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

项目摘要 人类胎儿的大脑是复杂的，高度可塑的，并且非常脆弱。子宫内的轻度变异可以 严重损害终身学习和神经健康。尽管人们越来越认识到 这一时期的许多发展，精神和神经系统疾病，宏观功能 胎儿大脑的组织仍然是神经科学研究的“黑匣子”。虽然有惊人的 检查胎儿大脑解剖结构的技术，直到最近我们才拥有非侵入性的手段， 研究人类胎儿大脑的协调功能。该项目的重点是了解 整个大脑功能回路的出现始于胎儿期，并确定 产前大脑连接和学龄前儿童达到关键的发展里程碑。鉴于 子宫是胎儿的第一个环境，因此是生物和环境第一次相互作用的地方， 我们还将研究产前应激暴露对人类胎儿脑功能连接的影响。六十 妇女将在怀孕25-32周招募，并进入纵向功能磁 共振成像（MRI）方案。将获得大脑静息状态功能连接（RSFC）MRI数据 出生前后纵向3次，年龄跨度为胎龄25周至产后12周 年龄在这第一步中关于网络涌现的发现将为随后的评估提供基础。 子宫内大脑成熟与儿童期发育里程碑的实现之间的关系。 为此，自我调节行为将在现有的110名学龄前儿童的样本中进行测量， 四年前接受了胎脑RSFC成像在这些参与者中， 产前压力，胎儿脑功能连接，和儿童神经行为发育将被检查。 这个项目的主要目的是（i）在我们对整体的出现的理解中开辟新的天地 在胎儿生命开始的脑功能电路，（ii）确定产前脑连接的变化， 使4岁的儿童容易延迟达到关键的发展里程碑， 长期健康，和（iii）检查产前压力对胎儿脑功能连接的影响。 由于其创新的重点是胎儿RSFC的前兆，脆弱性和后果，该项目是理想的 适合NIMH大脑奖，旨在支持一个富有成效的早期阶段的调查， 实施高影响力、新颖的研究。这些研究目标的启动和实现将是 职业生涯的第一步，重点是确定神经生物学途径，通过这些途径，早期发育风险 可能会被赋予，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.