NOVEL CORTICAL LIMBIC ANALYSIS IN TWINS DISCORDANT FOR ADHD

描述(申请人提供)：注意缺陷多动障碍(ADHD)是一种高度遗传性的神经发育障碍，被认为具有非常早期的发育起源。许多功能和结构神经成像研究表明，皮质和皮质下存在相对广泛的差异，额叶、纹状体和顶叶区域的局灶性差异明显。这份R21提案旨在利用两种新的图像分析方法，在现有的、唯一的多国试点双胞胎成像数据集中，对注意力不集中的ADHD青少年和年轻人的皮质进行表征。我们建议使用基于表面的分析方法来表征整个大脑皮层中与注意力不集中的ADHD相关的脑沟/脑回折叠模式的差异，以得出最近由Van Essen和他的同事开发和实现的脑沟深度图。同时，我们将使用Miller和他的同事建立的方法来量化扣带皮质中的局部皮质距离度量(LCDM)，这是一个假设在ADHD中被破坏的区域。表层沟深度分析的结果将被用来以综合方式确定通过土地利用/清洁发展机制进行调查的其他感兴趣区域。因此，这项申请提出了几种独特的、尖端的图像分析技术，这些技术以前从未被结合起来研究任何疾病。我们推测，这种结合有很大的潜力大大加深我们对ADHD潜在病理生理学的了解。然而，由于这些方法以前没有被应用于ADHD的调查，或者同时用于任何调查，该项目被认为对于R01的应用来说过于初步。我们试图实现以下三个主要目标：1)在整个大脑皮质的脑沟深度测量中表征与疏忽的ADHD相关的差异；2)量化与疏忽的ADHD相关的扣带皮质LCDM的差异；以及3)在同一人群中通过脑沟测量识别差异的区域中，通过LCDM表征区域的皮质形态。通过这些组合方法实现这些目标，将证明联合应用这些技术在ADHD中的可行性和实用性，以便最终进行更大、更明确的R01研究。如果得到资助，这个项目将是第一个检查和描述ADHD患者皮质折叠异常的项目，也是第一个将脑沟深度标测与局部皮质测量特征相结合的项目。我们假设，这两种独特的图像分析方法的结合使用将提供一种强大的机制来表征皮质特征，并将显著促进我们对ADHD和精神障碍的潜在病理生理学的理解。与公共健康相关的ADHD估计影响全球5-12%的人口，由于其相关的功能障碍和发病率对公共健康有重大影响。ADHD的流行及其对个人和家庭功能的普遍影响使其成为一个重大的公共卫生问题。ADHD的潜在神经生物学尚不完全清楚，本项目试图了解ADHD的皮质折叠特征。

DESCRIPTION (provided by applicant): Attention Deficit Hyperactivity Disorder (ADHD) is a highly heritable neurodevelopmental disorder hypothesized to have very early developmental origins. A number of functional and structural neuroimaging studies suggest that there are relatively diffuse widespread cortical and subcortical differences with heightened focal differences occurring in frontal, striatal and parietal regions. This R21 proposal aims to utilize two new image analysis methods to characterize the cortex in adolescents and young adults with inattentive ADHD in an existing, unique multi-national pilot imaging data set of twins discordant for inattentive ADHD. We propose to characterize differences in sulcal/gyral folding patterns associated with inattentive ADHD across the whole cerebral cortex using surface based analysis methods, to derive sulcal depth maps, recently developed and implemented by Van Essen and colleagues. Concurrently we will use methods established by Miller and colleagues to quantify local cortical distance metrics (LCDM) in the cingulate cortex, a region which is hypothesized to be disrupted in ADHD. Results from surface sulcal depth analyses will be used to identify, in an integrated fashion, additional regions of interest to investigate via LCDM. Thus this application proposes several unique, cutting-edge image analysis techniques which have never been previously combined for the study of any disorder. We hypothesize this combination has a strong potential to substantially further our knowledge of the underlying pathophysiology of ADHD. However since these methods have not been applied previously to the investigation of ADHD or used concurrently in any investigation, this project is considered too preliminary for an R01 application. We seek to achieve the following three primary Aims: 1) characterize differences associated with inattentive ADHD in sulcal depth measures across the whole cortex; 2) quantify differences in LCDM of the cingulate cortex associated with inattentive ADHD; and 3) characterize regional cortical morphology by LCDM in regions of identified differences by sulcal metrics in this same population. Achieving these Aims with these combined methods will demonstrate the feasibility and utility of jointly applying these techniques in ADHD in order to eventually pursue a larger more definitive R01 study. If funded this project will be the first to examine and characterize cortical folding abnormalities in ADHD and the first to combine sulcal depth mapping with local cortical metric characterization in any disorder. We hypothesize that the combined use of these two unique image analysis approaches will provide a powerful mechanism to characterize cortical characteristics and will significantly advance our understanding of the underlying pathophysiology of ADHD and psychiatric disorders. PUBLIC HEALTH RELEVANCE ADHD is estimated to affect 5-12% of the population worldwide and because of its associated functional impairment and morbidity has significant public health impact. The prevalence of ADHD and its pervasive influence on individual and family functioning make it a significant public health concern. The underlying neurobiology of ADHD is incompletely understood and this project seeks to understand cortical folding characteristics of ADHD.