Longitudinal Mapping of Network Development Underlying Executive Dysfunction in Adolescence

摘要 执行功能(EF)在青春期经历了戏剧性的发展，并随着年龄的增长而受损 多发性精神障碍，如多动症和精神病。尽管如此，EF的神经基质 人们对发展的理解还不够全面。在这里，我们建议研究生态足迹的发展，使用切割- 来自网络科学的前沿技术。在这项提案中，我们将招募140名年龄在10-16岁的参与者。这 样本将包括50名ADHD患者，50名患有精神病谱系诊断的患者，40名典型的发展中患者 比较器。使用加速纵向设计，所有参与者都将被跟踪并接受认知 每隔18个月进行一次测试、临床评估和先进的多模式神经成像，产生 每个参与者平均2.5次会议。这一设计将使我们能够绘制出结构和 青春期功能大脑网络，并描绘了大脑网络发育的异常 与EF表现、激活和动力学方面的缺陷有关。我们最重要的假设是 在青春期，模块化但集成的大脑网络的发展允许特定的模式 EF的激活和动力学，是EF发育的基本机制。我们假设 网络发育的异常将与维度上的执行功能障碍相关 存在于多动症和精神病等精神障碍中。因此，在本提案的目标1中，我们 将绘制结构和功能大脑网络的纵向发展图，并定义 青少年ADHD患者网络发育异常与维度EF缺陷相关 精神错乱。在目标2中，我们将定义大脑网络拓扑结构的异常发展如何与 执行力和能动性的改变。在目标3中，我们将整合高维成像数据 使用先进的多变量分析技术创建执行功能障碍的维度预测因子。 最后，在目标4中，我们将共享原始数据和经过处理的数据，为 神经科学界。这项提议充分利用了私人投资机构和研究团队的互补技能， 包括大脑发育、网络科学、精神病理学、认知科学和高级 维度成像统计。通过建议的多层次分析，这项创新研究将提供 我们对执行功能障碍的神经发育基础的理解有了实质性的进展 青春期的精神障碍。

ABSTRACT Executive function (EF) undergoes dramatic development during adolescence, and is impaired across multiple psychiatric disorders such as ADHD and psychosis. Despite this fact, the neural substrates of EF development remain incompletely understood. Here, we propose to study the development of EF using cutting- edge techniques from network science. In this proposal, we will recruit 140 participants ages 10-16. This sample will include 50 with ADHD, 50 with psychosis-spectrum diagnoses, and 40 typically developing comparators. Using an accelerated longitudinal design, all participants will be followed and undergo cognitive testing, clinical assessment, and advanced multi-modal neuroimaging at 18 month intervals, yielding an average of 2.5 sessions per participant. This design will allow us to chart the development of structural and functional brain networks during adolescence, and delineate how abnormalities of brain network development are associated with deficits in EF performance, activation, and dynamics. Our overarching hypothesis is that the development of modular yet integrated brain networks during adolescence allows for specific patterns of EF activation and dynamics, and represents a fundamental mechanism for EF development. We posit that abnormalities of network development will be associated with executive dysfunction that is dimensionally present across psychiatric disorders such as ADHD and psychosis. Accordingly, in Aim 1 of this proposal, we will chart the longitudinal development of both structural and functional brain networks, and define how abnormalities of network development are associated with dimensional EF deficits in youth with ADHD and psychosis. In Aim 2, we will define how abnormal development of brain network topology is associated with alterations of executive activation and dynamics. In Aim 3, we will integrate high-dimensional imaging data using advanced multivariate analytic techniques to create a dimensional predictor of executive dysfunction. Finally, in Aim 4, we will share both raw and processed data, creating a valuable new resource for the neuroscience community. This proposal capitalizes on complementary skills of the PIs and the research team, including expertise in brain development, network science, psychopathology, cognitive science, and high dimensional imaging statistics. Through the proposed multi-level analysis, this innovative research will provide a substantial advance in our understanding of the neurodevelopmental substrates of executive dysfunction across psychiatric disorders in adolescence.