Prenatal Environmental Mixtures, Cognitive Control and Reward Processes, And Risk for Psychiatric Problems in Adolescence.

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In utero exposure to environmental chemicals can disturb neurobehavioral development in both animals and in humans. The pathways linking in utero environmental exposures to neurobehavioral development likely involve exposure-induced changes in the function of neural circuits that support cognitive control and reward processes. We hypothesize that changes in the function of these circuits may act as a pathway between environmental exposure and a range of maladaptive behaviors that commonly emerge in late childhood and adolescence, a period that has been largely understudied with respect to the effects of prenatal exposures on neurodevelopmental outcomes. Such behavioral symptoms include attention problems, substance abuse, and psychotic experiences. This study will: 1) apply novel pattern recognition approaches to identify specific exposure profiles of complex high-dimensional mixtures of prenatal chemical and social exposures and examine how these profiles explain variation in risk for these behavioral symptoms in adolescence; 2) use task and resting state functional MRI (fMRI) to identify how distinct exposure profiles affect circuits that support cognitive control and reinforcement learning; and 3) explore if exposure-induced changes in brain activation and connectivity mediate associations between prenatal exposure profiles and behavioral symptoms in adolescence. Impact: This R01 will integrate advanced pattern recognition methods, a cognitive neuroscience approach and state-of-the-art fMRI techniques to explore brain pathways through which prenatal exposures alter behavior later in adolescence. We will explore circuit-based changes in brain function that may mediate associations between prenatal exposure profiles and symptoms of psychiatric disorders that typically emerge and co-occur in adolescence. By simultaneously studying mixtures of chemical and social stressors as well as profiles of co- occurring symptoms, we will greatly enhance our ability to comprehensively characterize the complex impacts of prenatal environmental exposures on behavioral symptoms in adolescence. Our findings will allow public health interventions to improve the quality of children's perinatal environment and the development of novel circuit-specific intervention tools.