Early neurobiological predictors of executive functioning in toddlers

幼儿执行功能的早期神经生物学预测因素

• 批准号: 9143802
• 负责人: Alice M Graham
• 金额: $ 5.61万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-03 至 2017-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9143802
• 关键词: 1 year old; 2 year old; Adult; Advanced Development; Affect; Age; Area; Area Under Curve; Attention; Awareness; Behavior; Behavior assessment; Behavioral; Biological; Biological Markers; Birth; Brain; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Childhood; Communities; Community Integration; Community Networks; Computing Methodologies; Data Collection; Data Set; Development; Diamond; Dorsal; Early Intervention; Early identification; Environment; Exposure to; Fellowship; Fetus; Foundations; Funding; Goals; Health; Hydrocortisone; Individual; Individual Differences; Infant; Interdisciplinary Study; Intervention; Life; Light; Link; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Mental Health; Mental disorders; Methods; Modeling; Neonatal; Neurobiology; Parietal; Pathway Analysis; Pattern; Phenotype; Placenta; Pregnancy; Process; Psychopathology; Psychosocial Stress; Regulation; Research; Research Methodology; Rest; Risk; Risk Marker; School-Age Population; Schools; Services; Shapes; Short-Term Memory; Social Functioning; Source; Special Education; Stress; Structure; Support System; Symptoms; System; Testing; Time; Toddler; Training; United States; United States National Institutes of Health; Work; career development; cognitive development; cognitive process; cost; density; early childhood; education financing; executive function; fetal; in utero; indexing; infancy; innovation; postnatal; prenatal; prenatal influence; prenatal stress; programs; segregation; skills; statistics; support network

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.

描述(由申请人提供)：从事有目的的、目标导向的行为的能力，称为执行功能(EF)，为心理健康、学术和社会功能提供基础。因此，EF是旨在降低精神病和学校困难风险的早期干预服务的目标。然而，由于在2岁之前评估EF的难度，有针对性的干预努力受到限制。静息状态功能连接性 磁共振成像(rS-fcMRI)可以评估从新生儿期开始的EF所涉及的大脑系统。RS-fcMRI应用的先进计算方法揭示了大脑组织成可分离的功能网络的过程，这些网络支持高级认知过程，如EF。目前的提案试图应用这些方法来检查婴儿期的大脑功能网络，作为2岁时出现的EF技能的预测指标，届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外，检查这些大脑网络还有可能阐明早期环境对EF的影响。出生前的压力和童年时期的EF困难之间的联系被认为是通过大脑发育轨迹的改变来解释的。然而，产前压力、早期大脑发育和新兴的EF技能之间的假设联系尚未得到测试。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，该数据集包括 出生前和出生后环境的广泛特征，婴儿在2周和1岁时进行RS-fcMRI扫描，并在2岁时进行EF评估。她将使用先进的计算方法来表征与EF有关的功能性大脑网络的发育，以及从出生到1岁的整个大脑拓扑(社区结构)。这些大脑指标将在2岁时作为EF技能的预测指标进行检验(目标1)。产前孕妇皮质醇将作为宫内生物应激暴露的一个指标进行检查，这可能是多种心理社会应激对胎儿大脑发育影响的一个途径。申请者将检查累积的产前压力暴露和特定敏感期(三个月)的压力，作为与EF技能相关的大脑指标的预测因子。最后，应用程序将测试一个完整的中介模型，通过功能大脑来研究产前应激对EF的影响 发展(目标2)。这项工作有可能阐明EF不良的早期神经生物学标记物，以及EF下大脑系统发育的敏感期。这种纵向、多方法的研究对于开发将早期应激暴露、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。研究金培训将侧重于特定的内容领域，包括产前应激和大脑发育、rs-fcMRI的高级计算方法、纵向多变量统计和EF。重要的是，培训还将强调特定于申请者计划的研究计划的职业发展目标，包括对协作跨学科研究的关注。