Functional and Structural Connectivity in Adult Attention Deficit Hyperactivity D

描述（由申请人提供）：我们提出了一种新的方法来理解注意缺陷/多动障碍（ADHD）的病理生理学，通过将与注意力缺失相关的神经回路与增加的受试者内部反应时间变异性联系起来。根据我们的初步数据，我们假设在连接背前扣带皮层（dACC）和脾后复合体（RSC，包括后扣带皮层和楔前叶）的回路中存在与adhd相关的功能连接异常（区域时间一致性）。我们拟在50名患有ADHD且终生有混合型ADHD病史的右撇子成人样本和50名性别、年龄、智商、社会经济地位和惯用手匹配的健康对照中，对这一新的候选功能障碍位点进行表征。我们将(1)使用fMRI来重复我们关于adhd相关的dACC/RSC功能连接强度下降的初步发现；(2)利用弥散张量成像（DTI）评估各组dACC/RSC回路结构完整性的差异；(3)在扫描期间的两个反应任务中，将回路完整性的功能和结构测量与个体内部反应时间变异联系起来。我们还将获得一个全面的评估几乎所有假定的ADHD神经心理缺陷的系统，以探索受试者内部变异性、脑回路异常和ADHD神经心理缺陷之间的关系。该建议结合了新颖的方法、新颖的特定假设和大量的初步数据，有可能描述大脑-行为关系，这将为这种常见和高度损害的疾病的病理生理学的翻译模型提供信息。公共卫生相关性：我们建议应用新的神经影像学方法来更好地理解涉及注意缺陷/多动障碍（ADHD）的大脑机制。患有多动症的个体在他们的反应中是高度不一致的，我们将在50名患有多动症的成年人和50名健康受试者中研究与这种不一致相关的大脑回路。我们还将测量被怀疑与多动症有关的关键心理能力，包括警觉性、工作记忆、抑制不想要的反应的能力、转移心理状态的能力以及对短时间间隔进行计时的能力。这项提议的研究有可能告诉我们多动症的特定大脑回路的功能和功能障碍，这是一种常见的损害性疾病。这些信息对于改进诊断方法和开发新的治疗方法是必要的。

DESCRIPTION (provided by applicant): We propose a novel approach to understanding the pathophysiology of Attention- Deficit/Hyperactivity Disorder (ADHD) by linking a neural circuit associated with attentional lapses to increased intra-subject response time variability. Based on our preliminary data, we hypothesize the presence of ADHD-related abnormalities in functional connectivity (regional temporal coherence) in a circuit linking dorsal anterior cingulate cortex (dACC) to the retrosplenial complex (RSC; comprising posterior cingulate cortex and precuneus). We propose to characterize this novel candidate locus of dysfunction in a sample of 50 right-handed unmedicated adults with current ADHD and a lifetime history of combined-type ADHD and 50 sex-, age-, IQ-, socioeconomic status-, and handedness-matched healthy comparisons. We will (1) use fMRI to replicate our preliminary findings of ADHD-related decreases in dACC/RSC functional connectivity strength; (2) assess group differences in the structural integrity of the dACC/RSC circuit using diffusion tensor imaging (DTI), and (3) relate functional and structural measures of circuit integrity to intra-individual response time variability during two response tasks during scanning. We will also obtain a comprehensive battery assessing nearly all putative neuropsychological deficits in ADHD in order to explore the relationships between intra-subject variability, brain circuitry abnormalities, and neuropsychological deficits in ADHD. This proposal, which combines novel methods, novel specific hypotheses, and substantial preliminary data, has the potential to delineate brain-behavior relationships that will inform translational models of pathophysiology of this common and highly impairing disorder. PUBLIC HEALTH RELEVANCE: We propose to apply novel neuroimaging methods to better understand the brain mechanisms involved in Attention-Deficit/Hyperactivity Disorder (ADHD). Individuals with ADHD are highly inconsistent in their responses, and we will study a brain circuit that is associated with such inconsistency in 50 adults with ADHD and 50 healthy subjects. We will also measure key mental abilities that are suspected of being involved in ADHD, including alertness, working memory, ability to suppress unwanted responses, ability to shift mental set, and ability to time brief intervals. The proposed study has the potential to teach us about function and dysfunction of specific brain circuits in ADHD, a common and impairing condition. This information is needed to improve methods of diagnosis and to develop new treatments.