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)的变量有很好的记录，但通常会持续到成年，但人们对成年后潜在的神经相关性知之甚少。ADHD成人的神经成像研究通常包括ADHD儿童的一小部分，他们成年后会向临床医生自我报告症状。因此，对自己的ADHD(一个众所周知的特征)认识有限的成年人，或者没有寻求治疗的成年人(大多数患有儿童期ADHD)，都被排除在这些研究之外。对患有儿童ADHD的成年人的大脑功能进行研究，辅以从童年到成年的附带报告和症状的反复评估，可能有助于提供有关ADHD病理生理学方面的必要信息。现有的成人ADHD研究主要集中在“冷”执行功能(EF)的背侧和外侧前额叶系统的功能上。然而，最近的证据表明，在认知和动机/情绪过程的交界处支持加工的额纹状体边缘系统也可能在ADHD中受损-也被称为“热”EF，涉及行为和情绪的自我调节。这个应用程序建议检查神经系统支持“冷”和“热”EF的功能，与ADHD症状的强大潜在变量增长曲线相关，该曲线是从匹兹堡ADHD纵向研究(PALS)的25岁以上独特频繁的长期评估中估计的。PARTS将由200名年轻人(150名患有儿童ADHD，50名没有儿童ADHD)参加--这是一项正在进行的关于儿童ADHD过程和结果的研究(R37AA11873)。使用fMRI范式，我们将评估神经区域中的神经活动和神经区域之间的功能连接，这些神经区域涉及a)在有奖赏的反眼跳任务中抑制控制的奖赏调制，以及b)在情绪工作记忆任务中对情绪显著信息的干扰控制。重要的是，鉴于最近有证据表明，情绪失调(具体地说，愤怒易怒)可能与ADHD有不同的神经生物学基础，我们将测试上述神经成像指标的变化与愤怒易怒的关联程度--纵向测量也是如此。神经成像指数将被测试为在评估情感决策、冒险和情感反应抑制的任务中，作为症状过程和表现之间关系的调节变量。最后，我们将探索这些奖赏抑制性控制和情绪工作记忆的神经成像指标与a)白质完整性、b)刺激性治疗史和c)自我报告变量(如重向敏感性和积极/消极紧迫感)之间的关系。这项拟议的研究在成人多动症神经成像文献中将是独一无二的，因为它强调了成人中具有良好特征的童年病史前瞻性地跟踪到成年期，随着时间的推移利用潜在特征的独特频繁的重复评估的双重的“冷”和“热”EF系统。综合的大脑行为发现可能会刺激对治疗干预的新靶点的研究，并促进对ADHD病理生理学的理解。

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.