Developmental Changes in Neural Processes Underlying Inattention, Impulsivity and Regulation

冲动问题与公共健康有重大关系，因为它们不仅影响个人 而且是整个社会。高冲动与无数不好的结果有关，包括 精神病理学，药物使用障碍，低教育和职业素养，身体健康状况差， 和高事故率[11-17]。冲动表现在一种光谱上，注意力缺陷者/ 多动障碍(ADHD)位于连续体的极端。在本修订的竞争对手R01续订中，我们 提出了四个时间点的纵向研究设计，在前两个时间点的基础上增加了两个时间点的获取 使用基于任务的功能和扩散张量(DTI)神经成像数据获取初始队列，其中 对情绪功能如何与冲动有关的新强调。要解决的维度性质 我们还将添加一组具有亚临床冲动评级的个人，来探索如何充分 随着时间推移，冲动的范围和持久性会影响结果。我们现在将把年龄范围从 在以前招募的神经典型患者(NT)中12至25岁至15至30年的初始数据收集和 患有ADHD的参与者。我们将重点关注与冲动相关的结果，这些结果更有可能在15年出现 到30岁的年龄跨度，如易怒、情绪不稳定、精神和药物使用障碍、自残 还有自杀未遂，以及学业和职业障碍。我们假设， (1)背外侧前额叶皮质(DLPFC)和纹状体背侧通路之间的结构联系 预测冲动性的个体差异，在DLPFC和背侧之间有更大的负耦合 纹状体与更强的冲动控制有关。我们假设，这种联系将随着成熟而加强。我们 还假设增加腹侧纹状体和杏仁核之间的连接强度将 预测更冲动的行为。我们的目标是在多模式(fMRI，DTI，行为)纵向 影像调查：(A)这些变化是如何从青春期早期到成年初期出现的，以及(B) 这些发展变化如何反映在从典型到高尚和有意义的人身上 冲动。此外，我们还将评估ADHD患者之间的大脑连接和行为差异 继续做出冲动决定的人(持久者)与不再冲动的人 在过渡到青壮年期间的决定(汇款)。我们还将评估这些系统如何发挥作用 神经系统(如DLPFC和纹状体)可能受到应激性和程度的调节，并与之相关 情绪调节。从最初的拨款扩展一个目标，我们将测试大脑功能与 和真实世界的功能，包括职业成就，精神病的存在，自我伤害，以及 物质使用障碍。我们还将评估哪些因素会带来更大的韧性。在我们的研究结束时 我们将确定特定年龄的目标，在一段时间内减少冲动和防止自我伤害 更多的脆弱性和机会。

Problems with impulsivity are of major relevance to public health as they affect not only individuals but also society as a whole. High impulsivity is associated with a myriad of poor outcomes including psychopathology, substance use disorders, low educational and occupational attainment, poor physical health, and high accident rates [11-17]. Impulsivity presents on a spectrum and persons with attention-deficit/ hyperactivity disorder (ADHD) lie at the extreme of the continuum. In this revised competing R01 renewal we propose a four-time-point longitudinal study design, adding the acquisition of two time points to the previous two acquisitions of the initial cohort using task-based functional and diffusion tensor (DTI) neuroimaging data, with a new emphasis on how emotional functioning relates to impulsivity. To address the dimensional nature of impulsivity we will also add a group of individuals with subclinical ratings of impulsivity, to explore how the full range and persistence of impulsivity over time affects outcomes. We will now extend the age range from the initial data collection at 12 to 25 years to 15 to 30 years in the previously recruited neurotypicals (NT) and participants with ADHD. We will focus on impulsivity-related outcomes that are more likely to emerge in the 15 to 30-year age span such as irritability, emotional lability, psychiatric and substance use disorders, self-harm and suicide attempts, and academic and occupational dysfunction. We hypothesize that the strength of the structural connectivity between (1) the dorsolateral prefrontal cortex (DLPFC) and dorsal striatum pathway will predict individual differences in impulsivity, with greater negative coupling between the DLPFC and dorsal striatum associated with greater impulse control. We posit that this connection will strengthen with maturity. We also hypothesize that increased connectivity strength between (2) the ventral striatum and the amygdala will predict more impulsive behavior. We aim to characterize in a multi-modal (fMRI, DTI, behavior) longitudinal imaging investigation: (a) how these changes emerge from early adolescence through young adulthood and (b) how these developmental changes are reflected in persons ranging from typical through elevated and significant impulsivity. Furthermore, we will assess how brain connectivity and behavior differ between persons with ADHD who continue to express impulsive decisions (persisters) versus those who are no longer making impulsive decisions (remitters) during the transition into young adulthood. We will also assess how functioning in these neural systems (e.g., DLPFC & striatum) may be moderated by and associated with irritability and degree of emotional regulation. Extending an aim from the original grant, we will test the relation between brain functioning and real-world functioning, including occupational achievement, presence of psychopathology, self-harm, and substance use disorders. We will also assess what factors lead to more resilience. At the conclusion of our study we will identify age-specific targets for decreasing impulsivity and preventing self-harm during a period of heightened vulnerability and opportunity.