The Developing Brain: Influences and Outcomes

项目摘要/说明 我们健康的大脑是如何生长的？这个问题的简单性掩盖了高度复杂和多方面的 人类神经发育的本质。在胎儿发育、婴儿期和童年早期，我们的大脑 在应对不同的遗传和环境压力时，经历了显著的变化。流程 包括髓鞘形成和突触形成，在生命的头2-3年处于顶峰，有助于 几乎所有认知和行为技能的出现，并为未来的学习和 学业上的成功。虽然这一早期生命阶段对终生心理健康的重要性得到了广泛的认可， 关于塑造大脑生长和认知发展的影响，重要的问题仍然存在：1.如何 大脑发育是否受到特定的出生前和出生后的环境或遗传因素的影响；2.大脑发育的模式是如何 大脑发育与新出现的认知和行为能力相关并对其进行预测；以及3.如何 这些受可调整因素影响的大脑-行为关系经历了整个童年吗？这 该提案寻求使用一种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、婴儿和儿童的发育(22周至10岁)，包含2500多项指标 来自不同出生结果、环境暴露和基因类型的约650名儿童。与多式联运并存 核磁共振，广泛的神经认知，社会人口学，身体健康，家族和病史，人体测量学， 营养、睡眠和生物量(DNA、口腔和粪便微生物组，以及脱落的乳牙)的数据 收集每个儿童的资料，并在一年两次或每年一次的访问中更新。使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、早期生活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。我们将在以下文件中检验这一假设 三个渐进的步骤。首先，我们将演示宫内事件、早期生命暴露和特定的 基因多态会引起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，我们将带着 一种全面的方法，并检查可修改的因素，特别是儿童营养和肥胖、睡眠健康和 我们的微生物群可能在相关的前和前环境中调节这些大脑-认知/行为关系 产后环境和遗传影响。这标志着与之前的研究截然不同，之前的研究 通常在相对孤立的情况下使用横断面研究设计检查这些因素。在整个过程中 在这项提议中，将额外招募500名儿童，并获得3000项纵向措施(带来 总计约1100名儿童和约6100项措施)。这是最大的儿科神经影像数据库 这包括从出生到10岁，唯一包括对同一个孩子进行胎儿和婴儿测量的婴儿。本研究 因此，数据集代表了一个前所未有的机会来检查各种影响，以及它们的 复杂的相互作用，塑造了大脑在一个基本但未被充分研究的发展时期的生长。

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.