Project Summary Candidate: This application is for a K23 career development award for Nicole McDonald, PhD, an F32 postdoctoral fellow at the University of California, Los Angeles (transitioning to assistant professor by award start date). Dr. McDonald’s career goal is to become an independent investigator of atypical social development in order to inform efforts to identify and treat at-risk infants. This K23 award will provide Dr. McDonald with the necessary training and mentored experience to gain expertise in: 1) advanced developmental neuroscience and electrophysiological (EEG) methods of measuring infant brain development; 2) the effects of early medical risk on brain development and social behavior in neonatal intensive care unit (NICU) graduates; 3) statistical methods for modeling longitudinal data. Environment: Mentorship will be provided by Drs. Shafali Jeste, Isabell Purdy, and Damla Senturk, experts in EEG methods and brain development in neurodevelopmental disorders, high-risk NICU graduates, and statistical models for complex biomedical data, respectively. Research and Career Development: From the first days of life, brain development occurs in the context of everyday interactions between infants and caregivers. Differences in infant brain function may both precede and follow disruptions in early social interactions, precipitating risk for adverse social outcomes while also offering an opportunity to intervene and improve development. Infants who require extended Neonatal Intensive Care Unit (NICU) hospitalizations carry multiple interacting risk factors that increase the likelihood of social deficits, including biological, environmental, and socioeconomic risks. This study will build on the literature on infants with familial risk for autism (i.e., younger siblings of children with autism), which has identified a growing divergence in social communication behavior and brain development between 6 and 12 months of age. Through a collaboration between the UCLA High Risk Infant Follow-Up Clinic and Center for Autism Research and Treatment, this study will examine trajectories of social behavior and brain development from 6 to 12 months in high-risk NICU graduates, infants with familial risk for autism, and low-risk controls. Well-validated measures of social behavior and EEG, an accessible and scalable method of measuring brain function and connectivity during infancy, will be utilized to compare developmental trajectories and examine whether early differences predict variation in social functioning and development at 24 months. It is our eventual goal to apply the identified behavioral and brain markers to a targeted study of an intervention designed to optimize social development in high-risk NICU graduates. These aims directly address NICHD research priorities; in particular, “research on biomarkers and outcome measures for intellectual and developmental disability symptoms, severity assessments, and treatments, especially outcomes targeting cognitive, behavioral, social, and medical issues.”

Project Narrative Infants who experience early medical problems, such as preterm birth, that require an extended Neonatal Intensive Care Unit (NICU) hospitalization are at increased risk for adverse neurodevelopmental outcomes, including social communication deficits, autism, and developmental delays. The proposed study will longitudinally examine trajectories of early brain development and social behavior as predictors of later variation in social and developmental skills in high-risk NICU graduates compared to infants with familial risk and low risk for autism. Results from this study will increase our understanding of developmental risk factors that generalize across risk groups, while also informing efforts to develop treatment approaches that are targeted to the unique biological pathways and behavioral sequelae of early medical risk.