Longitudinal Mapping of Network Development Underlying Executive Dysfunction in Adolescence

青春期执行功能障碍背后的网络发展的纵向映射

• 批准号: 10112308
• 负责人: Danielle Smith Bassett
• 金额: $ 71.56万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10112308
• 关键词: Address; Adolescence; Adolescent; Age; Attention deficit hyperactivity disorder; Back; Brain; Brain region; Clinical; Clinical assessments; Cognition; Cognitive; Cognitive Science; Communities; Complex; Data; Development; Diagnosis; Dimensions; Disease; Equation; Evolution; Executive Dysfunction; Failure; Fractals; Graph; Image; Impairment; Link; Machine Learning; Magnetic Resonance Imaging; Measures; Mediating; Mental disorders; Modeling; Multimodal Imaging; Neurosciences; Outcome; Parietal; Participant; Pattern; Performance; Process; Property; Psychopathology; Psychoses; Public Health; Research; Resources; Risk-Taking; Sampling; Schizophrenia; Science; Short-Term Memory; Societies; Structure; System; Systems Analysis; Techniques; Testing; Time; Visit; Wolves; Youth; base; brain abnormalities; cognitive testing; cost; data resource; design; disability; effective therapy; executive function; flexibility; high dimensionality; indexing; innovation; longitudinal design; multilevel analysis; multimodality; neuroimaging; prisma; recruit; relating to nervous system; skills; software development; statistics; theories

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.

抽象的 执行功能（EF）在青春期内经历了戏剧性的发展，并受到损害 多种精神疾病，例如多动症和精神病。尽管这一事实，EF的神经底物 发展仍然不完全理解。在这里，我们建议使用剪切研究EF的发展 - 网络科学的边缘技术。在此提案中，我们将招募140名10-16岁的参与者。这 样本将包括50个ADHD，50个具有精神病谱诊断的样本，以及40个通常会发育的 比较器。使用加速的纵向设计，将遵循所有参与者并接受认知 测试，临床评估和高级多模式神经成像以18个月的间隔产生 平均每个参与者会议。这种设计将使我们能够绘制结构和 青春期功能性脑网络，并描述大脑网络发展的异常 与EF性能，激活和动态缺陷有关。我们的总体假设是 青春期模块化但整合大脑网络的发展允许特定模式 EF激活和动力学，代表EF开发的基本机制。我们认为 网络开发的异常将与执行功能障碍有关，这是维度的 跨精神病疾病（如多动症和精神病）存在。因此，在本提案的目标1中，我们 将绘制结构和功能性脑网络的纵向发展，并定义如何 网络发展的异常与ADHD和ADHD青年的尺寸EF缺陷有关 精神病。在AIM 2中，我们将定义大脑网络拓扑的异常发展与 执行激活和动态的改变。在AIM 3中，我们将集成高维成像数据 使用先进的多元分析技术来创建执行功能障碍的维度预测指标。 最后，在AIM 4中，我们将共享原始数据和处理的数据，为该数据创建有价值的新资源 神经科学社区。该提案大写了PIS和研究团队的互补技能， 包括大脑发展，网络科学，心理病理学，认知科学和高级专业知识 维成像统计。通过拟议的多层次分析，这项创新的研究将提供 我们对执行功能障碍的神经发育底物的理解有很大的进步 青春期的精神疾病。