In utero Assessment of the Human Neural Connectome and Later Child Behavior

项目总结 人类胎儿的大脑是复杂的、高度可塑性的，并且极其脆弱。子宫轻度变异可以 严重损害终身学习和神经健康。尽管人们越来越认识到 这一时期出现了许多发育、精神和神经障碍，大范围功能 胎儿大脑的组织结构仍然是神经科学研究的“黑匣子”。虽然有现象级的 检查胎儿大脑解剖的技术，直到最近我们才拥有了非侵入性手段 研究活体人胎脑的协调功能。本项目的重点是了解 从胎儿时期开始的全脑功能回路的出现，并识别之间的关系 产前大脑连接和学龄前儿童实现关键发展里程碑。考虑到 子宫是胎儿的第一环境，因此是生物和环境第一次互动的地方， 我们还将研究产前应激暴露对人类胎儿大脑功能连接的影响。六十 女性将在怀孕25-32周被招募，并进入纵向功能磁化 磁共振成像(MRI)方案。将获得大脑静息状态功能连接(RSFC)MRI数据 出生前后的纵向3倍，从胎龄25周到出生后12周 年龄。第一步中关于网络涌现的发现将为后续的评估提供基础 宫内脑成熟与儿童期发育成就的关系 为此，将在现有的110名学龄前儿童样本中测量自我调节行为，这些样本 4年前接受了胎儿脑部RSFC成像。在这些参与者中，母体之间的联系 将检查产前应激、胎儿大脑功能连通性和儿童神经行为发育。 这个项目的主要目的是(I)在我们对整体的出现的理解上开辟新的天地 开始于胎儿生命的大脑功能回路，(Ii)识别产前大脑连接的变异，可能 使4岁儿童容易延迟完成预示生命的关键发育里程碑 以及(Iii)检查产前应激对紧急胎儿大脑功能连通性的影响。 由于其创新的重点是胎儿RSFC的先兆、脆弱性和后果，该项目是理想的 适用于NIMH Brains奖，旨在支持在 实施高影响力、新颖性研究。这些研究目标的启动和实现将是 职业生涯的第一步，专注于确定早期发育风险所通过的神经生物学途径 可能会被授予，也可能最终被阻止。

PROJECT SUMMARY The human fetal brain is complex, highly plastic, and extremely vulnerable. Mild variation in utero can drastically impair life-long learning and neurological health. Despite growing appreciation for the relevance of this period to numerous developmental, psychiatric and neurological disorders, macroscale functional organization of the fetal brain remains a `black box' for neuroscience research. While there are phenomenal technologies for examining fetal brain anatomy, only very recently have we possessed non-invasive means of studying coordinated function in the living human fetal brain. This project is focused on understanding the emergence of whole brain functional circuitry beginning in fetal life, and identifying relationships between prenatal brain connectivity and preschoolers' attainment of key developmental milestones. Given that the womb is the first environment for the fetus, and is thus the place where biology and environment first interact, we will also examine the effects of prenatal stress exposure on human fetal brain functional connectivity. Sixty women will be recruited in weeks 25-32 of pregnancy and entered into a longitudinal functional magnetic resonance imaging (MRI) protocol. Brain resting-state functional connectivity (RSFC) MRI data will be obtained 3x longitudinally prior to and following birth, spanning ages 25 weeks gestational age to 12 weeks postnatal age. Discoveries about network emergence in this first step will provide a basis for subsequent evaluation of the relationship between brain maturation in utero and attainment of developmental milestones in childhood. To this end, self-regulatory behavior will then be measured in an existing sample of 110 preschoolers that underwent fetal brain RSFC imaging 4 years ago. In these participants, associations between maternal prenatal stress, fetal brain functional connectivity, and child neurobehavioral development will be examined. The primary aims of this project are to (i) break new ground in our understanding of the emergence of whole brain functional circuitry beginning in fetal life, (ii) identify variations in prenatal brain connectivity that may predispose 4-year-old children to delayed attainment of key developmental milestones that prognosticate life long health, and (iii) examine the influence of prenatal stress on emergent fetal brain functional connectivity. With its innovative focus on precursors, vulnerability, and consequences of fetal RSFC, this project is ideally suited to the NIMH BRAINS award aiming to support a productive early stage investigator in the implementation of high-impact, novel research. Initiation and achievement of these research aims will be the first step in a career focused on identifying neurobiological pathways through which early developmental risk may be conferred and also ultimately prevented.