Abstract
Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by benign tumors throughout the body; it is generally diagnosed early in life and has a high prevalence of autism spectrum disorder (ASD), making it uniquely valuable in studying the early development of autism, before neuropsychiatric symptoms become apparent. One well-documented deficit in ASD is an impairment in face processing. In this work, we assessed whether anatomical connectivity patterns of the fusiform gyrus, a central structure in face processing, capture the risk of developing autism early in life. We longitudinally imaged TSC patients at 1, 2, and 3 years of age with diffusion compartment imaging. We evaluated whether the anatomical connectivity fingerprint of the fusiform gyrus was associated with the risk of developing autism measured by the Autism Observation Scale for Infants (AOSI). Our findings suggest that the fusiform gyrus connectivity captures the risk of developing autism as early as 1 year of age and provides evidence that abnormal fusiform gyrus connectivity increases with age. Moreover, the identified connections that best capture the risk of developing autism involved the fusiform gyrus and limbic and paralimbic regions that were consistent with the ASD phenotype, involving an increased number of left-lateralized structures with increasing age.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2199-2214 |
| Number of pages | 16 |
| Journal | Cerebral Cortex |
| Volume | 30 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 14 2020 |
Funding
National Institutes of Health (grants U01 NS082320, R01 NS 079788, R01 EB019483, R01 EB013248, U54 NS092090, and U54 HD090255); Developmental Synaptopathies Consortium (U54NS092090), which is a part of the NCATS Rare Diseases Clinical Research Network (RDCRN); RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), National Center for Advancing Translational Sciences (NCATS), funded through collaboration between NCATS, National Institute of Mental Health, NINDS and National Institute of Child Health and Human Development (NICHD); Boston Children’s Hospital Translational Research Program/Innovator Award (B.S.). Conflict of interest: D.A.K. has received research funding from Novartis Pharmaceuticals and has received additional compen- sation for consulting and/or speaking services on behalf of Novartis and Upsher-Smith Pharmaceuticals. He also serves on multiple advisory and service boards of the Tuberous Sclerosis Alliance. J.W. serves on the professional advisory board for the Tuberous Sclerosis Alliance and the editorial board for Pediatric Investigation, has received honoraria from, and serves on the scientific advisory board and the speakers’ bureau for Novartis Pharmaceuticals Inc. and GW Pharmaceutical. M.S. reports grant support from Novartis, Roche, Pfizer, Ipsen, LAM Therapeutics and Quadrant Biosciences. He has served on Scientific Advisory Boards for Sage, Roche, Celgene and Takeda.
Keywords
- autism
- connectivity fingerprint
- fusiform gyrus
- tuberous sclerosis complex
ASJC Scopus subject areas
- Cognitive Neuroscience
- Cellular and Molecular Neuroscience