{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T01:46:29Z","timestamp":1767836789588,"version":"3.49.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"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:sec><jats:title>Purpose<\/jats:title><jats:p>The purpose of the study was to investigate the brain functional alteration in patients with thyroid-associated ophthalmopathy (TAO) by evaluating the spontaneous neural activity changes using resting-state functional magnetic resonance imaging (rs-fMRI) with the amplitude of low-frequency fluctuation (ALFF) method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>The rs-fMRI data of 30 TAO patients (15 active and 15 inactive) and 15 healthy controls (HCs) were included for analyses. The ALFF values were calculated and compared among groups. Correlations between ALFF values and clinical metrics were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with HCs, active TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, and cuneus. Compared with inactive TAOs, active TAOs showed significantly increased ALFF values in the bilateral precuneus. Additionally, inactive TAOs showed significantly decreased ALFF values in the left middle occipital gyrus, superior occipital gyrus, cuneus, and bilateral precuneus than HCs. The ALFF value in the right precuneus of TAOs was positively correlated with clinical activity score (<jats:italic>r<\/jats:italic> = 0.583, <jats:italic>P<\/jats:italic> &amp;lt; 0.001) and Mini-Mental State Examination (MMSE) score (<jats:italic>r<\/jats:italic> = 0.377, <jats:italic>P<\/jats:italic> = 0.040), and negatively correlated with disease duration (<jats:italic>r<\/jats:italic> = \u22120.382, <jats:italic>P<\/jats:italic> = 0.037). Moreover, the ALFF value in the left middle occipital gyrus of TAOs was positively correlated with visual acuity (<jats:italic>r<\/jats:italic> = 0.441, <jats:italic>P<\/jats:italic> = 0.015).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>TAO patients had altered spontaneous brain activities in the left occipital lobe and bilateral precuneus. The neuropsychological aspect of the disease should be noticed during clinical diagnosis and treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnhum.2021.676967","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:02:43Z","timestamp":1623409363000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Disrupted Spontaneous Neural Activity in Patients With Thyroid-Associated Ophthalmopathy: A Resting-State fMRI Study Using Amplitude of Low-Frequency Fluctuation"],"prefix":"10.3389","volume":"15","author":[{"given":"Wen","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan-Huan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Quan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fei-Yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/j.neuroimage.2011.10.025","article-title":"SPM: a history.","volume":"62","author":"Ashburner","year":"2012","journal-title":"Neuroimage"},{"key":"B2","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1056\/NEJMra0905750","article-title":"Graves\u2019 ophthalmopathy.","volume":"362","author":"Bahn","year":"2010","journal-title":"N Engl J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"583931","DOI":"10.1155\/2015\/583931","article-title":"Precuneus and Cingulate Cortex Atrophy and Hypometabolism in Patients with Alzheimer\u2019s Disease and Mild Cognitive Impairment: MRI and (18)F-FDG PET Quantitative Analysis Using FreeSurfer.","volume":"2015","author":"Bailly","year":"2015","journal-title":"Biomed Res Int"},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000443828","article-title":"The 2016 European Thyroid Association\/European Group on Graves\u2019 Orbitopathy Guidelines for the Management of Graves\u2019 Orbitopathy.","volume":"5","author":"Bartalena","year":"2016","journal-title":"Eur Thyroid J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1111\/j.1365-2826.2008.01774.x","article-title":"The thyroid-brain interaction in thyroid disorders and mood disorders.","volume":"20","author":"Bauer","year":"2008","journal-title":"J Neuroendocrinol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1016\/j.neuroimage.2012.01.090","article-title":"Resting state fMRI: a personal history.","volume":"62","author":"Biswal","year":"2012","journal-title":"Neuroimage"},{"key":"B7","doi-asserted-by":"publisher","first-page":"w13786","DOI":"10.4414\/smw.2013.13786","article-title":"The impact of emotion on perception, attention, memory, and decision-making.","volume":"143","author":"Brosch","year":"2013","journal-title":"Swiss Med Wkly"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1196\/annals.1440.011","article-title":"The brain\u2019s default network: anatomy, function, and relevance to disease.","volume":"1124","author":"Buckner","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"B9","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1093\/brain\/awl004","article-title":"The precuneus: a review of its