The Developing Brain: Influences and Outcomes

发育中的大脑：影响和结果

基本信息

批准号：
10019615
负责人：
Viren Andrew D'Sa
金额：
$ 395.08万
依托单位：
RHODE ISLAND HOSPITAL
依托单位国家：
美国
项目类别：
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/10019615
关键词：
Address Adolescent Adult Affect Age Behavior Behavior Disorders Behavioral Birth Body Composition Brain Brain imaging Caring Child Child Nutrition Childhood Clinical Cognition Cognition Disorders Cognitive Collection Complex Conceptions Cross-Sectional Studies DNA Data Data Set Databases Development Disease Elements Environment Environmental Exposure Environmental Risk Factor Event Exposure to Family history of Fetal Development Fetal Growth Retardation Foundations Future Genetic Genetic Polymorphism Genotype Growth Growth Factor Growth and Development function Health Heterogeneity Human Characteristics Image Individual Infant Intervention Learning Life Link Longitudinal Studies Magnetic Resonance Imaging Maps Masks Measurement Measures Mediating Mental Health Mental disorders Modeling Neurocognitive Neurodegenerative Disorders Neurologic Nutritional Outcome Pattern Police Population Premature Birth Process Public Health Research Design Shapes Sleep Statistical Methods Statistical Models Structure Symptoms Techniques Update Variant Visit base behavioral outcome brain behavior brain shape cognitive development cognitive skill cohort deciduous tooth early childhood early life exposure experience fecal microbiome fetal genetic risk factor gut microbiome holistic approach improved in utero infancy insight lead exposure longitudinal analysis microbiome model development multimodality myelination neural network neurobehavioral neurodevelopment neuroimaging nutrition obesity in children oral microbiome physical conditioning postnatal pressure recruit response serial imaging skills sleep health sociodemographics success synaptic pruning synaptogenesis

项目摘要

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如何成长？这个问题的简单性掩盖了高度复杂和多方面的问题人类神经发育的本质。在胎儿发育、婴儿期和幼儿期，我们的大脑为了应对不同的遗传和环境压力而发生显着的变化。流程包括髓鞘形成和突触发生在生命的前 2-3 年达到顶峰，有助于几乎所有认知和行为技能的出现，为未来的学习和学业上的成功。尽管人们普遍认识到生命早期阶段对终生心理健康的重要性，关于影响大脑生长和认知发展的重要问题仍然存在： 1. 如何影响大脑发育和认知发展？特定的产前和产后环境或遗传因素是否改变了大脑的生长？ 2. 模式如何大脑发育与新兴认知和行为能力相关并可预测； 3. 怎么样？这些大脑行为关系是否受到整个童年经历的可改变因素的影响？这该提案旨在使用独特的纵向神经影像数据集来解决这些基本问题，该数据集涵盖胎儿、婴儿和儿童发育（22 周至 10 岁），包含 2500 多个措施来自约 650 名具有不同出生结果、环境暴露和基因型的儿童。与多式联运并驾齐驱 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）数据已收集每个孩子的信息，并在每两年或每年一次的访问中进行更新。使用这个广泛的数据集，我们的目标是解决我们的中心假设：宫内事件、早期生命环境暴露和遗传因素通过改变大脑生长模式来影响认知/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、早期生命暴露和特定的遗传多态性会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模式与不同的认知和行为特征相关。最后，我们将采取采取整体方法，研究可改变的因素，特别是儿童营养和肥胖、睡眠健康和我们的微生物组可能会在相关的前和后的背景下介导这些大脑认知/行为关系产后环境和遗传的影响。这标志着与先前研究的明显背离，先前的研究通常使用横断面研究设计相对孤立地检查这些因素。在课程中根据该提案，将另外招募 500 名儿童，并获得 3000 项纵向措施（使总数约 1100 名儿童和约 6100 项措施）。这是最大的儿科神经影像数据库该项目涵盖出生至 10 岁，也是唯一一项包括对同一儿童进行胎儿和婴儿测量的项目。这项研究因此，数据集代表了一个前所未有的机会来检查不同的影响及其影响复杂的相互作用，在一个基本但尚未得到充分研究的发展时期塑造大脑的生长。