Multiple pathway models of attention deficit hyperactivity disorder (ADHD)

项目摘要/摘要本资助的目的是研究注意缺陷多动障碍（ADHD）儿童以及对照组和ADHD儿童在执行功能和奖励处理过程中的大脑差异。我们将对8- 9岁患有混合型多动症的男孩进行药物治疗，因为研究表明，药物、年龄相关、性别和亚型对多动症的行为表现和大脑激活有影响。反应抑制是通过一个去不去的任务来衡量的，它将被用来衡量执行功能，因为这种认知过程可能是多动症儿童中最常见的缺陷。执行功能任务将在即时和延迟强化条件下进行，因为研究表明ADHD儿童可能具有不同的延迟强化梯度。这项资助的中心目标是确定ADHD儿童潜在的大脑异常是否以二分类或连续行为分布为特征。如果大脑异常表现为二分类行为分布（即缺陷与无缺陷），我们预计ADHD儿童的一部分大脑异常局限于执行功能回路（包括腹侧前额叶皮层和背侧纹状体），而ADHD儿童的一部分大脑异常局限于奖励处理回路（包括眶额叶皮层和腹侧纹状体）。我们进一步预计，ADHD儿童的一部分在这两个领域都有行为缺陷，他们可能在这两个回路中都有特别明显的大脑异常。尽管对多动症合并型的有限行为研究表明，大致相等数量的儿童属于这些神经心理学定义的类别，但执行功能和奖励处理能力可能存在更连续的行为分布。为了检验这一假设，我们将使用多元回归直接比较二分类模型和连续模型。如果二分行为模型不能解释大脑异常，但连续模型可以，那么我们可以得出结论，潜在的缺陷具有连续分布的特征。如果两种模型都能解释方差，但连续模型比二分类模型能解释更多的方差，那么我们可以得出结论，潜在赤字既有连续成分，也有二分类成分。我们还将使用动态因果模型（DCM）进行探索性分析，以检查这些电路中感兴趣的区域之间的有效连接模式。公共卫生相关性：相关性没有研究检查ADHD亚型的神经相关性，这些亚型是基于神经心理学上的行为定义的，因此这项资助的结果将对ADHD儿童亚型的客观诊断产生影响。这项资助可能会导致进一步的研究，以检验医疗干预对ADHD亚型中执行功能和奖励处理的神经相关性的影响。

DESCRIPTION (provided by applicant): Multiple pathway models of attention deficit hyperactivity disorder (ADHD) Project Summary/Abstract The goal of this grant is to examine brain differences during executive functioning and reward processing among children with attention deficit hyperactivity disorder (ADHD) and between control and ADHD children. We will examine medication naove 8- to 9-year- olds boys with the combined type of ADHD, because research has shown medication, age-related, sex and subtype effects in ADHD in terms of behavioral performance and brain activation. Response inhibition as measured by a go no-go task will be used to index executive functioning because this cognitive process may be the most common deficit in ADHD children. The executive functioning task will be given under immediate and delayed reinforcement conditions because studies have suggested that ADHD children may have a different delay-of-reinforcement gradient. The central goal of this grant is to determine if the underlying brain abnormalities in ADHD children are characterized by a dichotomous or continuous behavioral distribution. If brain abnormalities are characterized by a dichotomous behavioral distribution (i.e. deficit versus no deficit), we expect that a subset ADHD children will have brain abnormalities restricted to the executive functioning circuit (including ventro-lateral prefrontal cortex and dorsal striatum) and a subset of ADHD children will have brain abnormalities restricted to the reward processing circuit (including orbito-frontal cortex and ventral striatum). We further expect that a subset of ADHD children will have a behavioral deficit in both domains and they may have especially pronounced brain abnormalities in both circuits. Although limited behavioral research on the ADHD combined type suggests that approximately equal numbers of children fall into these neuropsychologically-defined categories, it is possible that there is a more continuous behavioral distribution of executive functioning and reward processing ability. In order to test this hypothesis, we will directly compare a dichotomous to a continuous model using multiple regression. If the dichotomous behavioral model does not explain brain abnormalities, but the continuous model does, then we can conclude that the underlying deficit is characterized by a continuous distribution. If both models explain variance, but the continuous model explains significantly more variance than the dichotomous model, then we can conclude that the underlying deficit has both a continuous and dichotomous component. We will also perform exploratory analyses using Dynamic Causal Modeling (DCM) to examine patterns of effective connectivity between regions of interest in these circuits. PUBLIC HEALTH RELEVANCE: Relevance No studies have examined the neural correlates of ADHD subtypes that have been neuropsychologically-defined based on their behavior, so the results of this grant will have implications for the objective diagnosis of subtypes of ADHD children. This grant will potentially lead to further studies that examine the effect of medical intervention on the neural correlates of executive functioning and reward processing in ADHD subtypes.