Neurology of Deficient Response Control in ADHD

ADHD 反应控制缺陷的神经病学

• 批准号: 7911612
• 负责人: Stewart H Mostofsky
• 金额: $ 59.78万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7911612
• 关键词: Adolescence; Adult; Affect; Anatomy; Anisotropy; Area; Atlases; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior; Behavioral; Biological; Brain; Child; Childhood; Clinical; Cognitive; Complex; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Disease; Dissociation; Failure; Family; Financial compensation; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Grant; Image; Image Analysis; Impairment; Individual; Laboratories; Lesion; Magnetic Resonance Imaging; Measures; Medial; Mediating; Methods; Modeling; Motor; Neurologic; Neurology; Pattern; Performance; Prefrontal Cortex; Research; Schools; Shapes; Short-Term Memory; Signal Transduction; Stimulus; Structure; System; Task Performances; Testing; Thick; Work; base; behavior observation; brain behavior; effective therapy; endophenotype; imaging modality; improved; insight; morphometry; neural circuit; neuroimaging; neuromechanism; novel; public health relevance; relating to nervous system; response; social; stimulus interval; treatment strategy; vigilance; white matter

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.

描述（由申请人提供）：注意力缺陷/多动症（ADHD）是一种高度普遍的疾病，在这种障碍中，对不良行为的控制受损会影响家庭/社会关系和学校表现。由基底神经节介导的运动响应控制，在皮质水平上介导的补充运动区域（SMA）对于选择扣留不需要的反应至关重要，因此有效地抑制了表征ADHD的脉冲，超动和外态行为。最初赠款期的发现表明，多动症与运动反应控制中的异常相关，包括受损的响应抑制和增加的受试者内反应变异性（ISV）；此外，发现这些措施的损害程度在认知需求不同的任务中相似，这表明运动反应控制受损是多动症中的主要赤字。与这些行为观察一致，功能和解剖学MRI研究表明，ADHD的儿童在基底神经节的SMA和相互联系的区域中表现出异常。对脑行为相关性的功能性MRI检查提供了进一步的见解，表明对于患有多动症但通常不发育的儿童（TD）儿童，募集前额叶皮层与下ISV的募集有关，反映了改善的反应控制。联合行为和成像发现为转向多动症的发展模型提供了基础，在该模型中，在发育早期建立的对运动反应控制至关重要的神经系统中的功能障碍有助于该疾病的病理生理学，同时，随后发展的前偏发系统的功能促进了补偿。当前建议的目标是：使用新型的成像方法来研究以下假说：涉及SMA和基础神经节的神经回路的异常有助于响应控制中与ADHD相关的损害（AIM 1），调查了以下假说：某些儿童在某些儿童中的成功运动响应依赖于典型的前期及3循环（而不是典型的frentical tigitive and tripical tigitive and tripical of Airpial and tim civid）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）（是否循环）。提高警惕性的演示格式也可以改善响应控制（AIM 4）。拟议的研究不仅将有助于鉴定多动症的相关中间性内表型，而且可能指出了潜在的有效治疗策略。公共卫生相关性：注意力缺陷多动症（ADHD）是童年时期一种常见的疾病，其中反应控制问题会影响社会关系和学校表现。这项研究的目的是确定大脑结构的差异，导致响应控制中与ADHD相关的障碍，并确定帮助患有多动症儿童改善任务绩效的机制。这项工作可能有助于改善多动症的诊断和治疗。