Brain trajectories in ADHD

项目摘要 ADHD长期以来一直被认为包括基于大脑的病理生理学，但最新的方法， 迄今为止，描述ADHD中非典型脑组织的研究仅限于横断面研究。当前 该项目旨在研究青春期ADHD变化的神经生物学相关性这一关键问题。在 在青春期，ADHD的结果开始在一些重要的方面出现分歧，但这些方面的解释却很差。了解 这些临床变化的神经生物学基础将在临床理解方面向前迈出重要一步。在 与此同时，在青春期，大脑功能发育的动力学是非线性的，与 这些过程在儿童时期，这表明更深入地关注这一年龄段。建立在一个概念上 框架，整合认知和情绪回路在大脑中，本研究有以下内容 主要目标。首先，它试图发现ADHD患者大脑组织的不同类型 青少年期ADHD病程的人群预测。其次，它试图跟踪发展中的变化， ADHD人群中的跨网络大脑组织与不同临床发展的关系 在青少年时期。第三，它试图评估基于大脑发育的“神经类型”的前景。 注意力缺陷多动症这一努力的意义在于其前所未有的能力， 神经生物学随着时间的推移与大脑表征的方法，尚未在ADHD检查 纵向以这种方式之前，并在其努力移动大脑成像到临床预测领域使用 纵向设计。该项目是创新方面的实施网络和拓扑结构的特点， 多波设计中的大脑分析，识别ADHD的基于大脑的类型学（神经生物学 异质性），并将这些与临床过程联系起来。该方法需要跟踪已经制定的 采用交叉滞后纵向设计，对376名儿童进行队列研究，以表征不同年龄段的发育特征 7-19年脑组织将通过弥散张量成像和静息状态功能进行操作化 连接，同时也将提供标准的结构指标。青年将每年在 与临床症状、合并症、损伤、认知功能、奖励折扣和情绪的关系 监管和运作。分析方法将跨越大脑回路，网络和拓扑测量 使用新的图论分析来描述大脑系统。将评价临床类型学 使用社区检测程序和多标准混合模型分析大脑特征。潜 类轨迹模型将被用来探索不同的发展类型的多动症，如果他们存在。目标 直接匹配NIMH战略计划的关键优先事项。如果成功，该项目有望打破僵局 面对该领域的临床实用性方面的日益掌握的非典型脑生理学在多动症。所有原始 和处理/清理的数据正在提供给外地勘探，以最大限度地利用这一点 一种类型的队列。

Project Summary ADHD has long been believed to include brain-based pathophysiology, but the newest approaches to describing atypical brain organization in ADHD are thus far limited to cross-sectional studies. The current project aims at the crucial question of the neurobiological correlates of change in ADHD during adolescence. In adolescence, ADHD outcomes begin to diverge in important ways that are poorly explained. Understanding the neurobiological basis of those clinical changes would provide a major step forward in clinical understanding. At the same time, in adolescence the dynamics of functional brain development are non-linear and distinct from those processes in childhood, suggesting a deeper focus on that age period. Building on a conceptual framework that integrates cognitive and emotional circuitries in the brain, the present study has the following principal objectives. First, it seeks to discover how distinct types of brain organization within the ADHD population predict in ADHD course during adolescence. Second, it seeks to track variations in the development of cross-network brain organization within the ADHD population in relation to divergent clinical development during the adolescent period. Third, it seeks to evaluate prospects for developmental brain-based “neurotypes” in ADHD. The significance of this effort lies both in its unprecedented ability to characterize ADHD neurobiology over time with methods of brain characterization that have not been examined in ADHD longitudinally in this way before, and in its effort to move brain imaging into the realm of clinical prediction using a longitudinal design. The project is innovative in regard to implementing network and topology features of brain analysis in a multi-wave design, identifying brain-based typologies of ADHD (neurobiological heterogeneity), and linking these to clinical course. The approach entails tracking of an already developed cohort of 376 children in a cross-lagged longitudinal design, enabling characterization of development from age 7-19 years. Brain organization will be operationalized with diffusion tensor imaging and resting state functional connectivity, while standard structural metrics will also be available. Youth will be characterized annually in relation to clinical symptoms, comorbidity, impairment, cognitive functioning, reward discounting, and emotion regulation and functioning. Analytic approaches will span brain circuit, network, and topological measurements using novel graph theoretical analyses to characterize brain systems. Clinical typologies will be evaluated using community detection procedures and more standard mixture model analysis of brain features. Latent class trajectory models will be used to explore distinct developmental types of ADHD if they exist. The Aims directly match key priorities of the NIMH strategic plan. If successful, the project hopes to break the impasse facing the field with regard to clinical utility of the growing grasp of atypical brain physiology in ADHD. All raw and processed/cleaned data are being made available to the field for exploration to maximize the utility of this one of a kind cohort.