{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:54:49Z","timestamp":1783018489641,"version":"3.54.6"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":174,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003009","name":"Science and Technology Innovation 2030-Major Project on Brain Science and Brain-like Research","doi-asserted-by":"publisher","award":["2022ZD0208000"],"award-info":[{"award-number":["2022ZD0208000"]}],"id":[{"id":"10.13039\/501100003009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017591","name":"Key Industrial Innovation Chain","doi-asserted-by":"publisher","award":["2024SF-ZDCYL-02-06"],"award-info":[{"award-number":["2024SF-ZDCYL-02-06"]}],"id":[{"id":"10.13039\/501100017591","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["92259304"],"award-info":[{"award-number":["92259304"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022600","name":"Medical Personnel Boosting Program of Xijing Hospital","doi-asserted-by":"publisher","award":["XJZT24JC15"],"award-info":[{"award-number":["XJZT24JC15"]}],"id":[{"id":"10.13039\/501100022600","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical Personnel Skill Enhancement Program of Xijing Hospital","award":["2024XJSM04"],"award-info":[{"award-number":["2024XJSM04"]}]},{"name":"Medical Personnel Skill Enhancement Program of Xijing Hospital","award":["2024XJSY35"],"award-info":[{"award-number":["2024XJSY35"]}]},{"DOI":"10.13039\/501100017596","name":"Basic Research Program for Natural Science of Shaanxi Province","doi-asserted-by":"publisher","award":["2025JC-YBMS-929"],"award-info":[{"award-number":["2025JC-YBMS-929"]}],"id":[{"id":"10.13039\/501100017596","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The glymphatic system is essential for removing metabolic waste from the brain and facilitating the distribution of nutrients, but its status in patients with chronic disorders of consciousness (DoC) remains poorly understood. This study evaluated glymphatic function in chronic DoC and investigated its association with regional cerebral glucose metabolism. Forty-one patients with chronic DoC and 26 healthy controls (HCs) were retrospectively included. All participants underwent 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography\/magnetic resonance imaging (PET\/MRI). Glymphatic function was quantified using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Standardized uptake value ratios (SUVRs) of key hubs within the \u2018mesocircuit model\u2019 were calculated using the cerebellum as reference. The characteristic glucose metabolic pattern (GMP) of chronic DoC was identified, and its expression scores were computed. Associations between the glymphatic function and cerebral glucose metabolism, behavioural score and serological markers were evaluated. Patients with chronic DoC showed significantly lower DTI-ALPS indices than HCs (P &amp;lt; 0.001). Within the patient group, moderate to strong correlations were observed between the DTI-ALPS index and the SUVRs of mesocircuit-associated regions, including the frontal cortex (r = 0.335, P = 0.002), parietal cortex (r = 0.383, P &amp;lt; 0.001), thalamus (r = 0.528, P &amp;lt; 0.001), brainstem (r = 0.665, P &amp;lt; 0.001), striatum (r = 0.537, P &amp;lt; 0.001) and globus pallidus (r = 0.372, P = 0.001), but not with the GMP score, behavioural score, or serological markers (all P &amp;gt; 0.05). Multivariate analysis further revealed that older age (\u03b2 = \u22120.312, P &amp;lt; 0.001) and lower SUVRs in the parietal cortex (\u03b2 = 0.196, P = 0.030) and brainstem (\u03b2 = 0.482, P &amp;lt; 0.001) independently predicted reduced DTI-ALPS indices. This study provides in vivo evidence that glymphatic dysfunction is significantly associated with regional cerebral hypometabolism in chronic DoC, particularly in the parietal cortex and brainstem, which may serve as physiological drivers of CSF circulation.