Mechanisms Conferring Risk versus Resilience for Autism Spectrum Disorder in Early Infancy

Author(s): Tsang, Tawny | Advisor(s): Dapretto, Mirella; Johnson, Scott P | Abstract: Autism spectrum disorder (ASD) is a highly prevalent, lifelong condition characterized by impairments in social communication and the presence of restrictive, repetitive behaviors. Identifying the earliest signs of ASD is a critical factor in promoting optimal long-term outcomes for those affected. The developmental origins of ASD, including symptom onset and progression, remain poorly understood. Current known markers of ASD are centered on deviations in social and communicative skills that typically emerge around the first birthday; however, the presence of overt impairments reflects the consequence of an altered trajectory of social development, rather than the causes and underlying mechanisms from which these impairments arose. This has motivated the search for early risk markers more proximal to the source of deficits, including aberrations in early emerging neural systems that scaffold social development. Prior behavioral research has primarily focused the search within a single developmental domain, but this approach has fallen short of identifying reliable markers of ASD risk within the first 12 months. Instead, infants who develop ASD may exhibit impairments across several developmental domains, including diminished social attention in both visual and auditory domains as well as atypical brain organization in early infancy. This dissertation builds upon these bodies of research to provide a comprehensive profile of ASD risk in early infancy. The studies take a multimodal approach and employ eye-tracking, task-based and resting-state functional neuroimaging, and behavioral measures to investigate developmental antecedents of the social deficits and other core behavioral symptoms associated with ASD across early emerging domains critical for social development. Study 1 used eye-tracking methods to examine visual social attention to faces from 3- to 12-months of age in infants at high- and low-risk for ASD, as well as factors that may moderate developmental trajectories. Greater parental affectedness of ASD-related behaviors predicted slower developmental increases in attention to faces, indicating that parents’ social communicative skills influence their infant’s social development. Moreover, developmental trajectories in face-looking in high-risk infants predicted social communicative functioning. Altogether the findings suggest that parent-mediated interventions targeting parent-child interactions may have positive effects on social communicative development in infants with familial risk for ASD. Study 2 used a passive listening stimulus-evoked functional magnetic resonance imaging (fMRI) paradigm to evaluate native language processing (i.e., auditory social attention) in 1.5 and 9-month-old infants at familial risk for ASD. At 1.5 months, high-risk infants already showed evidence for suboptimal language processing. At 9-months, high-risk infants exhibited attenuated neural responses to language relative to their low-risk peers, and this effect was particularly pronounced in high-risk infants who later displayed delayed language development. Severity of social impairments was higher for high-risk infants with delayed language than those without. Deviations in language processing may constitute an early marker of social communicative difficulties associated with ASD risk. Study 3 combined eye-tracking and resting-state fMRI methods to evaluate Salience Network connectivity at 6 weeks and its association with subsequent social communicative skills and sensory processing abilities. Six-week-old high-risk infants demonstrated hyperconnectivity with sensorimotor regions, whereas low-risk demonstrated hyperconnectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct attentional tradeoff for sensory versus socially-relevant information. Alterations in network connectivity at six weeks predicted 12-month ASD symptomatology, providing the earliest mechanistic account for the unfolding of atypical trajectories associated with ASD risk. Initial disruptions in brain systems involved in sensory/attentional processes are a critical antecedent to the later-emerging social symptoms of ASD. Taken together, the findings from these studies indicate that a multimodal approach that includes early brain-based measures has the incredible potential to improve the early detection of ASD risk as well as uncover mechanisms associated with the emergence of ASD symptomatology within the first few weeks of postnatal life.