functional anatomy and behavioural correlates.","volume":"129","author":"Cavanna","year":"2006","journal-title":"Brain"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.2147\/NDT.S134258","article-title":"Primary angle-closure glaucomas disturb regional spontaneous brain activity in the visual pathway: an fMRI study.","volume":"13","author":"Chen","year":"2017","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B11","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1530\/EJE-07-0205","article-title":"Psychological implications of Graves\u2019 orbitopathy.","volume":"157","author":"Coulter","year":"2007","journal-title":"Eur J Endocrinol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"3681430","DOI":"10.1155\/2019\/3681430","article-title":"Altered Spontaneous Brain Activity of Children with Unilateral Amblyopia: A Resting State fMRI Study.","volume":"2019","author":"Dai","year":"2019","journal-title":"Neural Plast"},{"key":"B13","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ando.2018.08.005","article-title":"Graves\u2019 orbitopathy: Diagnosis and treatment.","volume":"79","author":"Drui","year":"2018","journal-title":"Ann Endocrinol (Paris)"},{"key":"B14","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.neurol.2018.03.003","article-title":"Impairment of social cognition in neurological diseases.","volume":"174","author":"Duclos","year":"2018","journal-title":"Rev Neurol (Paris)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"7900","DOI":"10.1073\/pnas.1602413113","article-title":"Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates.","volume":"113","author":"Eklund","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B16","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1111\/j.1365-2265.2007.03087.x","article-title":"The impact of thyroid eye disease upon patients\u2019 wellbeing: a qualitative analysis.","volume":"68","author":"Estcourt","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"key":"B17","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1001\/archopht.123.4.491","article-title":"Psychological disturbance in graves ophthalmopathy.","volume":"123","author":"Farid","year":"2005","journal-title":"Arch Ophthalmol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1089\/thy.2017.0365","article-title":"Death by Suicide in Graves\u2019 Disease and Graves\u2019 Orbitopathy: A Nationwide Danish Register Study.","volume":"27","author":"Ferlov-Schwensen","year":"2017","journal-title":"Thyroid"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1178","DOI":"10.1016\/j.neuroimage.2008.05.059","article-title":"The precuneus\/posterior cingulate cortex plays a pivotal role in the default mode network: Evidence from a partial correlation network analysis.","volume":"42","author":"Fransson","year":"2008","journal-title":"Neuroimage"},{"key":"B20","doi-asserted-by":"publisher","first-page":"180245","DOI":"10.1503\/jpn.180245","article-title":"Abnormalities of intrinsic regional brain activity in first-episode and chronic schizophrenia: a meta-analysis of resting-state functional MRI.","volume":"44","author":"Gong","year":"2019","journal-title":"J Psychiatry Neurosci"},{"key":"B21","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1007\/s00266-011-9843-4","article-title":"The diagnosis and treatment of thyroid-associated ophthalmopathy.","volume":"36","author":"Gould","year":"2012","journal-title":"Aesthetic Plast Surg"},{"key":"B22","doi-asserted-by":"publisher","first-page":"353","DOI":"10.2169\/internalmedicine.53.1518","article-title":"Graves\u2019 ophthalmopathy: epidemiology and natural history.","volume":"53","author":"Hiromatsu","year":"2014","journal-title":"Intern Med"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.5114\/aoms.2019.87133","article-title":"Altered brain network centrality in patients with late monocular blindness: a resting-state fMRI study.","volume":"15","author":"Huang","year":"2019","journal-title":"Arch Med Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/s1053-8119(02)91132-8","article-title":"Improved optimization for the robust and accurate linear registration and motion correction of brain images.","volume":"17","author":"Jenkinson","year":"2002","journal-title":"Neuroimage"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e0227021","DOI":"10.1371\/journal.pone.0227021","article-title":"Percent amplitude of fluctuation: A simple measure for resting-state fMRI signal at single voxel level.","volume":"15","author":"Jia","year":"2020","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.scib.2019.05.008","article-title":"RESTplus: an improved toolkit for resting-state functional magnetic resonance imaging data processing.","volume":"64","author":"Jia","year":"2019","journal-title":"Science Bulletin"},{"key":"B27","doi-asserted-by":"publisher","first-page":"271","DOI":"10.2147\/NDT.S187367","article-title":"Frequency-dependent neural activity in primary angle-closure