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哺乳动物的神经行为发育。 人类将子宫内环境暴露与神经行为发育联系起来的途径可能包括 应激诱导的支持认知控制和奖励的神经回路功能变化 流程.我们假设这些回路功能的变化可能是 环境暴露和一系列适应不良的行为，通常出现在童年后期， 青春期，这一时期在产前暴露对儿童的影响方面研究得很不够。 神经发育结果。这些行为症状包括注意力问题，药物滥用， 精神病经历本研究将：1）应用新的模式识别方法来识别特定的 产前化学品和社会接触的复杂高维混合物的接触概况， 研究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 和静息状态功能性磁共振成像（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）探索是否有应激诱导的大脑激活变化 和连接性介导产前暴露概况和行为症状之间的关联， 青春期 影响：R 01将整合先进的模式识别方法，认知神经科学方法， 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。我们将探讨大脑功能中基于回路的变化，这些变化可能介导 产前暴露概况和精神疾病的症状，通常出现和共同发生在 青春期通过同时研究化学和社会压力源的混合物以及协同作用的概况， 出现的症状，我们将大大提高我们的能力，全面描述复杂的影响， 产前环境暴露对青春期行为症状的影响。我们的发现将使公众 卫生干预措施，以改善儿童的围产期环境的质量和新的发展， 电路特定干预工具。

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.