{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T19:36:15Z","timestamp":1773776175148,"version":"3.50.1"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Autism spectrum disorder (ASD) affects 1 in 36 individuals in the United States and is characterized by impaired social communication and restrictive\/repetitive behaviors. Individuals with tuberous sclerosis complex (TSC) have a high incidence of ASD (40%) and exhibit congenital brain lesions (tubers), offering a unique lesion\u2010based model to investigate the neural circuits underlying ASD symptoms. We tested whether tuber connectivity is associated with specific ASD symptom profiles in TSC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Brain tuber locations were analyzed in 115 children with TSC from the TSC Autism Centers of Excellence Research Network. Lesion network mapping was performed using normative resting\u2010state functional magnetic resonance imaging data from 1000 typically developing 9\u2010year\u2010olds to identify brain networks functionally connected to tuber locations. Multivariable linear regression analyses assessed associations between these networks and specific domain subscores on the Autism Diagnostic Observation Schedule (ADOS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Greater severity of social affect symptoms was associated with tubers connected to bilateral deep cerebellar nuclei, particularly the right side, localizing to Crus V despite no cerebellar tubers being included in this analysis. No significant associations were found for total ADOS scores or repetitive\/restrictive behavior subscores. These effects were independent of age, sex, lesion burden, epilepsy severity, and language ability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Social affect impairments in TSC patients with ASD are associated with to functional connectivity between tubers and cerebellar crus V. This symptom\u2010specific neuroanatomical association supports the concept that different ASD features map to distinct brain circuits and highlights the role of cortico\u2010cerebellar pathways in early social development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70045","type":"journal-article","created":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T02:26:32Z","timestamp":1765592792000},"page":"64-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lesions Associated With Autism Symptoms Map to a Cerebellar Brain Network in Tuberous Sclerosis Complex"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1643-5653","authenticated-orcid":false,"given":"Wendy Xiao","family":"Herman","sequence":"first","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian N.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Sahin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Rosamund Stone Zander Translational Neuroscience Center, Boston Children's Hospital, Harvard Medical School Harvard University Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jurriaan M.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Neurology, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Radiology, Computational Radiology Laboratory, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon K.","family":"Warfield","sequence":"additional","affiliation":[{"name":"Department of Radiology, Computational Radiology Laboratory, Boston Children's Hospital Harvard Medical School Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darcy A.","family":"Krueger","sequence":"additional","affiliation":[{"name":"Department of Neurology Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. Martina","family":"Bebin","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce Y.","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Neurology &amp; Epilepsy, Ann &amp; Robert H. Lurie Children's Hospital of Chicago Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8848-6399","authenticated-orcid":false,"given":"Michael D.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center for Brain Circuit Therapeutics, Brigham and Women's Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Neurology, Massachusetts General Hospital Harvard Medical School Boston Massachusetts USA"},{"name":"Department of Radiology, Athinoula A. 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