Neural correlates of adult outcomes of childhood ADHD: Affect, reward and control

描述（由申请人提供）：尽管注意缺陷/多动障碍（ADHD）在成年期的病程变化多样，但通常持续存在，但对成年期结果的潜在神经相关性知之甚少。ADHD成人的神经影像学研究通常包括ADHD儿童的一小部分，这些儿童成年后向临床医生自我报告症状。因此，对自己的注意力缺陷多动症（一种众所周知的特征）了解有限的成年人，或未能寻求治疗的成年人（大多数患有儿童注意力缺陷多动症），被排除在这些研究之外。一项对儿童期ADHD患者的脑功能的研究，以及对儿童期到成年期症状的间接报告和反复评估，可能会为ADHD的病理生理学提供所需的信息。现有的关于成人多动症的研究通常集中在背侧和外侧前额叶系统的功能上——这是“酷”执行功能（EF）的基础。然而，最近的证据表明，支持认知和动机/情绪过程界面处理的额纹状体边缘系统（也被称为“热”EF，涉及行为和情绪的自我调节）也可能在ADHD中受损。本申请旨在检验支持“冷”和“热”EF的神经系统的功能与ADHD症状的强大潜在变量增长曲线的关系，这些曲线是根据匹兹堡ADHD纵向研究（PALS）的25岁以上的独特频繁的长期评估估计的。参与者将是来自PALS的200名年轻人（150名患有儿童多动症，50名没有儿童多动症），PALS是一项正在进行的关于儿童多动症的过程和结果的研究（R37AA11873）。利用fMRI范式，我们将评估涉及a)奖励反扫视任务中抑制控制的奖励调节和b)情绪工作记忆任务中情绪显著信息的干扰控制的神经区域的神经活动和功能连接。重要的是，鉴于最近的证据表明情绪失调（特别是愤怒-易怒）可能在ADHD中有不同的神经生物学基础，我们将测试上述神经影像学指标的变化与愤怒-易怒相关的程度，并进行纵向测量。在评估情感决策、风险承担和情感反应抑制的任务中，新成像指数将被测试作为症状病程与表现之间关系的调节因子。最后，我们将探讨奖励性抑制控制和情绪工作记忆这些神经成像指标与a)白质完整性，b)兴奋剂治疗史以及c)自我报告变量（如奖励敏感性和积极/消极紧迫性）之间的关系。这项研究在成人ADHD神经衰老文献中是独一无二的，因为它强调了具有良好童年历史的成年人的双重“冷”和“热”EF系统，并通过独特的频繁重复评估，随着时间的推移挖掘潜在的特征。综合脑行为的发现可能会刺激新的治疗干预目标的研究，并促进对ADHD病理生理的理解。

DESCRIPTION (provided by applicant): Despite the well-documented variable but often persisting course of Attention-Deficit/Hyperactivity Disorder (ADHD) into adulthood, little is known about underlying neural correlates of adulthood outcome. Neuroimaging studies of ADHD adults typically include small subsets of ADHD children who, as adults, self-report symptoms to clinicians. Thus, adults with limited insight into their ADHD (a well-known characteristic), or adults who fail to seek treatment (the majority with childhood ADHD), are excluded from these studies. A study of brain function in adults with well-characterized childhood ADHD, with collateral reports and repeated assessment of symp- toms from childhood into adulthood, may contribute needed information about the pathophysiology of ADHD. Existing studies of adult ADHD have typically focused on the functioning of dorsal and lateral prefrontal sys- tems underlying "cool" executive functions (EF). However, recent evidence suggests that fronto-striatal-limbic systems supporting processing at the interface of cognition and motivational/emotional processes - also known as "hot" EF and implicated in self-regulation of behavior and emotion - may also be impaired in ADHD. This application proposes to examine the functioning of neural systems supporting both "cool" and "hot" EF in relation to powerful latent variable growth curves of ADHD symptoms estimated from the uniquely frequent long-term assessments reaching beyond age 25 of the Pittsburgh ADHD Longitudinal Study (PALS). Partici- pants will be 200 young adults (150 with, and 50 without, childhood ADHD) from the PALS -- an ongoing study (R37AA11873) of the course and outcomes of childhood ADHD. Using fMRI paradigms, we will assess neural activity in, and functional connectivity between, neural regions implicated in a) reward modulation of inhibitory control during a rewarded antisaccade task and b) interference control of emotionally salient information during an emotional working memory task. Importantly, given recent evidence that emotional dysregulation (specifical- ly, anger-irritability) may have distinct neurobiological substrates in ADHD, we will test the extent to which vari- ation in the above neuroimaging indices is associated with anger-irritability also measured longitudinally. Neu- roimaging indices will be tested as moderators of the relations between symptom course and performance on tasks assessing affective decision making, risk taking, and affective response inhibition. Finally, we will explore associations between these neuroimaging indices of rewarded inhibitory control and emotional working memory and a) white matter integrity, b) stimulant treatment history, and c) self-reported variables such as re- ward sensitivity and positive/negative urgency. The proposed study will be unique in the adult ADHD neuroim- aging literature due to its emphasis on the dual "cool" and "hot" EF systems in adults with well-characterized childhood histories prospectively tracked into adulthood with uniquely frequent repeated assessments tapping underlying traits over time. The integrated brain-behavior findings may stimulate research on new targets for therapeutic interventions and advance understanding of ADHD pathophysiology.