{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T22:51:15Z","timestamp":1782859875916,"version":"3.54.5"},"reference-count":33,"publisher":"SAGE Publications","issue":"5-6","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K23NS119666"],"award-info":[{"award-number":["K23NS119666"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["U01NS082320"],"award-info":[{"award-number":["U01NS082320"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:p>Background: Abnormalities in white matter development may influence development of autism spectrum disorder in tuberous sclerosis complex (TSC). Our goals for this study were as follows: (1) use data from a longitudinal neuroimaging study of tuberous sclerosis complex (TACERN) to develop optimized linear mixed effects models for analyzing longitudinal, repeated diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity) pertaining to select white matter tracts, in relation to positive Autism Diagnostic Observation Schedule\u2013Second Edition classification at 36 months, and (2) perform an exploratory analysis using optimized models applied to all white matter tracts from these data. Methods: Eligible participants (3-12 months) underwent brain magnetic resonance imaging (MRI) at repeated time points from ages 3 to 36 months. Positive Autism Diagnostic Observation Schedule\u2013Second Edition classification at 36 months was used. Linear mixed effects models were fine-tuned separately for fractional anisotropy values (using fractional anisotropy corpus callosum as test outcome) and mean diffusivity values (using mean diffusivity right posterior limb internal capsule as test outcome). Fixed effects included participant age, within-participant longitudinal age, and autism spectrum disorder diagnosis. Results: Analysis included data from n\u2009=\u200978. After selecting separate optimal models for fractional anisotropy and mean diffusivity values, we applied these models to fractional anisotropy and mean diffusivity of all 27 white matter tracts. Fractional anisotropy corpus callosum was related to positive Autism Diagnostic Observation Schedule\u2013Second Edition classification (coefficient\u2009=\u20090.0093, P\u2009=\u2009.0612), and mean diffusivity right inferior cerebellar peduncle was related to positive Autism Diagnostic Observation Schedule\u2013Second Edition classification (coefficient\u2009=\u2009\u20130.00002071, P\u2009=\u2009.0445), though these findings were not statistically significant after multiple comparisons correction. Conclusion: These optimized linear mixed effects models possibly implicate corpus callosum and cerebellar pathology in development of autism spectrum disorder in tuberous sclerosis complex, but future studies are needed to replicate these findings and explore contributors of heterogeneity in these models.<\/jats:p>","DOI":"10.1177\/08830738241248685","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T02:13:11Z","timestamp":1715825591000},"page":"178-189","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Abnormality of Early White Matter Development in Tuberous Sclerosis Complex and Autism Spectrum Disorder: Longitudinal Analysis of Diffusion Tensor Imaging Measures"],"prefix":"10.1177","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"first","affiliation":[{"name":"Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanghan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Prohl","sequence":"additional","affiliation":[{"name":"Computational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5796-6015","authenticated-orcid":false,"given":"Peter E.","family":"Davis","sequence":"additional","affiliation":[{"name":"Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie K.","family":"Capal","sequence":"additional","affiliation":[{"name":"Carolina Institute for Developmental Disabilities, Carrboro, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajna","family":"Filip-Dhima","sequence":"additional","affiliation":[{"name":"Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. Martina","family":"Bebin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Alabama School of Medicine, Birmingham, AL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darcy A.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Division of Neurology, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hope","family":"Northrup","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children's Memorial Hermann Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon K.","family":"Warfield","sequence":"additional","affiliation":[{"name":"Computational Radiology Laboratory, Department of Radiology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7044-2953","authenticated-orcid":false,"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Rosamund Stone Zander Translational Neuroscience Center, Department of Neurology, Boston Children's Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1574-198X","authenticated-orcid":false,"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology and ICCTR Biostatistics and Research Design Center, Boston Children\u2019s Hospital, Harvard Medical School, Boston, 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