Abstract Details

Title Functional Connectivity Between Tubers and the Somatomotor Areas and Cerebellum Is Associated with Impaired Social Affect in Tuberous Sclerosis Complex

Topic Child Neurology and Developmental Neurology

Presentation(s) S8 - State-of-the-art Diagnostics in Child Neurology (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

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.

Objective To Identify whether tuber involvement of specific brain networks is associated with autism severity and/or distinct autism phenotypes in tuberous sclerosis complex

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.

Authors/Disclosures
Wendy X. Herman, MD, PhD (Child Neurology Boston Children's Hospital) PRESENTER	Dr. Herman has nothing to disclose.
Gillian Miller (Boston Children's Hospital)	Ms. Miller has nothing to disclose.
William Drew (Brigham and Women's Hospital)	Mr. Drew has nothing to disclose.
Jurriaan Peters, MD (Boston Childrens Hospital)	Dr. Peters has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurelis. Dr. Peters has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurelis. Dr. Peters has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for Neurelis.
Simon Warfield	No disclosure on file
Mustafa Sahin, MD, PhD (Boston Children'S Hospital)	Dr. Sahin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Regenxbio . Dr. Sahin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Centene. Dr. Sahin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene. Dr. Sahin has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for PTEN Research. Dr. Sahin has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Sahin has received research support from NIH. The institution of Dr. Sahin has received research support from Tuberous Sclerosis Alliance. The institution of Dr. Sahin has received research support from Charities Aid Foundation. The institution of Dr. Sahin has received research support from Simons Foundation Autism Research Initiative. The institution of Dr. Sahin has received research support from Aucta Pharmaceuticals . The institution of Dr. Sahin has received research support from Loulou Foundation.
Darcy Krueger, MD (Cincinnati Children'S Hospital Medical Center)	Dr. Krueger has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NobelPharma USA. Dr. Krueger has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for RegenxBio. Dr. Krueger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis Pharmaceuticals. Dr. Krueger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Greenwich Biosciences. The institution of Dr. Krueger has received research support from Greenwich Bioscience. The institution of Dr. Krueger has received research support from Marinus Pharmaceuticals. The institution of Dr. Krueger has received research support from National Institutes of Health. The institution of Dr. Krueger has received research support from Food and Drug Administration. The institution of Dr. Krueger has received research support from TSC Alliance.
E M. Bebin, MD, FAAN (UAB Epilepsy Center)	Dr. Bebin has received personal compensation for serving as an employee of Springworks Therapeutics. Dr. Bebin has received personal compensation for serving as an employee of Apertura Gene Therapy. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springworks Therapeutics. Dr. Bebin has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Apertura. The institution of Dr. Bebin has received research support from NINDS. The institution of Dr. Bebin has received research support from FDA Orphan Drug Program.
Hope Northrup	No disclosure on file
Joyce Y. Wu, MD (Lurie Children's Hospital)	Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocodex. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Marinus. The institution of Dr. Wu has received research support from National Institutes of Health. Dr. Wu has received personal compensation in the range of $500-$4,999 for serving as a Study section member with National Institutes of Health.
Michael D. Fox, MD, PhD (Brigham and Women's Hospital / Harvard Medical School)	Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley.
Alexander L. Cohen, MD, PhD, FAAN (Boston Children's Hospital)	The institution of Dr. Cohen has received research support from NIH. The institution of Dr. Cohen has received research support from Simons Foundation.