Neurology of Deficient Response Control in ADHD

描述（由申请人提供）：注意力缺陷/多动障碍（ADHD）是一种高度流行的疾病，其中对不想要的行为的控制受损会影响家庭/社会关系和学校表现。由基底神经节和皮层水平的辅助运动区（SMA）介导的运动反应控制对于选择抑制不需要的反应至关重要，因此对于有效抑制以ADHD为特征的冲动，多动和任务外行为是必要的。最初授权期的研究结果表明，ADHD与运动反应控制异常相关，包括反应抑制受损和受试者内反应变异性（ISV）增加;此外，在具有不同认知需求的任务中，这些指标的受损程度相似，这表明运动反应控制受损是ADHD的主要缺陷。与这些行为观察一致，功能和解剖MRI研究显示ADHD儿童在SMA和基底神经节的相互连接区域显示异常。大脑行为相关性的功能性MRI检查提供了进一步的见解，揭示了ADHD儿童，但不是典型发育（TD）儿童，前额叶皮层的招募与较低的ISV相关，反映了反应控制的改善。结合行为和成像的结果提供了一个基础，转向一个更发展的模型ADHD，其中功能障碍的神经系统的关键运动反应控制，建立在发展的早期，有助于疾病的病理生理学，而后期发展的前额叶系统的功能促进补偿。本提案的目标是：使用新的成像方法来研究涉及SMA和基底神经节的神经回路异常导致ADHD相关的反应控制障碍的假设（目的1），研究某些ADHD儿童成功的运动反应控制取决于前额叶的募集的假设。（而不是典型的运动前）电路（目标2和3），并调查是否呈现格式，提高警觉也可以导致改善反应控制（目标4）。拟议的研究不仅有助于确定ADHD的相关中间内在表型，而且可能指向潜在有效的治疗策略。公共卫生相关性：注意力缺陷多动障碍（ADHD）是儿童时期的一种常见疾病，其中反应控制问题会影响社交关系和学校表现。这项研究的目的是确定大脑结构的差异，有助于ADHD相关的反应控制障碍，并确定帮助ADHD儿童提高任务表现的机制。这项工作可能有助于改善ADHD的诊断和治疗。

DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD) is a highly prevalent disorder in which impaired control of unwanted behavior affects family/social relationships and school performance. Motor response control, mediated by the basal ganglia and, at the cortical level, the supplementary motor area (SMA), is crucial for selecting to withhold unwanted responses and thereby necessary for effective inhibition of impulsive, hyperactive and off-task behavior that characterizes ADHD. Findings from the initial grant period established that ADHD is associated with abnormalities in motor response control, including impaired response inhibition and increased intrasubject response variability (ISV); additionally, the degree of impairment on these measures was found to be similar across tasks with differing cognitive demands, suggesting that impaired motor response control is a primary deficit in ADHD. Consistent with these behavioral observations, functional and anatomic MRI studies reveal children with ADHD show abnormalities in the SMA and interconnected regions of the basal ganglia. Functional MRI examination of brain-behavior correlations provided further insight, revealing that for children with ADHD, but not typically developing (TD) children, recruitment of the prefrontal cortex was associated with lower ISV, reflecting improved response control. The combined behavior and imaging findings provide the basis for a shift towards a more developmental model of ADHD in which dysfunction in neural systems critical to motor response control, established early in development, contributes to the pathophysiology of the disorder, while function of later-developing prefrontal systems facilitates compensation. The goals of the current proposal are to: use novel imaging methods to investigate the hypothesis that abnormalities in a neural circuit involving the SMA and basal ganglia contribute to ADHD-associated impairments in response control (Aim 1), investigate the hypothesis that successful motor response control in some children with ADHD depends on recruitment of prefrontal (rather than typical premotor) circuits (Aims 2 and 3), and investigate whether a presentation format that increases vigilance can also result in improved response control (Aim 4). The proposed studies will not only help to identify relevant intermediate endophenotypes of ADHD but also might point to potentially effective treatment strategies. PUBLIC HEALTH RELEVANCE: Attention Deficit Hyperactivity Disorder (ADHD) is a common disorder in childhood in which problems with response control affect social relationships and school performance. The purpose of this research is to identify differences in brain structure contributing to ADHD-associated impairments in response control and to identify mechanisms that help children with ADHD improve task performance. This work may help to improve diagnosis and treatment of ADHD.