Effects of Prenatal Exposure to Air Pollution and Early Life Stress on Dopaminergic and Cognitive Systems and Their Contributions to Environmentally-Associated Learning Difficulties

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Learning difficulties (LDiff) are a pervasive, impairing, and costly problem that disproportionately affect children living in economically disadvantaged communities. Youth from disadvantaged communities also experience disproportionate exposure to air pollution and to psychosocial stressors, and we have shown that prenatal exposure to air pollution compounds effects of early life stress (ELS) on cognitive and psychological outcomes in youth. This study will investigate biological and cognitive pathways from prenatal air pollution and stress (ELS) exposure to LDiff. We hypothesize that the neurobiological basis of LDiff among children from economically disadvantaged backgrounds derives from brain system dysfunction related to chemical and social exposures, resulting in unique neural signatures of LDiff in these children. In animal models, prenatal exposure to air pollution and chronic stress alter levels of dopamine and its metabolites across the prefrontal cortex and the dorsal and ventral striatum. These dopaminergic circuits mediate core cognitive processes, such as inhibitory control and reinforcement learning which may be domain general areas of deficit leading to LDiff. Relevant to the proposed work, we have recently shown that lower inhibitory control mediates pollution-related effects on reading and math problems in children from economically disadvantaged families. Such findings suggest that prenatal exposure to air pollution in humans may be linked with LDiff via dopamine-mediated disturbances in inhibitory control and reinforcement learning. The cognitive and neural pathways linking exposure to low achievement, particularly in children from economically disadvantaged backgrounds at high risk of experiencing prenatal exposure to air pollution and early life stress, however, remain understudied. Documenting these pathways will establish this environmentally-associated phenotype of LDiff. Impact: This LD Hub will integrate innovative magnetic resonance of neuromelanin, a metabolite of dopamine, with computational modeling of inhibitory control and reinforcement learning, cognitive processes served by dopamine and that contribute to learning, and granular measures of early life stress. By studying these pathways from exposure to LDiff, we will greatly enhance our ability to comprehensively characterize the complex LDiff faced by children from economically disadvantaged backgrounds. These signatures will serve as targets for the design of intervention programs for adolescents with entrenched LDiff and early intervention programs for young children with emerging problems to be conducted in a future CU Center for Environmental LD Research submission.