ADVANCING EARLY BEHAVIORAL AND NEURAL PHENOTYPES OF SOCIAL MOTIVATION IN ASD

项目总结/文摘

PROJECT SUMMARY/ABSTRACT Autism Spectrum Disorders (ASDs) are increasingly prevalent neurodevelopmental conditions characterized by core deficits in social communication and significant impairments in daily living skills, with the cost of support for ASD-affected individuals estimated at over eleven billion dollars per year in the United States. There is no cure for ASD, and although early interventions prior to age 3 can improve outcomes, the median age of diagnosis in the U.S. is still close to 4 years. The elucidation of developmental mechanisms of ASD will be critical for 1) advancing the age of earliest diagnosis and 2) optimizing current therapeutic targets. One under-explored theory of ASD proposes that early deficiencies in social motivation, the human drive to orient preferentially to social stimuli and to seek and maintain social interactions, prevent children from engaging in social learning experiences, resulting in a cascade of autistic symptoms, including impaired communication. Currently, there is no measure to quantify social motivation in early life, and such a tool is a necessary step to begin to determine how primary deficiencies in social motivation influence the course of ASD, both at the level of behavior and the brain. The research plan for this mentored K08 award proposes to refine an initial social motivation index, derived from existing infant and toddler data from two NIH-funded studies into a heritable, questionnaire-based index that a) is more predictive of ASD and b) can track the course of social motivation in infancy, before ASD is currently diagnosed. This index will then be 1) tested in combination with novel task-based assessments of social motivation, to determine if these direct measures improve the ability to distinguish children with and without ASD, and 2) analyzed in relationship to existing infant neuroimaging data to determine how social motivation relates to structural and functional brain connectivity in early development. To achieve these research objectives, the candidate, a child psychiatrist and neuroscientist, has assembled a multidisciplinary mentoring team who will provide necessary training over a period of 5 years in behavioral phenotyping, statistical modeling, developmental psychology, and processing and analysis of diffusion weighted imaging data (DTI) and resting state functional connectivity magnetic resonance imaging data (rs-fcMRI). The goal of this career development award is to enable the candidate to develop an R01-funded research program aimed at clarifying the relationships between developmental deviations in core social functions, communication, and the neural systems underlying ASD, all of which are important avenues to guide novel targets for intervention. Further, in her future R01 project, the candidate will propose to adapt assessments of social motivation generated through this K08 to younger infants, for whom it could serve as an early diagnostic tool for ASD. This project will thus contribute to advances in early identification and intervention strategies for this often devastating disorder during a more plastic period of child development, thereby promoting significant improvement in quality of life for those affected with ASD.