Abstract
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.
Highlights
Autism spectrum disorder (ASD) is characterized by deficits in social communication and interactions, repetitive patterns of behaviors, and restricted interests (Constantino and Charman, 2016)
We aimed to characterize age-related brain structural network changes in young children with autism spectrum disorder (ASD) from 2 to 7 years of age, and to identify sensitive network-based imaging biomarkers that are significantly correlated with the symptom severity during this early developmental period
There was no significant difference in median age between ASD and typically developmental (TD) (Wilcoxon ranksum test, p = 0.8)
Summary
Autism spectrum disorder (ASD) is characterized by deficits in social communication and interactions, repetitive patterns of behaviors, and restricted interests (Constantino and Charman, 2016). The age range of 2–7 years is a critical developmental period for understanding ASD as it is a time frame immediately after the earliest possible ASD diagnosis around 2–3 years of age based on current clinical diagnostic methods (Ozonoff et al, 2010). Diffusion MRI studies on the important early developmental period of 2–7 years in ASD are relatively scarce and were conducted to investigate white matter microstructural changes (e.g., Ben Bashat et al, 2007; Walker et al, 2012; Ouyang et al, 2016). Since ASD has numerous implications for patient function and integration in society, early interventions for ASD immediately after its diagnosis at around 2 years of age are more likely to reduce symptoms and to positively affect long-term neurodevelopment (Zwaigenbaum et al, 2015). Current lack of understanding about ASD in the age range of 2–7 years limits potential approaches for early intervention
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