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag235","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:38:43Z","timestamp":1782214723000},"source":"Crossref","is-referenced-by-count":0,"title":["Association between glymphatic dysfunction and glucose hypometabolism in chronic disorders of consciousness: a multimodal PET\/MRI study"],"prefix":"10.1093","volume":"8","author":[{"given":"Yirong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Communication & Information Engineering, Shanghai University , Shanghai 200444 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoqi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich , Munich 81675 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4948-3683","authenticated-orcid":false,"given":"Jiehui","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Shanghai University , Shanghai 200444 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University , Xi\u2019an, Shaanxi 710032 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"issue":"6","key":"2026070213420458300_fcag235-B1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S1474-4422(19)30031-6","article-title":"Therapeutic interventions in patients with prolonged disorders of consciousness","volume":"18","author":"Thibaut","year":"2019","journal-title":"Lancet Neurol"},{"issue":"2","key":"2026070213420458300_fcag235-B2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/nrneurol.2013.279","article-title":"Disorders of consciousness after acquired brain injury: The state of the science","volume":"10","author":"Giacino","year":"2014","journal-title":"Nat Rev Neurol"},{"issue":"6","key":"2026070213420458300_fcag235-B3","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1093\/brain\/awab063","article-title":"Prolonged disorders of consciousness: A critical evaluation of the new UK guidelines","volume":"144","author":"Scolding","year":"2021","journal-title":"Brain J Neurol"},{"issue":"7","key":"2026070213420458300_fcag235-B4","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/S1474-4422(20)30117-4","article-title":"Brain injury after cardiac arrest: From prognostication of comatose patients to rehabilitation","volume":"19","author":"Cronberg","year":"2020","journal-title":"Lancet Neurol"},{"issue":"9","key":"2026070213420458300_fcag235-B5","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S1474-4422(04)00852-X","article-title":"Brain function in coma, vegetative state, and related disorders","volume":"3","author":"Laureys","year":"2004","journal-title":"Lancet Neurol"},{"issue":"17","key":"2026070213420458300_fcag235-B6","doi-asserted-by":"crossref","first-page":"6473","DOI":"10.1073\/pnas.1320969111","article-title":"Regional cerebral metabolic patterns demonstrate the role of anterior forebrain mesocircuit dysfunction in the severely injured brain","volume":"111","author":"Fridman","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2026070213420458300_fcag235-B7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/jcbfm.2014.169","article-title":"Quantitative rates of brain glucose metabolism distinguish minimally conscious from vegetative state patients","volume":"35","author":"Stender","year":"2015","journal-title":"J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab"},{"issue":"11","key":"2026070213420458300_fcag235-B8","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1016\/j.cub.2016.04.024","article-title":"The minimal energetic requirement of sustained awareness after brain injury","volume":"26","author":"Stender","year":"2016","journal-title":"Curr Biol"},{"issue":"2","key":"2026070213420458300_fcag235-B9","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1152\/physrev.00031.2020","article-title":"Fluid transport in the brain","volume":"102","author":"Rasmussen","year":"2022","journal-title":"Physiol Rev"},{"issue":"10","key":"2026070213420458300_fcag235-B10","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1038\/s41573-022-00500-9","article-title":"The glymphatic system: Implications for drugs for central nervous system diseases","volume":"21","author":"Lohela","year":"2022","journal-title":"Nat Rev Drug Discov"},{"key":"2026070213420458300_fcag235-B11","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1016\/j.neuron.2025.04.027","article-title":"Selective removal of astrocytic PERK protects against glymphatic impairment and decreases toxic aggregation of \u03b2-amyloid and tau","volume":"113","author":"Chen","year":"2025","journal-title":"Neuron"},{"issue":"1","key":"2026070213420458300_fcag235-B12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41531-024-00643-z","article-title":"Phosphorylation of