The Developing Brain: Influences and Outcomes

发育中的大脑：影响和结果

• 批准号: 10099930
• 负责人: Viren Andrew D'Sa
• 金额: $ 350.84万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10099930
• 关键词: Developing; Brain; Influences; Outcomes

PROJECT SUMMARY / DESCRIPTION How does our healthy brain grow? The simplicity of this question masks the highly complex and multifaceted nature of human neurodevelopment. Across fetal development, infancy and early childhood, our brain undergoes remarkable change in response to diverse genetic and environmental pressures. Processes including myelination and synaptogenesis are at their peak across the first 2-3yrs of life, contributing to the emergence of nearly all cognitive and behavioral skills, and laying the foundation for future learning and academic success. While the importance of this early life period to life-long mental health is widely recognized, important questions remain regarding the influences that shape brain growth and cognitive development: 1. How is brain growth altered by specific pre- and post-natal environmental or genetic factors; 2. How are patterns of brain growth associated with, and predictive of, emerging cognitive and behavioral abilities; and 3. How are these brain-behavior relationships influenced by modifiable factors experienced throughout childhood? This proposal seeks to address these fundamental questions using a unique longitudinal neuroimaging dataset that spans fetal, infant and childhood development (22wks to 10yrs of age) and contains more than 2500 measures from ~650 children with diverse birth outcomes, environmental exposures and genotypes. Alongside multimodal MRI, extensive neurocognitive, sociodemographic, physical health, family and medical history, anthropometric, nutrition, sleep, and biospecimen (DNA, oral and fecal microbiome, and shed deciduous teeth) data have been collected on each child and updated at biannual or annual visits. Using this extensive dataset, we aim to address our central hypothesis: that intrauterine events, early life environmental exposures and genetic factors influence cognitive/behavioral outcomes by altering patterns of brain growth. We will examine this hypothesis in three incremental steps. First, we will demonstrate that intrauterine events, early life exposures and specific genetic polymorphisms give rise to altered trajectories of brain development. Next, we will show that differing patterns of neurodevelopment are associated with varying cognitive and behavioral profiles. Finally, we will take a holistic approach and examine how modifiable factors, specifically child nutrition and obesity, sleep health, and our microbiome may mediate these brain-cognition/behavior relationships within the context of related pre- and post-natal environmental and genetic influences. This marks a distinct departure from prior studies, which have typically examined these factors in relative isolation and using cross-sectional study designs. Over the course of this proposal, an additional 500 children will be recruited and 3000 longitudinal measures acquired (bringing the totals to ~1100 children and ~6100 measures). This represents the largest pediatric neuroimaging database that spans birth to 10yrs, and the only that includes fetal and infant measures on the same children. This study and dataset, therefore, represent an unprecedented opportunity to examine the diverse influences, and their complex interactions, that shape brain growth across a fundamental yet understudied period of development.

项目概要/描述 我们健康的大脑是如何生长的？这个问题的简单性掩盖了它的高度复杂性和多方面性。 人类神经发育的本质在胎儿发育、婴儿期和幼儿期，我们的大脑 在不同的遗传和环境压力下发生了显著的变化。过程 包括髓鞘形成和突触发生在生命的前2- 3年处于高峰，有助于 几乎所有的认知和行为技能的出现，并为未来的学习奠定基础， 学术上的成功虽然这一生命早期对终身心理健康的重要性已被广泛认识， 关于影响大脑发育和认知发展的因素，仍然存在一些重要的问题：1.如何 大脑生长是否因特定的产前和产后环境或遗传因素而改变; 2.如何将模式 与新兴的认知和行为能力相关并预测新兴的认知和行为能力的大脑生长;以及3.好吗 这些大脑行为关系受到整个童年时期经历的可变因素的影响？这 该提案试图使用独特的纵向神经成像数据集来解决这些基本问题， 涵盖胎儿，婴儿和儿童发育（22周龄至10岁），包含2500多项措施 来自约650名具有不同出生结局、环境暴露和基因型的儿童。除了多式联运 MRI、广泛的神经认知、社会人口统计学、身体健康、家族和病史、人体测量， 营养、睡眠和生物样本（DNA、口腔和粪便微生物组以及脱落的乳牙）数据已经被 收集每个孩子的数据，并在半年或一年的访问中更新。利用这一广泛的数据集，我们的目标是 解决我们的中心假设：宫内事件、早期环境暴露和遗传因素 通过改变大脑发育模式来影响认知/行为结果。我们将在 三个渐进步骤。首先，我们将证明宫内事件，早期生活暴露和特定的 遗传多态性导致大脑发育轨迹的改变。接下来，我们将展示不同的 神经发育的模式与不同的认知和行为特征有关。最后，我们将 一个整体的方法，并研究如何改变因素，特别是儿童营养和肥胖，睡眠健康， 我们的微生物组可能在相关的前-和后-环境中介导这些大脑-认知/行为关系。 出生后的环境和遗传影响。这标志着与先前研究的明显偏离， 通常在相对孤立的情况下使用横断面研究设计来检查这些因素。过程中 在这项提议中，将招募另外500名儿童，并获得3000个纵向措施（ 总共约1100名儿童和约6100项措施）。这是世界上最大的儿科神经影像数据库 这是从出生到10岁的唯一一次，也是唯一一次对同一个孩子进行胎儿和婴儿测量。本研究 和数据集，因此，代表了一个前所未有的机会，检查不同的影响， 复杂的相互作用，在一个基本但未被充分研究的发展时期塑造大脑的生长。