Brain Development in Toddlers and Preschoolers with Autism Spectrum Disorder: A Multimodal MRI Examination

Although symptoms of autism spectrum disorder (ASD) emerge in the first years of life, little is known about the trajectories of brain development and their relation to symptom onset in the first years of life in ASD. Identification of early brain markers of ASD during one of the most dynamic and vulnerable neurodevelopmental periods is critical to developing more targeted intervention programs. This three-paper dissertation used anatomical and functional MRI in combination with clinical and behavioral data that have been collected from toddlers and preschoolers with ASD and typically developing (TD) young children in the context of the SDSU Toddler MRI Project. Study 1 (Chen et al., 2021) used resting-state fMRI data acquired during natural sleep from 24 children with early diagnosis of ASD and 33 TD children (aged 1.5-3.5 years) to examine intrinsic functional connectivity (iFC) within and between functional networks generated with independent component analysis. Atypically increased iFC between visual and sensorimotor networks was found in young children with ASD, and was linked with greater autism symptoms, suggesting that disrupted connectivity within primary sensory circuits may be implicated in the emergence of autism symptomatology. Building upon these results, Study 2 (Chen et al., 2022) examined intracortical myelination, an aspect of brain maturation essential for establishing and maintaining neural connectivity, using anatomical T1-weighted and T2-weighted MRI data acquired in 21 young children with ASD and 16 TD children (aged 1.5-5.5 years). Although no group differences were found between TD children and those with ASD in intracortical myelin estimated with T1w/T2w ratio, differential associations between T1w/T2w and age were identified in several early myelinated regions in the ASD and TD groups. The atypical age-related effects in intracortical myelin suggested a disruption in myelination in the first years of life in ASD, which may have cascading effects on brain network connectivity development. Study 3 (Chen et al., in preparation) examined multivariate relationships between brain structure and function using morphometric measures (i.e., surface area and cortical thickness) and an index of local spontaneous activity (fractional Amplitude of Low Frequency Fluctuation) in 38 young children with ASD and 31 TD children (aged 1.5-5.5 years) using canonical correlation analysis. Significantly reduced structure-function correlation and differential age-related effects in structure-function covariation were identified in the ASD cohort as compared to children with typical development. Furthermore, the functional composite capturing local spontaneous activity was associated with overall developmental and adaptive behavior skills in children with ASD. Collectively, Studies 1, 2, and 3 showed that multiple neurodevelopmental processes (i.e., functional network and connectivity, intracortical myelination, cortical morphometry, and local spontaneous activity) are implicated in ASD in early childhood, when autism symptoms first manifest. These findings highlight the importance of integrating multimodal data and examining distinct but complementary anatomical and functional brain measures to elucidate the trajectories of early brain development in ASD