Functional Connectivity Between Tubers and the Somatomotor Areas and Cerebellum Is Associated with Impaired Social Affect in Tuberous Sclerosis Complex
Wendy Herman1, Gillian Miller2, William Drew4, Jurriaan Peters2, Simon Warfield3, Mustafa Sahin2, Darcy Krueger5, E Bebin6, Hope Northrup7, Joyce Wu8, Michael Fox4, Alexander Cohen2
1Child Neurology Boston Children's Hospital, 2Neurology, 3Radiology, Boston Children's Hospital, 4Brigham and Women's Hospital / Harvard Medical School, 5Cincinnati Children's Hospital Medical Center, 6UAB Epilepsy Center, 7University of Texas Houston, 8Lurie Children's Hospital
Objective:
To Identify whether tuber involvement of specific brain networks is associated with autism severity and/or distinct autism phenotypes in tuberous sclerosis complex
Background:
Autism spectrum disorder (ASD) is a neurodevelopmental condition affecting 1:54 people that results in altered social communication and restrictive/repetitive behavior, interests, and activities. While the neuroanatomy of ASD remains unclear, individuals with Tuberous Sclerosis Complex (TSC) are at risk of developing ASD (40%) and have focal brain lesions that affect surrounding brain function. Because TSC-related ASD is indistinguishable from idiopathic/non-syndromic ASD, studying TSC may provide unique insights into the neuroanatomical substrate of ASD.
Design/Methods:
Here, we leverage consortium-level data from the TSC Autism Centers of Excellence Research Network (TACERN) including 115 participants with research-reliable Autism Diagnostic Observation Schedule (ADOS) and structural neuroimaging data. Using lesion network mapping, a technique that identifies functional brain circuits associated with lesions, e.g., cortical tubers, we correlate specific ADOS variables with tuber-connected networks leveraging normative data from 1000 9-year-olds from the Adolescent Brain Cognitive Development Study.
Results:
We found minimal localization of tuber networks correlated with overall scaled autism severity. However, simultaneously modeling social affect (SA) and repetitive restrictive behaviors (RRB) subscores revealed that SA scores were correlated with increased functional connectivity to bilateral cerebellar deep nuclei and the bilateral somatomotor areas. We also found that variance associated with RRB severity appeared largely orthogonal to SA, consistent with the distinction between these behavioral domains.
Conclusions:
We found that social affect strongly correlates with tuber involvement of a specific network connected to the bilateral somatomotor and cerebellar areas. This effect is less robust when using total ADOS scores, which may help explain why neuroimaging research leveraging total autism severity has produced heterogenous results. Our findings indicate a specific brain network related to social affect in TSC-related autism, which may be relevant for idiopathic/non-syndromic ASD as well.