Mapping lifespan trajectories of white matter in autism and improving reproducibility through shared diffusion MRI data - Abstract Autism spectrum disorder (ASD) affects many aspects of development (e.g., social, cognitive) throughout life, and altered neurodevelopment in early life is considered an important feature of ASD pathophysiology. There is, however, considerable uncertainty regarding the neuromaturational trajectory of ASD beyond early childhood—into the transitional periods of adolescence and aging. White matter is necessary for the development of specialized brain circuits. White matter tracts follow a protracted developmental trajectory, peaking in the third to fourth decades of life, and, critically, their maturation may be differentially altered in ASD. Diffusion MRI (dMRI) is currently the most effective non-invasive technique for probing white matter in vivo. Studies of white matter using dMRI in ASD in later childhood to adulthood, however, have provided inconsistent findings. A major hindrance to reproducible white matter results in ASD is low statistical power. Over the last decade, extensive shared multimodal ASD datasets have been made available through large initiatives such as the Autism Brain Imaging Data Exchange, and National Database for Autism Research. The dMRI data from these resources, however, are currently underutilized. In addition, large consortia studies (e.g., the Human Connectome Project) have made high-quality dMRI data available in healthy individuals across the lifespan. Recent methodological advances in data harmonization of dMRI data allow mitigating differences across imaging sites and protocols. This project aims to leverage available multi-site dMRI data (>2600 participants; >600 ASD, >2000 TD; from up to 17 sites) to perform joint large-scale analyses that will elucidate the spatiotemporal pattern of white matter atypicalities in ASD across the lifespan (age 2-70 years). We propose to i) Aggregate, process, and quality control dMRI datasets of individuals with ASD and TD controls from shared databases, and ii) Examine cross- sectional lifespan age trajectories of microstructural measures of white matter tracts at the group level, and multivariate patterns of white matter microstructure at the individual level (using deep normative modeling), in ASD relative to TD controls, and link atypicality of white matter patterns with ASD symptoms. Exploratory analyses on the effects of sex and cognitive abilities will also be performed. This research may aid treatment and policy development by identifying the location and timing of vulnerable neural pathways and circuits in ASD, and, additionally, promote reproducible diffusion MRI research.
