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力缺陷/多动障碍（ADHD）的病理生理学，方法是将与注意力缺失相关的神经回路与受试者内反应时间变异性增加联系起来。基于我们的初步数据，我们假设ADHD相关异常的存在下，在连接背侧前扣带皮层（dACC）的电路的功能连接（区域时间一致性）的压后复合体（RSC;包括后扣带皮层和楔前叶）。我们建议在50名右撇子未服药的成人中描述这种新的功能障碍候选位点，这些成人目前患有ADHD，并且一生都有ADHD的病史，另外还有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。我们将（1）使用fMRI来复制我们的初步研究结果，即ADHD相关的dACC/RSC功能连接强度降低;（2）使用弥散张量成像（DTI）评估dACC/RSC回路结构完整性的组间差异;（3）将回路完整性的功能和结构测量与扫描过程中两项反应任务中的个体内反应时间变异性相关联。我们还将获得一个全面的电池评估几乎所有公认的神经心理缺陷多动症，以探讨受试者内变异，脑回路异常，神经心理缺陷多动症之间的关系。这个建议，结合了新的方法，新的具体假设，大量的初步数据，有可能描绘大脑行为的关系，将告知翻译模型的病理生理学这种常见的和高度损害的疾病。公共卫生相关性：我们建议应用新的神经影像学方法，以更好地了解参与注意力缺陷多动障碍（ADHD）的大脑机制。ADHD患者的反应高度不一致，我们将在50名ADHD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参与ADHD的关键心理能力，包括警觉性，工作记忆，抑制不必要反应的能力，改变心理定势的能力，以及时间短暂间隔的能力。这项研究有可能告诉我们ADHD中特定脑回路的功能和功能障碍，这是一种常见的损害性疾病。需要这些信息来改进诊断方法和开发新的治疗方法。

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.