Jason J. Wolff, Ph.D. - US grants

DESCRIPTION (provided by applicant): This proposed Mentored Research Scientist CDA (K01) seeks support to foster an independent research career bridging the study of brain development in children with autism spectrum disorder (ASD) to that of early intervention. The developing brain is highly malleable, and interventions which capitalize on this quality hold great promise. However, response to intervention is variable and dependent on individual differences, an issue compounded by ASD heterogeneity. Linking traditionally separate lines of intervention and neurobehavioral research has the potential to aid efforts to optimally individualize intervention. In the short term, the candidate's career goals include identifying early brain-behavior markers of behavioral outcomes and treatment response. In the longer term, the candidate plans to leverage this information to develop targeted early interventions. The candidate is trained in special education, behavior analysis, and developmental neuroscience. To achieve the goal of developing neurobehaviorally informed interventions, the candidate will engage in new and comprehensive training in intervention science with a focus on early intervention for autism, new training in structural brain imaging analysis, and additional statistical and methodological training. Activities supporting these content areas include hands-on training, coursework, journal clubs and directed readings, specialty conference and institute participation, and professional development seminars, with training culminating in the preparation of an R01 grant. The candidate will also investigate brain imaging predictors of: 1) joint attention in toddlers with ASD and 2) response to intervention for joint attention. In the fist study, the candidate will examine concurrent and predictive imaging markers of joint attention in an existing longitudinal sample of toddlers with ASD. In the second study, the candidate will collect pre-treatment imaging data on ~45 toddlers with ASD enrolled in a funded RCT for joint attention intervention to indentify neural mediators of dimensional outcomes, and conduct an exploratory analysis of differences between high- and low-responders. The University of North Carolina is an active center of autism research. Primary mentor Dr. Joseph Piven is a leading expert in the neurobiology of ASD and has extensive experience mentoring junior scientists. He is Director of the Carolina Institute for Developmental Disabilities (CIDD) and PI of the ACE Network Infant Brain Imaging Study. Co-mentor Dr. Samuel Odom is an accomplished expert in early intervention for ASD. He is Director of the Frank Porter Graham Child Development Institute and PI of many early intervention studies. UNC is home to world-class imaging facilities and experts, including co-mentor Dr. Martin Styner, an expert in structural image analysis and Co-Director of both the Neuro Image Research and Analysis Lab and the CIDD's Developmental Neuroimaging Core. Together, this mentor team is superbly qualified to provide the candidate with training, guidance, and oversight in development activities bridging brain, behavior, and intervention.

Project Summary Restricted and repetitive behaviors (RRB), which under the DSM 5 now include unusual responses to sensory stimuli, are defining features of autism spectrum disorder (ASD) that impede upon adaptive opportunities and play a significant role in lowering quality of life for affected individuals and their families. Despite long standing acknowledgement of these impacts, the neurodevelopmental mechanisms underlying subtypes of RRB are poorly understood, and effective intervention and prevention strategies are severely limited. The long term goal for this project is to utilize developmental behavioral and neuroimaging data to develop risk markers and novel early individualized intervention and strategic prevention strategies targeted to the domain of restricted and repetitive behaviors. The primary objective of the present application is to characterize the neurodevelopmental and behavioral mechanisms underlying specific subtypes and profiles of RRB in a prospectively ascertained sample of children with and without ASD. We will accomplish this objective through partnership with the NIH Autism Center of Excellence Network Infant Brain Imaging Study (IBIS), an ongoing prospective, longitudinal brain imaging study of children with and without autism from infancy through school age. Our central hypothesis is that distinct, biologically informative RRB subtypes will be identified at school-age, and that these subtypes will have emerged through, and be presaged by, a dynamic developmental process beginning in infancy. Identifying behavioral and neurodevelopmental precursors of restricted and repetitive behaviors will provide new and necessary footholds for the creation of early detection and mechanism-based prevention/intervention strategies. The objectives of this application will be addressed through three specific aims: 1) characterize fine-grained dimensions and profiles of RRB in relation to brain development from infancy through school-age; 2) empirically derive infant/toddler age risk markers for later RRB; and 3) explore the relations between RRB and the home and school environments. Existing longitudinal brain imaging and behavioral data collected through IBIS will be integrated with new measures specifically designed by our team to capture dimensions of restricted and repetitive behavior (including direct quantitative measures of sensory responsivity), as well as rich information pertaining to the environments in which these behaviors occur. This work is innovative in that it offers an unprecedented opportunity to comprehensively chart the behavioral and neurodevelopmental mechanisms underlying specific RRB subtypes and identify early-emerging markers of later outcomes. Results from this project will inform: 1) the pathogenesis of subtypes of RRB, 2) their relations to each other and to the external environment, and 3) set the stage for the development of early screening and targeted prevention/intervention procedures.