glaucoma.","volume":"15","author":"Jiang","year":"2019","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B28","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1089\/105072502753600205","article-title":"Psychosocial factors in subjects with thyroid-associated ophthalmopathy.","volume":"12","author":"Kahaly","year":"2002","journal-title":"Thyroid"},{"key":"B29","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1002\/da.22478","article-title":"Aberrant Resting-State Brain Activity in Posttraumatic Stress Disorder: A Meta-Analysis and Systematic Review.","volume":"33","author":"Koch","year":"2016","journal-title":"Depress Anxiety"},{"key":"B30","first-page":"250","article-title":"Resting state in obsessive-compulsive disorder. A review of the literature.","volume":"42","author":"Leon","year":"2014","journal-title":"Actas Esp Psiquiatr"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/j.jfma.2013.12.002","article-title":"Assessing quality of life in Taiwanese patients with Graves\u2019 ophthalmopathy.","volume":"114","author":"Lin","year":"2015","journal-title":"J Formos Med Assoc"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0167279","DOI":"10.1371\/journal.pone.0167279","article-title":"Amplitude of Low Frequency Fluctuation (ALFF) in the Cervical Spinal Cord with Stenosis: A Resting State fMRI Study.","volume":"11","author":"Liu","year":"2016","journal-title":"PLoS One"},{"key":"B33","doi-asserted-by":"publisher","first-page":"6827","DOI":"10.1073\/pnas.0400049101","article-title":"Parietal cortex and representation of the mental Self.","volume":"101","author":"Lou","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1002\/jmri.26708","article-title":"Altered cortical morphology of visual cortex in adults with monocular amblyopia.","volume":"50","author":"Lu","year":"2019","journal-title":"J Magn Reson Imaging"},{"key":"B35","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.neuroimage.2005.05.008","article-title":"The role of precuneus and left inferior frontal cortex during source memory episodic retrieval.","volume":"27","author":"Lundstrom","year":"2005","journal-title":"Neuroimage"},{"key":"B36","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1007\/s11682-017-9680-4","article-title":"Alteration of regional homogeneity and white matter hyperintensities in amnestic mild cognitive impairment subtypes are related to cognition and CSF biomarkers.","volume":"12","author":"Luo","year":"2018","journal-title":"Brain Imaging Behav"},{"key":"B37","doi-asserted-by":"publisher","first-page":"24","DOI":"10.3389\/fnins.2019.00024","article-title":"The Local Brain Abnormalities in Patients With Transient Ischemic Attack: A Resting-State fMRI Study.","volume":"13","author":"Lv","year":"2019","journal-title":"Front Neurosci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"89","DOI":"10.3389\/fnbeh.2019.00089","article-title":"Altered Resting-State Functional Activity in Medication-Naive Patients With First-Episode Major Depression Disorder vs. Healthy Control: A Quantitative Meta-Analysis.","volume":"13","author":"Ma","year":"2019","journal-title":"Front Behav Neurosci"},{"key":"B39","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.arr.2016.12.001","article-title":"Aberrant spontaneous low-frequency brain activity in amnestic mild cognitive impairment: A meta-analysis of resting-state fMRI studies.","volume":"35","author":"Pan","year":"2017","journal-title":"Ageing Res Rev"},{"key":"B40","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1136\/bjo.88.1.75","article-title":"Assessing quality of life in Australian patients with Graves\u2019 ophthalmopathy.","volume":"88","author":"Park","year":"2004","journal-title":"Br J Ophthalmol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1007\/s11910-014-0448-6","article-title":"Resting state functional magnetic resonance imaging in Parkinson\u2019s disease.","volume":"14","author":"Prodoehl","year":"2014","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B42","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.maturitas.2015.03.016","article-title":"Thyroid hormone: Influences on mood and cognition in adults.","volume":"81","author":"Ritchie","year":"2015","journal-title":"Maturitas"},{"key":"B43","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1097\/ICU.0000000000000596","article-title":"Update on the clinical assessment and management of thyroid eye disease.","volume":"30","author":"Roos","year":"2019","journal-title":"Curr Opin Ophthalmol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"94","DOI":"10.4274\/tjo.80688","article-title":"Thyroid-associated Ophthalmopathy.","volume":"47","author":"Sahli","year":"2017","journal-title":"Turk J Ophthalmol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/j.1475-097X.2009.00858.x","article-title":"Differences between smooth pursuit and optokinetic eye movements using limited lifetime dot stimulation: a functional magnetic resonance imaging study.","volume":"29","author":"Schraa-Tam","year":"2009","journal-title":"Clin Physiol Funct