{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:00:54Z","timestamp":1789441254763,"version":"build-2803163510"},"reference-count":69,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, with cognitive dysfunction being one of its most common neuropsychiatric manifestations. Cognitive flexibility relies on the integration of brain structure and function, with white matter networks providing anatomical constraints for functional dynamics. Reduced cognitive flexibility is frequently observed in SLE, but the underlying structure\u2013function integration\u00a0changes remain poorly understood. This study investigated whether brain structure\u2013function integration is altered in SLE and how it links to cognitive flexibility. We examined 22 SLE patients without clinically overt neuropsychiatric manifestation (age: 34.99\u2009\u00b1\u200910.67; 18 females) and 60 healthy controls (HCs) (age: 28.43\u2009\u00b1\u20098.56; 29 females). Using diffusion MRI and task\u2010based fMRI acquired during the Montreal Card Sorting Test (MCST), a cognitive flexibility task, we derived brain structural\u2013functional alignment and liberality, which quantify the extent to which brain functional signals are either coupled with or deviate from the underlying anatomical network. We found SLE patients exhibited globally higher liberality and lower alignment compared to HCs, and this was driven by the disrupted structure\u2013function integration in the executive control network (ECN). The ECN comprises three subnetworks: ECN\u2010A and ECN\u2010B comprise key lateral fronto\u2010parietal executive control areas, while ECN\u2010C is anatomically closer to the default mode network. Further analyses revealed that SLE had higher liberality in ECN\u2010A and ECN\u2010B regions, alongside lower alignment in ECN\u2010A, while ECN\u2010C did not show these alterations. Importantly, increased liberality and decreased alignment in the ECN regions were associated with poorer cognitive flexibility (MCST performance) in SLE participants. This association was also observed across all participants. In SLE individuals specifically, liberality and alignment in the fronto\u2010parietal ECN were further linked to clinical variables, including serum albumin and corticosteroid dosage. Additionally, the liberality and alignment in the ECN and its subnetworks were associated with cognitive performance outside the scanner (measured by Automated Neuropsychological Assessment Metrics) across all participants. Our findings suggest that aberrant structure\u2013function integration, particularly within the fronto\u2010parietal ECN, impacts cognitive flexibility and may contribute to the development of cognitive impairment in SLE.<\/jats:p>","DOI":"10.1002\/hbm.70299","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T06:49:46Z","timestamp":1758610186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disrupted Structure\u2013Function Integration in Systemic Lupus Erythematosus and Its Impact on Cognitive Flexibility"],"prefix":"10.1002","volume":"46","author":[{"given":"Xing","family":"Qian","sequence":"first","affiliation":[{"name":"Centre for Sleep and Cognition &amp; Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6183-4493","authenticated-orcid":false,"given":"Dani S.","family":"Bassett","sequence":"additional","affiliation":[{"name":"Department of Physics &amp; Astronomy University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Bioengineering University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Electrical &amp; Systems Engineering University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Neurology University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwun Kei","family":"Ng","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition &amp; Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice R. Y.","family":"Loo","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition &amp; Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine National University of Singapore  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger Chun\u2010man","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselm","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Medicine National University Hospital  Singapore Singapore"},{"name":"Division of Rheumatology &amp; Allergy, Department of Medicine Yong Loo Lin School of Medicine, National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0180-8648","authenticated-orcid":false,"given":"Juan Helen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Centre for Sleep and Cognition &amp; Centre for Translational Magnetic Resonance Research, Yong Loo Lin School of Medicine National University of Singapore  Singapore"},{"name":"Department of Medicine Yong Loo Lin School of Medicine, National University of Singapore  Singapore Singapore"},{"name":"Department of Electrical and Computer Engineering National University of Singapore  Singapore Singapore"},{"name":"Integrative Sciences and Engineering Programme (ISEP) National University of Singapore  Singapore Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.21187"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2024.152620"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2018-214677"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1912034117"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.10609"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1037\/a0017767"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-8624.2010.01499.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780350606"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2019.03.073"},{"issue":"2","key":"e_1_2_8_11_1","doi-asserted-by":"crossref","DOI":"10.1136\/lupus-2024-001214","article-title":"Effects of Systemic Lupus Erythematosus on the Brain: A Systematic Review of Structural MRI Findings and Their Relationships With Cognitive Dysfunction","volume":"11","author":"Cabrera D. 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