AQP4 by LRRK2 R1441G impairs glymphatic clearance of IFN\u03b3 and aggravates dopaminergic neurodegeneration","volume":"10","author":"Huang","year":"2024","journal-title":"NPJ Park Dis"},{"issue":"49","key":"2026070213420458300_fcag235-B13","doi-asserted-by":"crossref","first-page":"16180","DOI":"10.1523\/JNEUROSCI.3020-14.2014","article-title":"Impairment of glymphatic pathway function promotes tau pathology after traumatic brain injury","volume":"34","author":"Iliff","year":"2014","journal-title":"J Neurosci Off J Soc Neurosci"},{"issue":"7","key":"2026070213420458300_fcag235-B14","doi-asserted-by":"crossref","first-page":"e70526","DOI":"10.1111\/cns.70526","article-title":"Glymphatic function as a prognostic biomarker in prolonged disorders of consciousness","volume":"31","author":"Wu","year":"2025","journal-title":"CNS Neurosci Ther"},{"issue":"8002","key":"2026070213420458300_fcag235-B15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41586-024-07108-6","article-title":"Neuronal dynamics direct cerebrospinal fluid perfusion and brain clearance","volume":"627","author":"Jiang-Xie","year":"2024","journal-title":"Nature"},{"issue":"4","key":"2026070213420458300_fcag235-B16","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1007\/s11604-017-0617-z","article-title":"Evaluation of glymphatic system activity with the diffusion MR technique: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) in Alzheimer\u2019s disease cases","volume":"35","author":"Taoka","year":"2017","journal-title":"Jpn J Radiol"},{"issue":"5","key":"2026070213420458300_fcag235-B17","doi-asserted-by":"crossref","first-page":"3251","DOI":"10.1002\/alz.13789","article-title":"Glymphatic system dysfunction predicts amyloid deposition, neurodegeneration, and clinical progression in Alzheimer\u2019s disease","volume":"20","author":"Huang","year":"2024","journal-title":"Alzheimers Dement J Alzheimers Assoc"},{"issue":"3","key":"2026070213420458300_fcag235-B18","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ana.26710","article-title":"Regional glymphatic abnormality in behavioral variant frontotemporal dementia","volume":"94","author":"Jiang","year":"2023","journal-title":"Ann Neurol"},{"issue":"1","key":"2026070213420458300_fcag235-B19","doi-asserted-by":"crossref","first-page":"e210055","DOI":"10.1212\/WNL.0000000000210055","article-title":"Association of glymphatic function with clinical characteristics in patients with clinical and asymptomatic Creutzfeldt-Jakob disease","volume":"104","author":"Chen","year":"2025","journal-title":"Neurology"},{"issue":"4","key":"2026070213420458300_fcag235-B20","first-page":"1885","article-title":"Cross-vendor test-retest validation of diffusion tensor image analysis along the perivascular space (DTI-ALPS) for evaluating glymphatic system function","volume":"15","author":"Liu","year":"2024","journal-title":"Aging Dis"},{"issue":"6","key":"2026070213420458300_fcag235-B21","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1038\/s41593-023-01327-2","article-title":"Glymphatic influx and clearance are accelerated by neurovascular coupling","volume":"26","author":"Holstein-R\u00f8nsbo","year":"2023","journal-title":"Nat Neurosci"},{"issue":"3","key":"2026070213420458300_fcag235-B22","doi-asserted-by":"crossref","first-page":"e3002035","DOI":"10.1371\/journal.pbio.3002035","article-title":"Neural activity induced by sensory stimulation can drive large-scale cerebrospinal fluid flow during wakefulness in humans","volume":"21","author":"Williams","year":"2023","journal-title":"PLoS Biol"},{"issue":"7","key":"2026070213420458300_fcag235-B23","doi-asserted-by":"crossref","first-page":"e0298110","DOI":"10.1371\/journal.pone.0298110","article-title":"Lateral frontoparietal effective connectivity differentiates and predicts state of consciousness in a cohort of patients with traumatic disorders of consciousness","volume":"19","author":"Ihalainen","year":"2024","journal-title":"PLoS One"},{"key":"2026070213420458300_fcag235-B24","doi-asserted-by":"crossref","first-page":"120988","DOI":"10.1016\/j.neuroimage.2024.120988","article-title":"Cardiac and respiratory activities induce temporal changes in cerebral blood volume, balanced by a mirror CSF volume displacement in the spinal