{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:58Z","timestamp":1790618278376,"version":"4.1.0"},"reference-count":107,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371197"],"award-info":[{"award-number":["82371197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7232049"],"award-info":[{"award-number":["7232049"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Disorders of consciousness (DoC) lack an integrated framework to guide neuromodulation. This review updates three hierarchical frameworks\u2014ARAS, mesocircuit, and ICNs\u2014and maps therapeutic targets within each.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We synthesized recent neuroanatomical, optogenetic, neuroimaging, and clinical trial evidence, reevaluating classic frameworks and proposing a hierarchical integration to inform multi\u2010target strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three major updates are identified. In ARAS, glutamatergic neurons in PPN\/LDT and parabrachial nucleus, rather than cholinergic neurons, are the primary arousal drivers; clinical translation relies on peripheral nerve stimulations with variable efficacy. The mesocircuit is expanded from a unidirectional GPi\u2010mediated pathway to a bidirectional GPi\u2013GPe balance modulated by dopamine and adenosine; DBS targeting CM\u2010Pf\/CL shows ~44.7% response rate (38\/85) but lacks RCTs, whereas amantadine remains the sole Level 1 evidence. Within ICNs, the executive control network has the strongest RCT support, though efficacy depends on etiology and consciousness level; salience network stimulation is untested. These frameworks are hierarchically integrated: ARAS sustains wakefulness, mesocircuit enables cortical activation, and ICNs support conscious content.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Future strategies should adopt multi\u2010target, multi\u2010level approaches grounded in individualized network profiling. Priorities include large\u2010scale RCTs for DBS and stratified protocols based on etiology and consciousness level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71037","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:18:36Z","timestamp":1788758316000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neural Circuit Mechanisms of Disorders of Consciousness and Potential Therapeutic Targets of Brain Stimulation"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1539-5539","authenticated-orcid":false,"given":"Yichen","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianqing","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Aviation General Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4702-1231","authenticated-orcid":false,"given":"Sipeng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6715-298X","authenticated-orcid":false,"given":"Qiheng","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0078-5410","authenticated-orcid":false,"given":"Yitong","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-6531","authenticated-orcid":false,"given":"Xiaoke","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2006-9999","authenticated-orcid":false,"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-0312","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University  Beijing China"},{"name":"China National Clinical Research Center for Neurological Diseases  Beijing China"},{"name":"Innovative Center, Beijing Institute of Brain Disorders  Beijing China"},{"name":"Department of Neurosurgery Chinese Institute for Brain Research  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005926"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.14151"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2307\/20735027"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm199405263302107"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1741\u20107015\u20108\u201068"},{"key":"e_1_2_9_7_1","first-page":"381","volume-title":"Progress in Brain Research","author":"Giacino J. T.","year":"2005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.279"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010018\u20100263\u20101"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v8.i12.2520"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010020\u201000428\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013\u20104694(49)90219\u20109"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sc.2008.105"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04284"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22559"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306\u20104522(83)90108\u20102"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.10\u201008\u201002541.1990"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1506854112"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1405\u201016.2016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/ner.13479"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(79)90157\u20104"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20106606\u20106\u201059"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.038"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2025.110815"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.01\u201008\u201000876.1981"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2682"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.1987.tb11220.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.8.2572"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.2341\u201006.2006"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1032\u201019.2019"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0580\u201017.2017"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz031"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sleep.2017.01.002"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4377"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614340113"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1080\/09602010443000588"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1159\/000520435"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/apmr.2001.20831"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1102609"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/09638288.2016.1236414"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.645877"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00420"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-211-27577-0_17"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnrt.2024.100143"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1133893"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134\u2010023\u201007072\u20101"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2023.05.002"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2009.11.002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1417.029"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903150203"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1096\u20109861(19960212)365:3<445::Aid\u2010cne8>3.0.Co;2\u20104"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13010146"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.12822"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14179"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(91)90418\u2010U"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2013.02.009"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5316.1265"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2007.05196.x"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.3109\/02699059009026185"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06041"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.3171\/2015.7.JNS15700"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00020"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12040428"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70274"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3171\/2016.10.JNS161071"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201016470\u20102"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14009"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn\u20102022\u2010001998"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1109\/TNSRE.2024.3368434"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002638\u20104"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/0013\u20104694(69)90060\u20101"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.648"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00412"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2021.9626"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12883\u2010020\u20101607\u20109"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00182"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1177\/02692155221089455"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7195699"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.647517"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000260"},{"key":"e_1_2_9_81_1","first-page":"73","volume-title":"1st Congress of the European Academy of Neurology","author":"Martial C.","year":"2016"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.15974"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci9050103"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00746"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brs.2017.02.001"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1059789"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/5036184"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968310369802"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2015.07.027"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00982"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2971"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2025.1509668"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awz118"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177532"},{"issue":"3","key":"e_1_2_9_95_1","first-page":"169","article-title":"L\u2010DOPA Treatment of Comatose States due to Cerebral Lesions. Preliminary Findings","volume":"18","author":"Di Rocco C.","year":"1974","journal-title":"Journal of Neurosurgical Sciences"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apmr.2018.07.001"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1017\/S003329172510158X"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800005105"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.08.003"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.09.029"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010019\u20100212\u20107"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1440.011"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp313"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(16)00111\u20103"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2022.1001519"},{"key":"e_1_2_9_106_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1213904"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2021.118781"},{"key":"e_1_2_9_108_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci13101362"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71037","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.71037","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.71037","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:13:32Z","timestamp":1790615612000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.71037"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":107,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/cns.71037"],"URL":"https:\/\/doi.org\/10.1002\/cns.71037","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71037"}}