{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:54:45Z","timestamp":1781848485398,"version":"3.54.5"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"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. Neural Circuits"],"abstract":"<jats:p>White matter lesions (WMLs) are a common cause of vascular cognitive impairment, yet the nature of whole-brain structural connectivity alterations in WML-related mild cognitive impairment (MCI) remains incompletely understood. In this study, an integrated approach combining whole-brain probabilistic fiber tracking with graph theory analysis was employed to investigate structural network changes in 33 patients with WML-related MCI and 37 healthy controls. The results revealed that, at the MCI stage, the brain\u2019s structural network exhibited not only reduced connectivity in specific neural circuits\u2013primarily fronto\u2013basal ganglia pathways\u2013but also widespread increased connectivity, particularly between the frontal lobe and other cortical regions. Group comparisons identified 50 significantly altered connections (42 increased, 8 decreased), predominantly involving cortico\u2013cortical, cortico\u2013deep gray matter, and deep gray matter\u2013deep gray matter pathways. Despite these connection-level abnormalities, no significant differences were observed in global or nodal graph-theoretical metrics. Notably, eight of the altered connections showed significant correlations with Montreal Cognitive Assessment (MoCA) scores. These structural alterations were closely associated with cognitive and behavioral deficits, indicating that they might serve as exploratory imaging indicators for WML-induced cognitive impairment.<\/jats:p>","DOI":"10.3389\/fncir.2026.1852574","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:47:14Z","timestamp":1781848034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered structural connectivity in white matter lesion-induced mild cognitive impairment: a probabilistic fiber tracking and graph theory analysis"],"prefix":"10.3389","volume":"20","author":[{"given":"An-Ming","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Ling","family":"Ma","sequence":"additional","affiliation":[{"name":"Beijing Xiaotangshan Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Xiu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-li","family":"Shi","sequence":"additional","affiliation":[{"name":"Beijing Pinggu Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Mei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Beijing Tiantan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16488","DOI":"10.1038\/s41598-019-52829-8","article-title":"Differentiation of multiple system atrophy from Parkinson\u2019s disease by structural connectivity derived from probabilistic tractography.","volume":"9","author":"Abos","year":"2019","journal-title":"Sci. Rep"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1002\/hbm.24007","article-title":"Statistical inference in brain graphs using threshold-free network-based statistics.","volume":"39","author":"Baggio","year":"2018","journal-title":"Hum. Brain Mapp"},{"key":"B3","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.neuroimage.2017.06.050","article-title":"Improved tractography using asymmetric fibre orientation distributions.","volume":"158","author":"Bastiani","year":"2017","journal-title":"Neuroimage"},{"key":"B4","doi-asserted-by":"publisher","first-page":"119600","DOI":"10.1016\/j.neuroimage.2022.119600","article-title":"Bundle-o-graphy: improving structural connectivity estimation with adaptive microstructure-informed tractography.","volume":"263","author":"Battocchio","year":"2022","journal-title":"Neuroimage"},{"key":"B5","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1042\/CS20160452","article-title":"Lesion location and cognitive impact of cerebral small vessel disease.","volume":"131","author":"Biesbroek","year":"2017","journal-title":"Clin. Sci"},{"key":"B6","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.nicl.2013.08.008","article-title":"Quantifying diffusion MRI tractography of the corticospinal tract in brain tumors with deterministic and probabilistic methods.","volume":"3","author":"Bucci","year":"2013","journal-title":"Neuroimage Clin"},{"key":"B7","doi-asserted-by":"publisher","first-page":"27736","DOI":"10.1038\/s41598-025-13813-7","article-title":"Damage to white matter networks resulting from small vessel disease and the effects on cognitive function.","volume":"15","author":"Busby","year":"2025","journal-title":"Sci. Rep"},{"key":"B8","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3389\/fnana.2018.00053","article-title":"Diffusion tensor imaging with tract-based spatial statistics reveals white matter abnormalities in patients with vascular cognitive impairment.","volume":"12","author":"Chen","year":"2018","journal-title":"Front. Neuroanat"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.3390\/biom11081102","article-title":"Role of white matter hyperintensities and related risk factors in vascular cognitive impairment: a review.","volume":"11","author":"Chen","year":"2021","journal-title":"Biomolecules"},{"key":"B10","doi-asserted-by":"publisher","first-page":"105943","DOI":"10.1016\/j.bandc.2022.105943","article-title":"Brain plasticity of structural connectivity networks and topological properties in baseball players with different levels of expertise.","volume":"166","author":"Chen","year":"2023","journal-title":"Brain Cogn"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3775","DOI":"10.1002\/hbm.25883","article-title":"Methodological evaluation of individual cognitive prediction based on the