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

描述（由申请人提供）：尽管注意力缺陷/多动障碍（ADHD）的变量有据可查，但通常持续到成年期，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儿童的小子集，这些儿童作为成年人向临床医生自我报告症状。因此，对ADHD（一个众所周知的特征）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ADHD），被排除在这些研究之外。对具有明确特征的儿童期ADHD的成人进行脑功能研究，从儿童期到成年期进行附带报告和反复评估症状，可能有助于提供有关ADHD病理生理学的必要信息。现有的成人ADHD研究通常集中在背侧和外侧前额叶系统的功能，潜在的“冷静”执行功能（EF）。然而，最近的证据表明，额-纹状体-边缘系统支持在认知和动机/情绪过程的界面处的处理-也被称为“热”EF，并涉及行为和情绪的自我调节-也可能在ADHD中受损。本申请提出检查支持“冷”和“热”EF的神经系统的功能，其与从匹兹堡ADHD纵向研究（帕尔斯）的达到25岁以上的独特频繁的长期评估估计的ADHD症状的强大潜在变量增长曲线有关。参与者将是来自帕尔斯的200名年轻人（150名患有儿童多动症，50名没有儿童多动症）--这是一项正在进行的儿童多动症病程和结局的研究（R37 AA 11873）。使用功能磁共振成像的范例，我们将评估神经活动，功能连接，涉及的神经区域a）奖励的抑制性控制在一个奖励的反跳任务和B）干扰控制的情绪显着信息在情绪工作记忆任务。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中具有不同的神经生物学底物，我们将测试上述神经影像学指标的变化与纵向测量的愤怒-易怒相关的程度。神经成像指数将作为症状过程与评估情感决策、风险承担和情感反应抑制的任务表现之间关系的调节因子进行测试。最后，我们将探讨这些奖励抑制控制和情绪工作记忆的神经影像学指标与a）白色物质完整性，B）兴奋剂治疗史和c）自我报告变量（如奖励敏感性和积极/消极紧迫感）之间的关联。该拟定研究在成人ADHD神经影像学文献中是独一无二的，因为其强调了具有良好特征的童年史的成人的双重“冷”和“热”EF系统，前瞻性地跟踪到成年期，并随着时间的推移进行独特频繁的重复评估，挖掘潜在特征。整合的大脑行为研究结果可能会刺激对治疗干预新靶点的研究，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.