Inhibitory control and clinical response in ADHD

描述（由申请人提供）：尽管对ADHD的基本认知和动机过程的研究有很长的历史，对ADHD有效治疗的研究也有很长的历史，但几乎完全缺乏有关临床干预影响的基本过程的研究。当代ADHD理论强调一系列基本的认知过程，包括抑制控制、工作记忆和持续注意力，以及基本的动机过程，如延迟相关的冲动（倾向于选择小的、即时的奖励而不是大的、延迟的奖励）。这些模型的一个重要但未经检验的推论是，多动症的主要治疗方法——兴奋剂，如哌醋甲酯（MPH）、行为治疗及其组合——通过改善这些基本过程来发挥作用。因此，我们对这些基本过程对每一种治疗的敏感程度的理解存在重要差距，并且几乎没有数据来说明基本认知和动机过程的变化是否实际上解释了临床环境中的治疗效果。拟议的研究填补了这些空白。首先，这是第一个同时研究MPH和基于绩效的动机激励（即金钱奖励，类似于行为治疗）对ADHD儿童抑制控制、工作记忆、持续注意力和延迟相关冲动的实验室测量的影响的研究（n=108）。一组年龄和性别匹配的对照组（n=108）被纳入比较，但没有给出MPH。我们假设ADHD儿童在缺乏动机激励的情况下会表现出受损的表现，但这种模式在有良好表现的激励的情况下会得到改善。其次，在患有多动症的儿童中，激励将与延长释放的MPH剂量交叉使用（安慰剂，0.3）。（和0.6 mg/kg）在受试者内部的基础上，提供这些模拟治疗对神经认知加工的单独和相互作用的初步检查。第三，拟议的研究将是第一个测试在实验室中评估的MPH对基本过程的影响实际上介导或解释临床对MPH反应的个体差异的程度。为了实现这一目标，ADHD参与者将接受为期3周的双盲学校药物评估，以检查自然环境下MPH对ADHD儿童功能的影响。因此，拟议的研究将在ADHD的基础和临床研究之间架起桥梁，并将为基本认知和动机过程的变化是ADHD治疗工作机制的假设提供关键的初步测试。这项工作将为多动症的新一代转化研究和理论铺平道路。

DESCRIPTION (provided by applicant): Although there is a long history of research on basic cognitive and motivational processes in ADHD and a long history of research on effective treatments for ADHD, there is almost a total absence of research relating basic processes to the impact of clinical interventions. Contemporary theories of ADHD emphasize a range of basic cognitive processes, including inhibitory control, working memory, and sustained attention, and basic motivational processes such as delay-related impulsivity (a tendency to choose small, immediate rewards over larger, delayed rewards). An important, yet untested, corollary of these models is that the primary treatments for ADHD - stimulants such as methylphenidate (MPH), behavioral treatment, and their combination - exert their effects by improving these basic processes. Thus, there are important gaps in our understanding of the extent to which the basic processes are sensitive to each of these treatments, and there are almost no data to address whether changes in basic cognitive and motivational processes actually account for treatment effects in clinical settings. The proposed research fills these gaps. First, it is the first study to concurrently examine the effects of both MPH and performance-based motivational incentives (i.e., monetary rewards, an analogue of behavioral treatment) on laboratory measures of inhibitory control, working memory, sustained attention, and delay-related impulsivity in children with ADHD (n=108). A group of age- and gender-matched controls (n=108) is included for comparison but not given MPH. We hypothesize that children with ADHD will exhibit impaired performance in the absence of motivational incentives, but that this pattern will be ameliorated in the presence of incentives for good performance. Second, among the children with ADHD, incentive will be crossed with doses of extended-release MPH (placebo, O.3., and 0.6 mg/kg) on a within-subjects basis to provide an initial examination of the separate and interactive effects of these analogue treatments on neurocognitive processing. Third, the proposed research will be the first to test the extent to which MPH effects on basic processes assessed in the lab actually mediate, or account for, individual differences in clinical response to MPH. To accomplish this aim, the participants with ADHD will undergo a 3-week, double blind school-based medication assessment to examine MPH effects on ADHD children's functioning in a natural setting. Thus, the proposed research will bridge basic and clinical research in ADHD and will provide critical initial tests of the hypothesis that changes in basic cognitive and motivational processes are the mechanisms by which treatments for ADHD work. This work will pave the way for a new generation of translational research and theory in ADHD.