Early neurobiological predictors of executive functioning in toddlers

描述（由申请人提供）：从事有目的的，目标导向的行为的能力，被称为执行功能（EF），为心理健康，学术和社会功能提供了基础。因此，EF是早期干预服务的目标，旨在减少精神病理学和学校困难的风险。然而，有针对性的干预措施受到2岁之前评估EF的困难的限制。静息态功能连通性 MRI（rs-fcMRI）允许在新生儿期开始评估与EF有关的脑系统。应用rs-fcMRI的先进计算方法已经揭示了大脑组织成可分离的功能网络，支持高水平的认知过程，如EF。目前的建议旨在应用这些方法来检查婴儿期的功能性大脑网络，作为2岁时新兴EF技能的预测因子，此时可靠的行为评估成为可能。除了增加对可观察到的EF技能之前的神经发育过程的理解之外，检查这些大脑网络有可能阐明EF的早期环境影响。产前压力和儿童时期EF困难之间的关联被认为是由大脑发育的轨迹改变来解释的。然而，产前压力，早期大脑发育和新兴EF技能之间的假设联系尚未得到验证。根据目前的提议，申请人将在一个独特的纵向数据集中测试这些连接， 产前和产后环境的广泛表征，婴儿2周龄和1岁时的rs-fcMRI扫描，以及2岁时的EF评估。她将采用先进的计算方法来表征EF中涉及的功能性脑网络的发展，以及从出生到1岁的全脑拓扑结构（社区结构）。这些大脑指标将作为2岁时EF技能的预测因素进行检查（目标1）。产前母体皮质醇将作为子宫内生物应激暴露的指标进行检查，这可能是多种心理社会应激源对胎儿大脑发育影响的一个指标。申请人将检查特定敏感期（妊娠期）的累积产前压力暴露和压力，作为与EF技能相关的大脑指标的预测因素。最后，applicat将通过功能脑测试产前应激对EF影响的完全中介模型 发展（目标2）。这项工作有可能阐明EF差风险的早期神经生物学标志物，以及EF相关脑系统发育的敏感时期。这种纵向的、多方法的研究对于开发将早期压力暴露、大脑发育和与心理健康相关的行为表型联系起来的综合模型至关重要。奖学金培训将集中在特定的内容领域，包括产前压力和大脑发育，rs-fcMRI的先进计算方法，纵向多变量统计和EF。重要的是，培训还将强调特定于申请人计划的研究计划的职业发展目标，包括专注于跨学科合作研究。

DESCRIPTION (provided by applicant): The capacity to engage in purposeful, goal-directed behaviors, known as executive functioning (EF), provides a foundation for mental health, and academic and social functioning. EF is therefore a target for early intervention services aimed at reducing risk for psychopathology and school difficulties. However, targeted intervention efforts are limited by the difficulty of assessing EF prior to age 2. Resting state functional connectivity MRI (rs-fcMRI) allows for assessment of brain systems implicated in EF beginning in the neonatal period. Advanced computational methods applied with rs-fcMRI have shed light on the organization of the brain into dissociable functional networks that support high level cognitive processes, such as EF. The current proposal seeks to apply these methods to examine functional brain networks during infancy as predictors of emerging EF skills at 2 years of age, when reliable behavioral assessment becomes possible. In addition to increasing understanding of the neurodevelopmental processes preceding observable EF skills, examining these brain networks has potential to elucidate early environmental influences on EF. Associations between prenatal stress and difficulties with EF in childhood are thought to be explained by altered trajectories of brain development. However, hypothesized connections between prenatal stress, early brain development and emerging EF skills have not been tested. Under the current proposal, the applicant will test these connections in a unique longitudinal data set that includes extensive characterization of the pre- and postnatal environment, infant rs-fcMRI scans at 2 weeks and 1 year of age, and EF assessment at 2 years. She will employ advanced computational methods to characterize development of functional brain networks implicated in EF, and whole brain topology (community structure) from birth to 1 year of age. These brain metrics will be examined as predictors of EF skills at 2 years of age (Aim 1). Prenatal maternal cortisol will be examined as an index of in utero biological stress exposure that is a likely condut for the effects of multiple sources of psychosocial stress on fetal brain development. The applicant will examine cumulative prenatal stress exposure and stress during specific sensitive periods (trimesters) as predictors of brain metrics associated with EF skills. Finally, the applicat will test a full mediational model of the effects of prenatal stress on EF through functional brain development (Aim 2). This work has potential to shed light on early neurobiological markers of risk for poor EF, and sensitive periods in the development of brain systems underlying EF. Longitudinal, multi-method research of this kind is essential for developing comprehensive models linking early stress exposure, brain development and behavioral phenotypes relevant to mental health. Fellowship training will focus on specific content areas, including prenatal stress and brain development, advanced computational methods for rs-fcMRI, longitudinal multivariate statistics, and EF. Importantly, training will also emphasize career development objectives specific to the applicant's planned program of research, including a focus on collaborative interdisciplinary research.