Autism spectrum disorders (ASD) are highly prevalent, lifelong conditions 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 symptom-based markers of ASD are based 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 biomarkers more proximal to the source of deficits, including aberrations in early emerging neural systems that scaffold social development. Prior biomarker research has primarily focused the search within a single developmental domain, but this approach has fallen short of identifying a reliable risk marker of ASD within the first 12 months. Instead, infants who develop ASD may exhibit impairment across several developmental domains, including diminished social attention in both visual and auditory domains and atypical brain organization in early infancy. Furthermore, infant sibling research has not previously leveraged existing knowledge about autism-susceptibility genes?such as CNTNAP2, a gene strongly involved in the development of frontal-striatal networks integral for social cognition and communication?to examine relations between genetic variation and ASD-related phenotypes. The current proposal builds upon these bodies of research to provide a comprehensive profile of ASD risk in early infancy. The proposed studies will employ eye-tracking, neuroimaging, and neurobehavioral genetics to investigate developmental antecedents of the social and restrictive behavioral symptoms associated with ASD across early emerging domains critical for social development. Specifically, the studies will evaluate developmental trajectories in visual attention to faces from 3- to 12-months (Aim 1), the neural correlates of native language processing at 1.5 months (Aim 2), and early functional brain connectivity within the Salience Network at 1.5 months (Aim 3). Individual differences within each of these domains may index an infant's capacity to attend to, and learn from, socially relevant information in their immediate environments.
Aim 4 examines whether early deviations in visual social attention to faces, early native language processing (as indexed by fMRI), and altered functional brain connectivity are affected by CNTNAP2 genotype. Taken together, the multimodal approach in the proposed studies will enhance our ability to detect infants most vulnerable for atypical social development and further our understanding of the developmental pathogenesis of ASD.

Public Health Relevance

A better understanding of the early developmental antecedents to the overt behavioral symptoms of autism spectrum disorders (ASD) is necessary to advance the early detection and treatment for ASD. This project will examine functioning across early-developing neural systems in infants at high and low risk for ASD in order to identify reliable markers of aberrant social development within the first 12 months. This endeavor will contribute to the refinement of screening tools and the development of targeted intervention strategies that will ultimately improve the outcomes of affected individuals and reduce the substantial familial and societal costs associated with ASD across the lifespan.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31HD090937-01A1
Application #
9328900
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kau, Alice S
Project Start
2017-09-01
Project End
2018-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Tsang, Tawny; Atagi, Natsuki; Johnson, Scott P (2018) Selective attention to the mouth is associated with expressive language skills in monolingual and bilingual infants. J Exp Child Psychol 169:93-109