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

产前空气污染暴露和早期生活压力对多巴胺能和认知系统的影响及其对环境相关学习困难的影响

• 批准号: 10533148
• 负责人: AMY MARGOLIS
• 金额: $ 30.53万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10533148
• 关键词: Academic achievement; Academic support; Achievement; Adolescent; Affect; Age; Air Pollutants; Air Pollution; Animal Model; Area; Aromatic Polycyclic Hydrocarbons; Behavior; Behavioral; Biological; Birth; Black race; Brain; Budgets; Categories; Chemicals; Child; Childhood; Chronic stress; Cognitive; Communities; Complex; Computer Models; Corpus striatum structure; Data; Data Collection; Development; Diffusion; Dimensions; Disadvantaged; Dopamine; Dorsal; Early Intervention; Economically Deprived Population; Environmental Health; Exposure to; Family; Functional disorder; Future; Human; Impairment; Instruction; Interdisciplinary Education; Intervention; Latinx; Learning; Learning Disabilities; Link; Magnetic Resonance; Magnetic Resonance Imaging; Mathematics; Measurement; Measures; Mediating; Methods; Midbrain structure; Neural Pathways; Neurobiology; Participant; Pathway interactions; Pattern; Performance; Phenotype; Pollution; Polycyclic Compounds; Prefrontal Cortex; Proxy; Psychiatry; Psychological reinforcement; Psychology; Public Health; Reading; Research; Research Project Grants; Sampling; Science; Socioeconomic Status; Standardization; Stress; Substantia nigra structure; System; Testing; Third Pregnancy Trimester; Time; Ventral Striatum; Ventral Tegmental Area; Work; Youth; air monitoring; classical conditioning; cognitive process; cognitive system; cohort; cost; data infrastructure; disadvantaged background; early experience; early life stress; experience; exposure pathway; federal poverty level; high risk; imaging approach; imaging study; improved; in vivo; information processing; innovation; intervention program; learning outcome; literacy; mathematical ability; neuroimaging; neuromelanin; neuroregulation; neurotoxic; novel; prenatal; prenatal experience; prenatal exposure; prenatal testing; preventive intervention; prospective; psychological outcomes; psychosocial; psychosocial stressors; rapid growth; relating to nervous system; social; therapy design

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.

学习困难(LDiff)是一个普遍、损害和代价高昂的问题，对儿童的影响不成比例 生活在经济困难的社区。来自弱势社区的年轻人也经历了 不成比例地暴露在空气污染和心理社会应激源中，我们已经证明 接触空气污染复合早期生活压力(ELS)对认知和心理结果的影响 在年轻的时候。这项研究将调查来自产前空气污染和压力的生物和认知途径。 (ELS)接触LDiff。 我们假设，来自经济困难儿童的LDiff的神经生物学基础 背景源于与化学和社会接触有关的大脑系统功能障碍，导致 LDiff在这些孩子身上的独特神经特征。在动物模型中，产前暴露于空气污染和 慢性应激改变了前额叶皮质、背侧和背侧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的领域普遍缺陷。与建议的 我们最近的研究表明，较低的抑制性控制会对阅读和阅读产生与污染相关的影响 来自经济困难家庭的孩子的数学问题。这些发现表明，产前 人类暴露在空气污染中可能通过多巴胺介导的抑制功能紊乱与LDiff有关 控制和强化学习。认知和神经通路将暴露于低成就联系起来， 特别是来自经济困难背景、产前风险较高的儿童 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。记录这些途径将会 建立这种与环境相关的LDiff表型。影响：该LD中心将整合创新 多巴胺的代谢物--神经黑色素的磁共振研究 抑制性控制和强化学习，多巴胺等的认知过程 有助于学习，并对早期生活压力进行细粒度测量。通过从以下方面研究这些途径 暴露在LDiff下，我们将极大地增强我们全面表征络合物的能力 来自经济困难背景的儿童面临的LDiff。这些签名将用作 根深蒂固的LDiff和早期青少年干预方案设计的目标 针对新出现问题的幼儿的干预计划将在未来的CU进行 环境LD研究中心提交。