Project 3

项目3

• 批准号: 7480929
• 负责人: James McCracken
• 金额: $ 22.31万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480929
• 关键词: Adolescent; Adult; Adverse effects; Agonist; Anatomy; Area; Attention deficit hyperactivity disorder; Behavior; Behavior Therapy; Behavioral; Child; Chronic; Clinical; Clinical Research; Cognitive; Cognitive Therapy; Combined Modality Therapy; Comorbidity; Corpus striatum structure; Data; Development; Diagnostic; Disease; Dopamine; Dopamine Agonists; Electroencephalography; Elements; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Gilles de la Tourette syndrome; Guanfacine; Habits; Impairment; Individual; Intervention; Measurement; Measures; Methylphenidate; Neurocognitive; Obsessive-Compulsive Disorder; Parietal; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Prefrontal Cortex; Reaction Time; Recruitment Activity; Research; Research Personnel; Role; Sampling; Severities; Short-Term Memory; Signal Transduction; Subgroup; Symptoms; System; Techniques; Therapeutic Effect; Tic disorder; Training; Treatment Protocols; Week; Work; base; cognitive control; cost; executive function; frontal lobe; improved; interest; nerve supply; neuroimaging; neuropsychiatry; noradrenergic; programs; psychostimulant; relating to nervous system; response; size; training project; treatment effect

A host of evidence from clinical studies and neuroimaging clearly indicates that elements of cognitive control, such as working memory and response inhibition, are diminished in children and adults with attention deficit/hyperactivity disorder. These functions are subserved in part by the fronto-striatal circuits connecting with dorsolateral prefrontal cortex for working memory, and with ventrolateral prefrontal cortex for response inhibition. Because of the known dopaminergic innervation of these areas, and the therapeutic effects of indirect dopaminergic agonists such as psychostimulants for ADHD, there has been interest in the direct role of dopamine in the modulation of the circuits underlying these abilities. Numerous studies have suggested that DA-modulation can yield behavioral improvements in response inhibition and WM performance in ADHD. Furthermore, neuroimaging work using both EEC and fMRI has suggested that DA modulation can result in normalized activity in children with ADHD. Pharmacologic treatment studies also suggest that other manipulations, such as alpha2 agonist exposure, may improve cognitive control. Our proposed studies aim to clarify the functional anatomy of key circuits subserving cognitive control in children and adolescents with ADHD and to compare and contrast hypothesized mechanisms of cognitive enhancement associated with dopaminergic and noradrenergic treatments in isolation or combination. Subjects recruited will undergo fMRI and EEG at Weeks 0, 4, and 8, allowing measurement of the effects of methylphenidate and guanfacine on behavior and neural activity. The primary aims are to determine how neural activity differs between children with ADHD and normal controls on response inhibition (measured using the stop-signal task) and spatial working memory (measured using a spatial Sternberg task) challenges, and how this response is modulated by pharmacotherapies. The project also aims to determine whether EEG and/or fMRI can predict treatment response to different pharmacotherapy regimens. These aims synergize with the larger Center in providing a neuroscientific basis for understanding the effects of treatments for developmental neuropsychiatric disorders.

来自临床研究和神经影像学的大量证据清楚地表明，认知控制的要素， 诸如工作记忆和抑制作用的抑制作用在儿童和成人中受到关注的减少 赤字/多动症障碍。这些功能由连接的额纹状体电路部分提供 带有后外侧前额叶皮层用于工作记忆，并带有腹外侧前额叶皮层以应答 抑制。由于这些区域的已知多巴胺能神经支配，以及 间接多巴胺能激动剂，例如多动症的心理刺激药，对直接作用引起了兴趣 多巴胺在调制这些能力的基础电路中的。许多研究表明 DA调节可以在响应抑制和WM表现中产生行为改善 多动症。此外，使用EEC和fMRI的神经影像学工作表明，DA调制可以 导致ADHD儿童的归一化活性。药物治疗研究还表明其他 操纵（例如α2激动剂暴露）可能会改善认知控制。我们提出的研究目的 为了澄清关键电路的功能解剖结构，使儿童和青少年在 ADHD并比较和对比，假设的认知增强机制 多巴胺能和甲肾上腺素能治疗分离或组合。招募的受试者将在第0、4和8周进行fMRI和EEG，以衡量的效果 关于行为和神经活动的哌醋甲酯和鸟甲酸。主要目的是确定如何 ADHD儿童与反应抑制的正常对照之间的神经活动不同（测量 使用停止信号任务）和空间工作记忆（使用空间Sternberg任务测量） 挑战以及该反应如何通过药物治疗调节。该项目还旨在确定 脑电图和/或fMRI是否可以预测对不同药物治疗方案的治疗反应。这些 目的与更大的中心协同为理解神经科学基础 发育神经精神疾病的治疗方法。