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，并在整个过程中受损。 多种精神疾病，如多动症和精神病。尽管如此，EF的神经基质 发展还不完全清楚。在这里，我们建议使用切割来研究EF的发展- 网络科学的边缘技术。在这个计划中，我们将招募140名10-16岁的参与者。这 样本将包括50名ADHD患者，50名精神病谱系诊断患者和40名典型发展中国家的儿童。 比较仪.使用加速纵向设计，所有参与者将被跟踪并接受认知 测试，临床评估，和先进的多模态神经成像在18个月的时间间隔，产生一个 平均每名学员2.5节课。这种设计将使我们能够绘制结构和 功能性大脑网络在青春期，并描绘如何异常的大脑网络的发展 与EF表现、激活和动力学缺陷相关。我们的首要假设是 在青春期，模块化但整合的大脑网络的发展允许特定的模式， EF激活和动力学，并代表EF发展的基本机制。我们将其 网络发育异常与执行功能障碍有关， 存在于精神疾病如多动症和精神病中。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，并定义如何 网络发育异常与ADHD青少年的EF缺陷有关， 精神病在目标2中，我们将定义大脑网络拓扑结构的异常发展如何与 执行激活和动态的改变。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来创建执行功能障碍的维度预测器。 最后，在目标4中，我们将共享原始数据和处理后的数据，为 神经科学社区这项建议利用了PI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、认知科学和高等教育方面的专业知识。 三维成像统计。通过多层次的分析，本研究将提供 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 在青少年精神疾病中的作用

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.