Neural Connectivity in Infants at Familial Risk for Autism Spectrum Disorder
While autism spectrum disorder (ASD) is diagnosed based on behavioral symptoms at 3 years of age, the infant sibling study design has enabled the detection and characterization of atypical neural development during the first year of life, prior to the emergence of behavioral symptoms. Infants who have older siblings with ASD are at increased risk for ASD, language delay, and other neurodevelopmental delays. As such, it is important to identify as early as possible if an infant is on a trajectory towards atypical development in order to help guide close monitoring and implement targeted behavioral interventions. The body of work in this dissertation contributes to the field of infant sibling research by showing that with robust methods, electroencephalography (EEG) can be used to detect altered functional connectivity during the first year of life, starting as early as 3 months of age. Chapter 1 introduces known deficits in behaviors and neural connectivity in infants at risk for ASD, highlights methodological gaps in the field of EEG infant research, and outlines the goals of this dissertation. Chapter 2 addresses methodological considerations in the development of an EEG pre-processing pipeline, designed to maximize data quality and data retention for infant EEG. Chapters 3 through 5 present different aspects of a comprehensive study of functional connectivity during language processing in infants at risk for ASD, with focus on theta (4-6 Hz) and alpha (6-12 Hz) spectral power and phase coherence within putative language networks. Chapter 3 describes differences in coherence at 3-months of age in infants who show ASD symptoms at 18-months of age. Chapter 4 highlights altered trajectories in coherence development over the first year of life in infants who later have ASD symptoms at 18-months. At the same left fronto-central network that differentiated risk groups at 3-months of age, reduced average coherence over the first year of life is maintained in infants who showed ASD symptoms at 18 months. Chapter 5 characterizes connectivity as an endophenotype of ASD in familial risk infants using both the 3-month cross-sectional study design and the 3-12-month longitudinal study design. Connectivity measures that differentiate risk groups in Chapters 3-5 also relate to language ability and ASD symptoms at 18-months of age. Taken together, the body of work in this dissertation support the hypothesis that early differences in neural connectivity lay a foundation for and precede behavioral signs of neurodevelopmental disabilities in infants at risk for ASD.