canal","volume":"305","author":"Liu","year":"2025","journal-title":"NeuroImage"},{"issue":"5","key":"2026070213420458300_fcag235-B25","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.biopsych.2021.05.025","article-title":"Traumatic brain injury and risk of neurodegenerative disorder","volume":"91","author":"Brett","year":"2022","journal-title":"Biol Psychiatry"},{"issue":"6","key":"2026070213420458300_fcag235-B26","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1172\/JCI135530","article-title":"Immune responses to stroke: Mechanisms, modulation, and therapeutic potential","volume":"130","author":"Iadecola","year":"2020","journal-title":"J Clin Invest"},{"issue":"1","key":"2026070213420458300_fcag235-B27","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s13054-017-1670-9","article-title":"Clinical pathophysiology of hypoxic ischemic brain injury after cardiac arrest: A \u201ctwo-hit\u201d model","volume":"21","author":"Sekhon","year":"2017","journal-title":"Crit Care Lond Engl"},{"issue":"1","key":"2026070213420458300_fcag235-B28","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1001\/jamaneurol.2016.4370","article-title":"Association of perivascular localization of aquaporin-4 with cognition and Alzheimer disease in aging brains","volume":"74","author":"Zeppenfeld","year":"2017","journal-title":"JAMA Neurol"},{"issue":"8","key":"2026070213420458300_fcag235-B29","doi-asserted-by":"crossref","first-page":"e829","DOI":"10.1212\/WNL.0000000000013215","article-title":"Association of sleep, neuropsychological performance, and gray matter volume with glymphatic function in community-dwelling older adults","volume":"98","author":"Siow","year":"2022","journal-title":"Neurology"},{"issue":"1","key":"2026070213420458300_fcag235-B30","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1038\/s41467-023-36643-5","article-title":"Sleep cycle-dependent vascular dynamics in male mice and the predicted effects on perivascular cerebrospinal fluid flow and solute transport","volume":"14","author":"Bojarskaite","year":"2023","journal-title":"Nat Commun"},{"issue":"1","key":"2026070213420458300_fcag235-B31","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1186\/s12916-020-01812-6","article-title":"Sleep in disorders of consciousness: Behavioral and polysomnographic recording","volume":"18","author":"Mertel","year":"2020","journal-title":"BMC Med"},{"issue":"11","key":"2026070213420458300_fcag235-B32","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1002\/hbm.26386","article-title":"Whole-brain analyses indicate the impairment of posterior integration and thalamo-frontotemporal broadcasting in disorders of consciousness","volume":"44","author":"Panda","year":"2023","journal-title":"Hum Brain Mapp"},{"issue":"2","key":"2026070213420458300_fcag235-B33","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1523\/JNEUROSCI.3742-14.2015","article-title":"Biomarkers of traumatic injury are transported from brain to blood via the glymphatic system","volume":"35","author":"Plog","year":"2015","journal-title":"J Neurosci Off J Soc Neurosci"},{"key":"2026070213420458300_fcag235-B34","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1038\/srep02582","article-title":"Paravascular microcirculation facilitates rapid lipid transport and astrocyte signaling in the brain","volume":"3","author":"Rangroo Thrane","year":"2013","journal-title":"Sci Rep"},{"key":"2026070213420458300_fcag235-B35","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.1038\/ncomms7807","article-title":"Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism","volume":"6","author":"Lundgaard","year":"2015","journal-title":"Nat Commun"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcag235\/68603858\/fcag235.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/4\/fcag235\/68603858\/fcag235.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/8\/4\/fcag235\/68603858\/fcag235.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T17:46:59Z","timestamp":1783014419000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcag235\/8715432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7,1]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcag235","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026]]},"published":{"date-parts":[[2026]]},"article-number":"fcag235"}}