{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T06:01:31Z","timestamp":1785132091502,"version":"3.55.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82230063"],"award-info":[{"award-number":["82230063"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-term exposure to a high-altitude (HA) hypoxic environment induces cognitive impairments, but the underlying mechanisms remain unclear. Notably, the specific topological features of brain networks in this context have not been thoroughly explored. This study investigated graph-based topological characteristics of brain networks from static and dynamic perspectives, and examined how these alterations contribute to the chronic HA-induced cognitive changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This longitudinal panel study enrolled 49 college freshmen who relocated from low altitude to a HA region in Tibet. Comprehensive cognitive assessments and brain magnetic resonance imaging (MRI) were performed at baseline, 2 years, and 4 years. Resting-state functional MRI data were used to characterize the topological organization of functional brain networks, encompassing both nodal and global network properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Behavioral assessments showed persistent impairments in cognitive functions following prolonged HA exposure. Neuroimaging analyses consistently identified the left superior parietal gyrus, left inferior parietal lobule, and right Heschl\u2019s gyrus as key nodes for both static and dynamic nodal properties. After 4 years of HA exposure, all dynamic global network metrics were elevated relative to baseline values, and these alterations were associated significantly with cognitive changes. Specifically, increased variances of characteristic path length (Lp) and global efficiency (Eglob) correlated with working memory decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings demonstrate that variances in Lp and Eglob contribute significantly to chronic hypoxia-induced cognitive impairment. Collectively, these results provide novel evidence that dynamic functional instability, as reflected by altered fluctuations in Lp and Eglob, plays a pivotal role in driving hypoxia-related cognitive decline.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1773258","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:39:50Z","timestamp":1785130790000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Alterations in static and dynamic topological properties of brain functional network after chronic high altitude exposure: a panel study"],"prefix":"10.3389","volume":"18","author":[{"given":"Siyao","family":"Zeng","sequence":"first","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sijia","family":"Guo","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ou","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Yang","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong","family":"Xue","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqin","family":"Liu","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"The General Hospital of PLA Xizang Military Area Command","place":["Lhasa, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Luo","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Chen","sequence":"additional","affiliation":[{"name":"The Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environments, Shaanxi Provincial Key Laboratory of Environmental Health Hazard Assessment and Protection, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University","place":["Xi\u2019an, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10179","DOI":"10.3390\/ijms241210179","article-title":"The brain at high altitude: From molecular signaling to cognitive performance.","volume":"24","author":"Aboouf","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1093\/cercor\/bhs352","article-title":"Tracking whole-brain connectivity dynamics in the resting state.","volume":"24","author":"Allen","year":"2014","journal-title":"Cereb. Cortex"},{"key":"B3","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1177\/1073858406293182","article-title":"Small-world brain networks","volume":"12","author":"Bassett","year":"2006","journal-title":"Neuroscientist."},{"key":"B4","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/nrn2575","article-title":"Complex brain networks: Graph theoretical analysis of structural and functional systems.","volume":"10","author":"Bullmore","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"149169","DOI":"10.1016\/j.brainres.2024.149169","article-title":"The impact of insomnia on brain networks topology in depressed patients: A resting-state fMRI study.","volume":"1844","author":"Chen","year":"2024","journal-title":"Brain Res."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1002\/hbm.24696","article-title":"Combined fractional anisotropy and subcortical volumetric abnormalities in healthy immigrants to high altitude: A longitudinal study.","volume":"40","author":"Chen","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"B7","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s11682-019-00241-1","article-title":"Altered resting-state networks may explain the executive impairment in young health immigrants into high-altitude area.","volume":"15","author":"Chen","year":"2021","journal-title":"Brain Imaging Behav."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3865","DOI":"10.1002\/hbm.23635","article-title":"Cognitive and neuroimaging changes in healthy immigrants upon relocation to a high altitude: A panel study.","volume":"38","author":"Chen","year":"2017","journal-title":"Hum. Brain Mapp."