Flattened Structural Network Changes and Association of Hyperconnectivity With Symptom Severity in 2-7-Year-Old Children With Autism

Understanding the brain differences present at the earliest possible diagnostic age for autism spectrum disorder (ASD) is crucial for delineating the underlying neuropathology of the disorder. However, knowledge of brain structural network changes in the early important developmental period between 2 and 7 years of age is limited in children with ASD. In this study, we aimed to fill the knowledge gap by characterizing age-related brain structural network changes in ASD from 2 to 7 years of age, and identify sensitive network-based imaging biomarkers that are significantly correlated with the symptom severity. Diffusion MRI was acquired in 30 children with ASD and 21 typically developmental (TD) children. With diffusion MRI and quantified clinical assessment, we conducted network-based analysis and correlation between graph-theory-based measurements and symptom severity. Significant age-by-group interaction was found in global network measures and nodal efficiencies during the developmental period of 2-7 years old. Compared with significant age-related growth of the structural network in TD, relatively flattened maturational trends were observed in ASD. Hyper-connectivity in the structural network with higher global efficiency, global network strength, and nodal efficiency were observed in children with ASD. Network edge strength in ASD also demonstrated hyper-connectivity in widespread anatomical connections, including those in default-mode, frontoparietal, and sensorimotor networks. Importantly, identified higher nodal efficiencies and higher network edge strengths were significantly correlated with symptom severity in ASD. Collectively, structural networks in ASD during this early developmental period of 2-7 years of age are characterized by hyper-connectivity and slower maturation, with aberrant hyper-connectivity significantly correlated with symptom severity. These aberrant network measures may serve as imaging biomarkers for ASD from 2 to 7 years of age.