Characterizing pubertal and age mechanisms of neurodevelopment and association with rising internalizing symptoms

项目摘要 建立从童年到成年早期的人类大脑发育的全面帐户至关重要， 我们对健康的神经发育和对青少年心理健康威胁的潜在机制的理解， 健康大脑发育在多个层面上展开，但该领域缺乏对大脑发育的全面了解。 发展轨迹在不同模式之间是基本相似还是不同（例如，结构 和功能），以及它们如何反映与青春期或年龄（或两者）相关的发育机制。的 拟议的研究旨在产生一个系统和全面的多模态帐户的典型 从5岁到21岁的神经发育，特别关注a）识别年龄与青春期， 儿童和青少年发展的基础性机制; B）系统性 使用最先进的采集和分析技术对大脑结构、功能和连接进行分析 方法;以及c）评估跨大脑系统的多模态耦合中的成熟变化。 模式作为发展的一个功能。一旦建立，这种典型神经发育的多模式模型 将用于测试一个概念模型，该模型提出青春期提前会导致 由于大脑发育的中断，包括多模态耦合的改变而引起的内在症状。 具体来说，青春期提前的影响模型预测， 青春期（神经发育加速）或由于神经发育延迟导致的耦合中断。到 比较这些相互竞争的模型，并通过以下方式促进我们对神经发育途径的理解： 研究表明，青春期早期的哪个时间点会导致青春期内在症状的增加， 将使用假设驱动的方法和新的验证分析管道进行数据驱动的探索， 发展变化的耦合，仔细注意鲁棒性和复制。主数据集 将是人类连接组开发项目（HCPD），一个由NIH资助的大型多模式大脑 成像数据集，包括对大脑结构、功能和连接性的全面评估， 青春期和激素的措施和广泛的行为和临床措施，在这两个横截面 N=1300+ 5至21岁青年的队列，以及年龄为9至17岁的纵向队列（N=252）， 青春期过渡这个样本在种族、民族和社会经济地位上有很强的多样性。 将复制主要发现，以确保青少年大脑和认知功能的稳健性和普遍性。 发展（ABCD）纵向研究。我们的具体目标是：A1）建立一个全面、系统的 在大脑结构的多种模式中，与年龄和青春期相关的大脑发育途径的说明 A2）测试关于年龄和青春期发育与跨性别耦合的关系的假设 A3）测试有关神经发育机制的假设，有助于提高 在青春期过渡期内内化症状。

PROJECT SUMMARY Building comprehensive accounts of human brain development from childhood to early adulthood is crucial to our understanding of both healthy neurodevelopment and the mechanisms underlying threats to youths’ mental health. Brain development unfolds on multiple levels, but the field lacks a comprehensive understanding of whether the trajectories of development are fundamentally similar or different across modalities (e.g., structure and function), and how they reflect developmental mechanisms associated with puberty or age (or both). The proposed research aims to generate a systematic and comprehensive multimodal account of typical neurodevelopment from ages 5 to 21, with a particular focus on a) identifying age versus pubertal- and hormonal-based mechanisms that undergird development in childhood and adolescence; b) systematic analyses across brain structure, function, and connectivity using state-of-the-art acquisition and analysis approaches; and c) evaluation of maturational variation in multimodal coupling across brain systems/ modalities as a function of development. Once established, this multimodal model of typical neurodevelopment will be used to test a conceptual model proposing that early pubertal timing leads to intensification of internalizing symptoms due to disruptions in brain development, including alterations in multimodal coupling. Specifically, models of the impact of early pubertal timing predict either further enhanced coupling with early puberty (neurodevelopmental acceleration) or disruptions in coupling due to neurodevelopmental delays. To compare these competing models and advance our understanding of the neurodevelopmental pathways by which early pubertal timing contributes to the rise of internalizing symptoms during adolescence, the research will use both hypothesis-driven methods and novel validated analysis pipelines for data-driven exploration of developmental changes in coupling, with careful attention to robustness and replication. The primary dataset will be the Human Connectome Project in Development (HCPD), a large, NIH funded, multimodal brain imaging dataset that includes a comprehensive assessment of brain structure, function, and connectivity paired with pubertal and hormonal measures and extensive behavioral and clinical measures in both a cross-sectional cohort of N=1300+ youth ages 5 to 21, and a longitudinal cohort (N=252) spanning ages 9 to 17 capturing the pubertal transition. This sample is purposefully strong diversity in race, ethnicity, and socioeconomic status. Key findings will be replicated to ensure robustness and generalizability in the Adolescent Brain and Cognitive Development (ABCD) longitudinal study. Our Specific Aims are to: A1) Establish a comprehensive, systematic account of age-and pubertal-linked pathways of brain development across multiple modalities of brain structure and function; A2) Test hypotheses about the relations of age and pubertal development to coupling across brain modalities; and A3) Test hypotheses about the neurodevelopmental mechanisms contributing to the rise in internalizing symptoms during the pubertal transition.