Doctor of Philosophy

dissertationAutism spectrum disorder is a heterogeneous neurodevelopmental disorder characterized by social/communicative deficits and restricted interests/repetitive behaviors. The intrinsic heterogeneity of individuals along the autism spectrum complicates research efforts attempting to elucidate the neural correlates related to the diagnosis. Functional neuroimaging may be best suited to address this problem as it offers a dynamic perspective of brain activation patterns as they adapt along with behavior throughout development. Resting-state functional connectivity has identified dysfunction in large-scale functional networks in autism. However, the exact nature of the network dysfunction remains obscure. In Chapter 2, a new method is proposed for investigating the temporal component of functional connectivity that we have termed sustained connectivity. Results from this study found that sustained connectivity is a reproducible trait in individuals, is heritable, more transient in females, shows changes with age in early adulthood, and is strongly associated with individual differences in processing speed, particularly in men. In Chapter 3, using this new method, we describe widespread increases in sustained connectivity and further lag-based findings in individuals with autism compared to controls. Additionally, a positive correlation was found between measures of symptom severity and sustained connectivity values in individuals with autism. Lastly, in Chapter 4, several functional connectivity methods used to investigate aberrant connectivity patterns in autism are compared in a large iv publicly available dataset comprised of data from multiple research sites and a high temporal resolution replication sample. No single method of analysis provided reproducible findings across multiple research sites, the combined dataset, or the highresolution dataset. Features selected across methods revealed similarities in their relationship to behavioral traits common with autism. However, lag-based functional connectivity, an analogue to sustained connectivity, was distinct from the other methods in describing patterns of resting-state functional connectivity and its relationship to autism traits. Together, these results suggest that neuroimaging research into the pathophysiology of autism will benefit from further development of functional connectivity analysis methods. Such methods should describe more nuanced components of brain activity, including the temporal domain, and be more sensitive to individual differences in autism