brain white matter structural connectome.","volume":"43","author":"Feng","year":"2022","journal-title":"Hum. Brain Mapp"},{"key":"B12","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1089\/brain.2020.0939","article-title":"Impaired structural connectivity in Parkinson\u2019s disease patients with mild cognitive impairment: a study based on probabilistic tractography.","volume":"11","author":"Inguanzo","year":"2021","journal-title":"Brain Connect"},{"key":"B13","doi-asserted-by":"publisher","first-page":"imag-2-00122","DOI":"10.1162\/imag_a_00122","article-title":"Functional MRI brain state occupancy in the presence of cerebral small vessel disease - a pre-registered replication analysis of the Hamburg City Health Study.","volume":"2","author":"Ingwersen","year":"2024","journal-title":"Imaging Neurosci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-981-32-9721-0_8","article-title":"Imaging connectomics and the understanding of brain diseases.","volume":"1192","author":"Insabato","year":"2019","journal-title":"Adv. Exp. Med. Biol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"675","DOI":"10.3174\/ajnr.A8530","article-title":"Evidence of small vessel disease in patients with transient global amnesia based on the peak width of skeletonized mean diffusivity.","volume":"46","author":"Lee","year":"2025","journal-title":"AJNR Am. J. Neuroradiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1515\/revneuro-2014-0082","article-title":"Genetic associations of leukoaraiosis indicate pathophysiological mechanisms in white matter lesions etiology.","volume":"26","author":"Lin","year":"2015","journal-title":"Rev. Neurosci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"130","DOI":"10.5114\/ninp.2012.28255","article-title":"Clinical application of the Polish adaptation of the Montreal Cognitive Assessment (MoCA) test in screening for cognitive impairment.","volume":"46","author":"Magierska","year":"2012","journal-title":"Neurol Neurochir. Pol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1038\/s41386-021-01152-w","article-title":"The role of PFC networks in cognitive control and executive function.","volume":"47","author":"Menon","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e774","DOI":"10.1212\/WNL.0000000000008867","article-title":"Unique white matter structural connectivity in early-stage drug-naive Parkinson disease.","volume":"94","author":"Mishra","year":"2020","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1212\/wnl.43.11.2412-a","article-title":"The Clinical Dementia Rating (CDR): current version and scoring rules.","volume":"43","author":"Morris","year":"1993","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"4265","DOI":"10.1093\/brain\/awae315","article-title":"Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment.","volume":"147","author":"Petersen","year":"2024","journal-title":"Brain"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1161\/CIRCRESAHA.122.319951","article-title":"Post-stroke cognitive impairment and dementia.","volume":"130","author":"Rost","year":"2022","journal-title":"Circ. Res"},{"key":"B23","doi-asserted-by":"publisher","first-page":"111","DOI":"10.31887\/DCNS.2018.20.2\/osporns","article-title":"Graph theory methods: applications in brain networks.","volume":"20","author":"Sporns","year":"2018","journal-title":"Dial. Clin. Neurosci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1002\/hbm.23479","article-title":"Disruption of rich club organisation in cerebral small vessel disease.","volume":"38","author":"Tuladhar","year":"2017","journal-title":"Hum. Brain Mapp"},{"key":"B25","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1136\/jnnp-2019-321767","article-title":"Structural network changes in cerebral small vessel disease.","volume":"91","author":"Tuladhar","year":"2020","journal-title":"J. Neurol Neurosurg. Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.nicl.2015.02.003","article-title":"White matter integrity in small vessel disease is related to cognition.","volume":"7","author":"Tuladhar","year":"2015","journal-title":"Neuroimage Clin"},{"key":"B27","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1177\/1073858413494269","article-title":"Dorsal and ventral attention systems: distinct neural circuits but collaborative roles.","volume":"20","author":"Vossel","year":"2014","journal-title":"Neuroscientist"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5310","DOI":"10.1002\/hbm.26004","article-title":"Superficial white matter microstructure affects processing speed in cerebral small vessel disease.","volume":"43","author":"Wang","year":"2022","journal-title":"Hum. Brain Mapp"},{"key":"B29","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/S1474-4422(13)70124-8","article-title":"Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"350","DOI":"10.4103\/jnrp.jnrp_542_17","article-title":"The role of brain magnetic resonance imaging (MRI) as an early detector of cognitive impairment.","volume":"9","author":"Yueniwati","year":"2018","journal-title":"J. Neurosci. Rural Pract"}],"container-title":["Frontiers in Neural Circuits"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2026.1852574\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:47:15Z","timestamp":1781848035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncir.2026.1852574\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,19]]},"references-count":30,"alternative-id":["10.3389\/fncir.2026.1852574"],"URL":"https:\/\/doi.org\/10.3389\/fncir.2026.1852574","relation":{},"ISSN":["1662-5110"],"issn-type":[{"value":"1662-5110","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,19]]},"article-number":"1852574"}}