Longitudinal Investigation of the Neurobiological Underpinnings of Risk Behavior in ADHD throughout the Adolescent Transition: The Key Role of Cognitive Control and Motivation Network Development

项目摘要/摘要 注意力缺陷/多动障碍(ADHD)是儿童最常见的发育障碍。 儿童，影响到全国约9%的儿童。尽管ADHD极大地增加了穷人的风险 关于学业成就、滥用药物和犯罪行为，尤其是在青春期，我们知之甚少。 关于神经生物学发展轨迹是如何支撑这些行为和临床结果的。这 尽管这种工作对于更早、更有针对性地识别风险因素很重要，但情况依然如此 治疗模式，反过来，教育、青少年司法和个人、家庭和医疗保健储蓄 社会。因此，当前项目的目标是描述纵向神经、行为和临床的特征 儿童多动症青少年从儿童期末期到青春期中期的轨迹。认知基础的大脑系统 尤其是控制和动机已被认为是中枢重要的两个神经病因学 ADHD和冒险行为的普遍增加以及糟糕的决策在典型的 发育期(TD)青少年。这些模型的一个重要方面是大脑中这些区域是如何 过程形成连贯的网络，以及这些网络如何相互作用和影响以产生 行为。在这里，我们将这两个完全不同的文献结合在一起，以了解向 青少年ADHD的青春期。因此，本研究着眼于认知控制的成熟过程。 和激励系统，单独和互动，在多个疗程中患有和不患有ADHD的青少年 纵向设计。这一建议的目的包括：1)表征认知控制的行为轨迹， ADHD和TD青少年从童年到青春期的动机及其相互作用；2)表征 在同一时期发展结构性和功能性的脑网络组织，重点是 认知控制和动机的大脑网络；以及3)识别神经、行为和临床 青春期前ADHD的特征可以预测青春期的临床结果和冒险行为。至 为了满足这些目标，基于图论和结构方程建模的创新网络分析工具 将应用于弥散加权成像期间MRI数据的结构和功能连通性估计 (结构性)和在休息期间，认知控制、动机和冒险任务(功能性)。这些技术是 独一无二地能够同时表征网络内部结构/功能的强度和一致性 连接性和跨网络交互，以及识别重要的大脑网络功能 在不同群体之间实现差异化。此外，在认知控制、动机和风险上的行为表现- 将评估接受任务、ADHD症状以及冒险态度和行为。这是一项 研究直接符合NIH战略计划，并建立在RDoC框架上。加在一起，这些 这些发现将为及早识别并最终预防ADHD提供基础 在青春期更有可能导致不良后果的轨迹。

PROJECT SUMMARY/ABSTRACT Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed developmental disorder of childhood, affecting ~9% of children nationwide. Although ADHD dramatically increases the risk for poor academic achievement, substance abuse, and criminal behavior, particularly in adolescence, too little is known regarding how neurobiological developmental trajectories underlie these behavioral and clinical outcomes. This remains the case in spite of the importance of such work for earlier identification of risk factors, more targeted treatment models, and, in turn, education, juvenile justice, and healthcare savings for individuals, families, and society. The goal of the current project, therefore, is to characterize longitudinal neural, behavioral, and clinical trajectories of youth with ADHD from late childhood to mid-adolescence. Brain systems underlying cognitive control and motivation in particular have been identified as centrally important both to the neural etiology of ADHD and to the general increase in risk-taking behavior and poor decision-making observed in typically developing (TD) adolescents. An important aspect of these models is how brain regions underlying these processes form coherent networks, as well as how these networks interact and influence each other to produce behavior. Here we bring together these two disparate literatures to gain understanding of the transition to adolescence in youth with ADHD. Thus, this proposal focuses on the maturational course of the cognitive control and motivation systems, individually and in interaction, in youth with and without ADHD in a multi-session longitudinal design. The aims of this proposal include: 1) Characterize behavioral trajectories of cognitive control, motivation, and their interaction in ADHD and TD youth from childhood into adolescence; 2) Characterize the development of structural and functional brain network organization during the same time period, focusing on brain networks underlying cognitive control and motivation; and 3) Identify neural, behavioral, and clinical features of pre-adolescent ADHD that predict clinical outcomes and risk-taking behavior during adolescence. To address these aims, innovative network analytic tools based on graph theory and structural equation modeling will be applied to structural and functional connectivity estimates of MRI data during diffusion-weighted imaging (structural) and during rest, cognitive control, motivation, and risk-taking tasks (functional). These techniques are uniquely able to simultaneously characterize the strength and coherence of within-network structural/functional connectivity and across-network interactions, as well as to identify important brain network features that differentiate across groups. Additionally, behavioral performance on the cognitive control, motivation and risk- taking tasks, ADHD symptomatology, and risk-taking attitudes and behavior will be assessed. This program of research is directly in line with the NIH Strategic Plan and builds on the RDoC framework. Together, these findings will provide the groundwork that can lead to early identification and, ultimately, prevention of ADHD trajectories that are more likely to lead to adverse outcomes in adolescence.