},{"key":"B9","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/ner.12346","article-title":"Spinal Cord Stimulation (SCS) and Functional Magnetic Resonance Imaging (fMRI): Modulation of cortical connectivity with therapeutic SCS.","volume":"19","author":"Deogaonkar","year":"2016","journal-title":"Neuromodulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1038\/s41537-022-00288-y","article-title":"Network hub centrality and working memory performance in schizophrenia.","volume":"8","author":"Eryilmaz","year":"2022","journal-title":"Schizophrenia"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1679858","DOI":"10.3389\/fnins.2025.1679858","article-title":"Unraveling the complexity of cognitive impairment following high-altitude exposure: From preclinical animal models to human organoids.","volume":"19","author":"Gong","year":"2025","journal-title":"Front. Neurosci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1097\/01.wno.0000205978.86281.3e","article-title":"Diffusion tensor magnetic resonance imaging.","volume":"26","author":"Gulani","year":"2006","journal-title":"J. Neuroophthalmol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1002\/hbm.25786","article-title":"Intersubject correlation analysis reveals the plasticity of cerebral functional connectivity in the long-term use of social media.","volume":"43","author":"Hu","year":"2022","journal-title":"Hum. Brain Mapp."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1201","DOI":"10.1007\/s00234-022-02895-z","article-title":"Abnormal static and dynamic functional connectivity of networks related to cognition in patients with subcortical ischemic vascular disease.","volume":"64","author":"Huang","year":"2022","journal-title":"Neuroradiology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2955","DOI":"10.1093\/brain\/awx233","article-title":"Abnormal intrinsic brain functional network dynamics in Parkinson\u2019s disease.","volume":"140","author":"Kim","year":"2017","journal-title":"Brain"},{"key":"B16","doi-asserted-by":"publisher","first-page":"12539","DOI":"10.1038\/s41598-026-42645-2","article-title":"Chronic high-altitude exposure and cognitive health in Chinese college students: a 4-year longitudinal neuroimaging study","volume":"16","author":"Li","year":"2026","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1186\/s13098-024-01484-9","article-title":"Network efficiency of functional brain connectomes altered in type 2 diabetes patients with and without mild cognitive impairment.","volume":"16","author":"Li","year":"2024","journal-title":"Diabetol. Metab. Syndr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e14786","DOI":"10.1111\/cns.14786","article-title":"Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea.","volume":"30","author":"Li","year":"2024","journal-title":"CNS Neurosci. Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"808","DOI":"10.3390\/brainsci12060808","article-title":"Effects of long-term exposure to high altitude hypoxia on cognitive function and its mechanism: A narrative review.","volume":"12","author":"Li","year":"2022","journal-title":"Brain Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1089\/brain.2014.0253","article-title":"DynamicBC: A MATLAB toolbox for dynamic brain connectome analysis.","volume":"4","author":"Liao","year":"2014","journal-title":"Brain Connect."},{"key":"B21","doi-asserted-by":"publisher","first-page":"119265","DOI":"10.1016\/j.neuroimage.2022.119265","article-title":"Prefrontal control of social influence in risk decision making.","volume":"257","author":"Lin","year":"2022","journal-title":"Neuroimage"},{"key":"B22","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1089\/ham.2022.0136","article-title":"The effect of high-altitude hypoxia on neuropsychiatric functions.","volume":"25","author":"Liu","year":"2024","journal-title":"High Alt. Med. Biol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.3174\/ajnr.A5527","article-title":"Resting-state functional MRI: Everything that nonexperts have always wanted to know.","volume":"39","author":"Lv","year":"2018","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1111\/cns.12397","article-title":"Epicentral disruption of structural connectivity in Alzheimer\u2019s disease.","volume":"21","author":"Mallio","year":"2015","journal-title":"CNS Neurosci. Ther."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e63591","DOI":"10.7554\/eLife.63591","article-title":"Functional specialization within the inferior parietal lobes across cognitive domains.","volume":"10","author":"Numssen","year":"2021","journal-title":"Elife"},{"key":"B26","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1016\/j.neuron.2013.07.035","article-title":"Evidence for hubs in human functional brain networks.","volume":"79","author":"Power","year":"2013","journal-title":"Neuron"},{"key":"B27","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1089\/ham.2024.0063","article-title":"Temporal effects of hypoxia exposure at high altitudes on compensatory brain function: Evidence from functional connectivity of resting-state EEG brain networks.","volume":"26","author":"Ren","year":"2025","journal-title":"High Alt. Med. Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/hbm.20517","article-title":"Small-world properties of nonlinear brain activity in schizophrenia.","volume":"30","author":"Rubinov","year":"2009","journal-title":"Hum. Brain Mapp."