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

学习困难（LDiff）是一个普遍的，有害的，代价高昂的问题，不成比例地影响儿童 生活在经济上处于不利地位的社区。来自弱势社区的青年也会经历 不成比例地暴露于空气污染和心理压力，我们已经表明，产前 暴露于空气污染化合物对早期生活压力（ELS）的认知和心理结果的影响 在年轻的时候。这项研究将探讨产前空气污染和压力的生物和认知途径 (ELS)暴露于LDiff。 我们假设，在经济困难的儿童中，LDiff的神经生物学基础 背景来源于与化学和社会接触有关的脑系统功能障碍， LDiff的独特神经信号在动物模型中，产前暴露于空气污染和 慢性压力会改变前额叶皮层和背侧皮层的多巴胺及其代谢物的水平， 腹侧纹状体这些多巴胺能回路介导核心认知过程，如抑制控制和 强化学习可能是导致LDiff的领域一般缺陷。与拟议的 工作，我们最近表明，较低的抑制控制介导污染相关的影响阅读和 贫困家庭孩子的数学问题。这些发现表明，产前 暴露于空气污染的人类可能与LDiff通过多巴胺介导的干扰抑制 控制和强化学习。认知和神经通路将暴露与低成就联系起来， 特别是来自经济上处于不利地位背景的儿童， 然而，暴露于空气污染和早期生活压力仍然没有得到充分的研究。记录这些途径将 建立这种与环境相关的LDiff表型。影响：这个LD中心将整合创新的 神经黑色素的磁共振，多巴胺的代谢物，与计算建模， 抑制控制和强化学习，由多巴胺服务的认知过程， 有助于学习，以及早期生活压力的粒度测量。通过研究这些途径， 接触LDiff，我们将大大提高我们全面表征复杂的能力， 来自经济弱势背景的儿童面临的LDiff问题。这些签名将作为 为患有根深蒂固的LDiff和早期LDiff的青少年设计干预方案的目标 为有新问题的幼儿而设的辅导计划，将于未来的幼儿中心推行 环境LD研究中心提交。

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.