recovery from brain injury after prolonged disorders of consciousness: outcome of patients admitted to inpatient rehabilitation with 1\u20134 year follow-up","volume":"177","author":"Katz","year":"2009","journal-title":"Prog Brain Res"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1212\/WNL.0b013e3181e8e8cc","article-title":"Late recovery after traumatic, anoxic, or hemorrhagic long-lasting vegetative state","volume":"75","author":"Estraneo","year":"2010","journal-title":"Neurology"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e1119","DOI":"10.1136\/bmj.e1119","article-title":"Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors","volume":"344","author":"Hr\u00f3bjartsson","year":"2012","journal-title":"BMJ"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"l6802","DOI":"10.1136\/bmj.l6802","article-title":"Impact of blinding on estimated treatment effects in randomised clinical trials: meta-epidemiological study","volume":"368","author":"Moustgaard","year":"2020","journal-title":"BMJ"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/nrn3475","article-title":"Power failure: why small sample size undermines the reliability of neuroscience","volume":"14","author":"Button","year":"2013","journal-title":"Nat Rev Neurosci"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1136\/bmj.326.7382.219","article-title":"Interaction revisited: the difference between two estimates","volume":"326","author":"Altman","year":"2003","journal-title":"BMJ"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1093\/ije\/dyw320","article-title":"An introduction to multiplicity issues in clinical trials: the what, why, when and how","volume":"46","author":"Li","year":"2017","journal-title":"Int J Epidemiol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/S0895-4356(00)00314-0","article-title":"Adjusting for multiple testing\u2014when and how?","volume":"54","author":"Bender","year":"2001","journal-title":"J Clin Epidemiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1855","DOI":"10.1016\/j.apmr.2012.10.041","article-title":"Functional outcomes in traumatic disorders of consciousness: 5-year outcomes from the National Institute on Disability and Rehabilitation Research traumatic brain injury model systems","volume":"94","author":"Whyte","year":"2013","journal-title":"Arch Phys Med Rehabil"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1089\/neu.2018.5954","article-title":"Disorders of consciousness due to traumatic brain injury: functional status ten years post-injury","volume":"36","author":"Hammond","year":"2019","journal-title":"J Neurotrauma"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"e1488","DOI":"10.1212\/WNL.0000000000010254","article-title":"Multicenter prospective study on predictors of short-term outcome in disorders of consciousness","volume":"95","author":"Estraneo","year":"2020","journal-title":"Neurology"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1080\/02699052.2019.1658220","article-title":"Demographical and clinical indices for long-term evolution of patients in vegetative or in minimally conscious state","volume":"33","author":"Estraneo","year":"2019","journal-title":"Brain Inj"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2497","DOI":"10.1056\/NEJMoa1812757","article-title":"Detection of brain activation in unresponsive patients with acute brain injury","volume":"380","author":"Claassen","year":"2019","journal-title":"N Engl J Med"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2258","DOI":"10.1093\/brain\/awu141","article-title":"Large scale screening of neural signatures of consciousness in patients in a vegetative or minimally conscious state","volume":"137","author":"Sitt","year":"2014","journal-title":"Brain"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1815827\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:32:58Z","timestamp":1789536778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1815827\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":47,"alternative-id":["10.3389\/fneur.2026.1815827"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1815827","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"article-number":"1815827"}}