},{"key":"B29","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1023\/a:1026080320034","article-title":"High altitude hypoxia: An intricate interplay of oxygen responsive macroevents and micromolecules.","volume":"253","author":"Sarkar","year":"2003","journal-title":"Mol. Cell. Biochem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1093\/cercor\/bhx179","article-title":"Local-global parcellation of the human cerebral cortex from intrinsic functional connectivity MRI.","volume":"28","author":"Schaefer","year":"2018","journal-title":"Cereb. Cortex"},{"key":"B31","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1148\/radiol.2016160907","article-title":"Anatomic insights into disrupted small-world networks in pediatric posttraumatic stress disorder.","volume":"282","author":"Suo","year":"2017","journal-title":"Radiology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"149113","DOI":"10.1016\/j.brainres.2024.149113","article-title":"Evidence that robot-assisted gait training modulates neuroplasticity after stroke: An fMRI pilot study based on graph theory analysis","volume":"1842","author":"Tang","year":"2024","journal-title":"Brain Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1006\/nimg.2001.0978","article-title":"Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.","volume":"15","author":"Tzourio-Mazoyer","year":"2002","journal-title":"Neuroimage"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/j.biopsych.2015.04.016","article-title":"Dynamic network communication as a unifying neural basis for cognition, development, aging, and disease.","volume":"77","author":"Voytek","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"B35","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3389\/fnhum.2015.00386","article-title":"GRETNA: A graph theoretical network analysis toolbox for imaging connectomics.","volume":"9","author":"Wang","year":"2015","journal-title":"Front. Hum. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e37890","DOI":"10.1016\/j.heliyon.2024.e37890","article-title":"Abnormal intrinsic brain functional network dynamics in patients with retinal detachment based on graph theory and machine learning.","volume":"10","author":"Wang","year":"2024","journal-title":"Heliyon"},{"key":"B37","doi-asserted-by":"publisher","first-page":"102507","DOI":"10.1016\/j.nicl.2020.102507","article-title":"An imbalance between functional segregation and integration in patients with pontine stroke: A dynamic functional network connectivity study.","volume":"28","author":"Wang","year":"2020","journal-title":"Neuroimage Clin."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e107306","DOI":"10.1371\/journal.pone.0107306","article-title":"Disrupted brain functional network in internet addiction disorder: A resting-state functional magnetic resonance imaging study.","volume":"9","author":"Wee","year":"2014","journal-title":"PLoS One"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e01656","DOI":"10.1002\/brb3.1656","article-title":"Alteration in topological properties of brain functional network after 2-year high altitude exposure: A panel study.","volume":"10","author":"Xin","year":"2020","journal-title":"Brain Behav."},{"key":"B40","doi-asserted-by":"publisher","first-page":"963634","DOI":"10.3389\/fpsyt.2022.963634","article-title":"Altered dynamic functional connectivity of auditory cortex and medial geniculate nucleus in first-episode, drug-na\u00efve schizophrenia patients with and without auditory verbal hallucinations.","volume":"13","author":"Xue","year":"2022","journal-title":"Front. Psychiatry"},{"key":"B41","article-title":"Dynamic functional connectivity variability may explain hypoxia-induced cognitive impairments at high-altitude: A 4-year longitudinal study","author":"Zeng","year":"2026","journal-title":"iScience"},{"key":"B42","doi-asserted-by":"publisher","first-page":"e68621","DOI":"10.1371\/journal.pone.0068621","article-title":"Adaptive modulation of adult brain gray and white matter to high altitude: Structural MRI studies.","volume":"8","author":"Zhang","year":"2013","journal-title":"PLoS One"},{"key":"B43","doi-asserted-by":"publisher","first-page":"915995","DOI":"10.3389\/fnhum.2022.915995","article-title":"The human brain in a high altitude natural environment: A review.","volume":"16","author":"Zhang","year":"2022","journal-title":"Front. Hum. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"788322","DOI":"10.3389\/fnagi.2022.788322","article-title":"Effects of chronic hypoxic environment on cognitive function and neuroimaging measures in a high-altitude population.","volume":"14","author":"Zhang","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11571-024-10091-3","article-title":"High-altitude exposure leads to increased modularity of brain functional network with the increased occupation of attention resources in early processing of visual working memory.","volume":"18","author":"Zhou","year":"2024","journal-title":"Cogn. Neurodyn."},{"key":"B46","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1186\/s13041-021-00827-1","article-title":"Cirbp-PSD95 axis protects against hypobaric hypoxia-induced aberrant morphology of hippocampal dendritic spines and cognitive deficits.","volume":"14","author":"Zhou","year":"2021","journal-title":"Mol. Brain"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1773258\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T05:39:52Z","timestamp":1785130792000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2026.1773258\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":46,"alternative-id":["10.3389\/fnagi.2026.1773258"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2026.1773258","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"article-number":"1773258"}}