Imaging"},{"key":"B46","first-page":"T9","article-title":"Neuroanatomic Variations in Graves\u2019 Dysthyroid Ophthalmopathy as Studied With MRI.","volume":"114","author":"Silkiss","year":"2016","journal-title":"Trans Am Ophthalmol Soc"},{"key":"B47","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1007\/s00702-017-1710-2","article-title":"Clinical utility of resting-state functional connectivity magnetic resonance imaging for mood and cognitive disorders.","volume":"124","author":"Takamura","year":"2017","journal-title":"J Neural Transm (Vienna)"},{"key":"B48","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1523\/JNEUROSCI.4227-13.2014","article-title":"Precuneus is a functional core of the default-mode network.","volume":"34","author":"Utevsky","year":"2014","journal-title":"J Neurosci"},{"key":"B49","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/eye.2015.76","article-title":"Which factors are associated with quality of life in patients with Graves\u2019 orbitopathy presenting for orbital decompression surgery?","volume":"29","author":"Wickwar","year":"2015","journal-title":"Eye (Lond)"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1007\/s40618-020-01242-4","article-title":"Morphological and microstructural brain changes in thyroid-associated ophthalmopathy: a combined voxel-based morphometry and diffusion tensor imaging study.","volume":"43","author":"Wu","year":"2020","journal-title":"J Endocrinol Invest"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e68910","DOI":"10.1371\/journal.pone.0068910","article-title":"BrainNet Viewer: a network visualization tool for human brain connectomics.","volume":"8","author":"Xia","year":"2013","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s12021-016-9299-4","article-title":"DPABI: Data Processing & Analysis for (Resting-State) Brain Imaging.","volume":"14","author":"Yan","year":"2016","journal-title":"Neuroinformatics"},{"key":"B53","first-page":"368","article-title":"Quality of life in patients with Graves ophthalmopathy.","volume":"103","author":"Yeatts","year":"2005","journal-title":"Trans Am Ophthalmol Soc"},{"key":"B54","first-page":"1541","article-title":"Difference in resting-state fractional amplitude of low-frequency fluctuation between bipolar depression and unipolar depression patients.","volume":"21","author":"Yu","year":"2017","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"B55","doi-asserted-by":"publisher","first-page":"9408612","DOI":"10.1155\/2019\/9408612","article-title":"Altered Amplitude of Low-Frequency Fluctuations in Inactive Patients with Nonneuropsychiatric Systemic Lupus Erythematosus.","volume":"2019","author":"Yu","year":"2019","journal-title":"Neural Plast"},{"key":"B56","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.braindev.2006.07.002","article-title":"Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI.","volume":"29","author":"Zang","year":"2007","journal-title":"Brain Dev"},{"key":"B57","doi-asserted-by":"publisher","first-page":"7602419","DOI":"10.1155\/2019\/7602419","article-title":"Evaluation of the Graves\u2019 Orbitopathy-Specific Quality of Life Questionnaire in the Mainland Chinese Population.","volume":"2019","author":"Zeng","year":"2019","journal-title":"J Ophthalmol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.3389\/fninf.2018.00054","article-title":"Intra- and Inter-Scanner Reliability of Voxel-Wise Whole-Brain Analytic Metrics for Resting State fMRI.","volume":"12","author":"Zhao","year":"2018","journal-title":"Front Neuroinform"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1642087","DOI":"10.1155\/2019\/1642087","article-title":"The Association between DRD3 Ser9Gly Polymorphism and Depression Severity in Parkinson\u2019s Disease.","volume":"2019","author":"Zhi","year":"2019","journal-title":"Parkinsons Dis"},{"key":"B60","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1016\/j.biopsych.2011.10.035","article-title":"Evidence of a dissociation pattern in resting-state default mode network connectivity in first-episode, treatment-naive major depression patients.","volume":"71","author":"Zhu","year":"2012","journal-title":"Biol Psychiatry"},{"key":"B61","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.jneumeth.2008.04.012","article-title":"An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF.","volume":"172","author":"Zou","year":"2008","journal-title":"J Neurosci Methods"}],"container-title":["Frontiers in Human Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2021.676967\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T11:02:51Z","timestamp":1623409371000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnhum.2021.676967\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,11]]},"references-count":61,"alternative-id":["10.3389\/fnhum.2021.676967"],"URL":"https:\/\/doi.org\/10.3389\/fnhum.2021.676967","relation":{},"ISSN":["1662-5161"],"issn-type":[{"value":"1662-5161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,11]]},"article-number":"676967"}}