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

在子宫内暴露于环境化学物质会干扰动物和人类的神经行为发育 人类。将宫内环境暴露与神经行为发育联系起来的途径可能包括 暴露导致支持认知控制和奖励的神经回路功能的变化 流程。我们假设，这些回路功能的变化可能是 环境暴露和一系列不良适应行为通常出现在儿童后期和 青春期，这一时期在很大程度上没有被充分研究，因为产前暴露对 神经发育结果。这些行为症状包括注意力问题、药物滥用和 精神病的经历。本研究将：1)应用新的模式识别方法来识别特定的 产前化学和社会暴露的复杂高维混合物的暴露情况和 检查这些特征如何解释青春期这些行为症状的风险变化；2)使用任务 以及静息状态功能磁共振成像(FMRI)，以确定不同的暴露配置文件如何影响支持 认知控制和强化学习；以及3)探索暴露是否会导致大脑激活的变化 和连接性在产前暴露情况和行为症状之间的联系 青春期。 影响：R01将整合先进的模式识别方法、认知神经科学方法和 最先进的功能磁共振成像技术探索产前暴露改变以后行为的大脑通路 在青春期。我们将探索大脑功能的基于回路的变化，这些变化可能调解 产前暴露情况和精神障碍的症状，通常出现并共同出现在 青春期。通过同时研究化学和社会应激源的混合物以及共同应激源的概况 一旦出现症状，我们将大大提高对复杂影响的综合表征能力 产前环境暴露对青春期行为症状的影响。我们的发现将允许公众 健康干预改善儿童围产期环境质量和新奇发育 电路专用干预工具。

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.