Lesions Associated With Autism Symptoms Map to a Cerebellar Brain Network in Tuberous Sclerosis Complex
Year: 2025
Type: article
Study design: Observational Study
Abstract: Objective: 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-based model to investigate the neural circuits underlying ASD symptoms. We tested whether tuber connectivity is associated with specific ASD symptom profiles in TSC patients. Methods: 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-state functional magnetic resonance imaging data from 1000 typically developing 9-year-olds 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). Results: 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. Interpretation: Social affect impairments in TSC patients with ASD are associated with to functional connectivity between tubers and cerebellar crus V. This symptom-specific neuroanatomical association supports the concept that different ASD features map to distinct brain circuits and highlights the role of cortico-cerebellar pathways in early social development.
DOI: 10.1002/cns3.70045
Institutions: Boston Children's Hospital, Harvard University, Cincinnati Children's Hospital Medical Center, University of Alabama at Birmingham, UAB Medicine, Memorial Hermann, Memorial Hermann–Texas Medical Center, The University of Texas Health Science Center at Houston, Northwestern University, Lurie Children's Hospital, Brigham and Women's Hospital, Massachusetts General Hospital, Athinoula A. Martinos Center for Biomedical Imaging
Language: English
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,000
Awards: G1020259976, G1742849658, G1778125652, G2446786914, G2715786902, Improved Motion Robust MRI of Children, G3563224455, G3830015915, Early Biomarkers of Autism Spectrum Disorders in infants with Tuberous Sclerosis, G4066048162, G5081895789, G5139799579, CH/BIDMC/Harvard Medical School Neurology Resident Research Education Program, Machine learning algorithms to analyze large medical image datasets, Identifying neuromodulation targets for pain in the human brain, G687916792, G6887863799, G6912864445, G6922259526, G7271102572, G7562459834, G7652160222, G771167098, G8679417706, G8762821959, G8865478933, 9/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT U MICHIGAN, 17/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UCLA, 8/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT CHLA, 6/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT OHSU, Using Brain Lesions and Deep Brain Stimulation to Identify an Epilepsy Circuit, Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive Disorder, 21/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT WUSTL, BRAIN CONNECTS: The center for Large-scale Imaging of Neural Circuits (LINC), 2/21 ABCD-USA CONSORTIUM: RESEARCH PROJECT SITE AT UMB, Motion Compensated fMRI for Pre-Surgical Planning in Epilepsy, G923039674
OpenAlex ID: W4417289995