NOVEL CORTICAL LIMBIC ANALYSIS IN TWINS DISCORDANT FOR ADHD

描述（由申请人提供）：注意缺陷多动障碍（ADHD）是一种高度遗传的神经发育障碍，假设具有非常早期的发育起源。一些功能和结构的神经影像学研究表明，有相对弥漫性广泛的皮质和皮质下的差异与提高局灶性差异发生在额叶，纹状体和顶叶区域。这项R21提案旨在利用两种新的图像分析方法来表征患有注意力不集中ADHD的青少年和年轻人的大脑皮层，这是一个现有的，独特的多国试点成像数据集，双胞胎不一致，注意力不集中ADHD。我们建议使用基于表面的分析方法来表征与注意力不集中多动症相关的脑沟/脑回折叠模式在整个大脑皮层中的差异，以获得脑沟深度图，最近由货车埃森和同事开发和实施。同时，我们将使用由米勒和同事建立的方法来量化扣带皮层的局部皮层距离度量（LCDM），扣带皮层是一个假设在ADHD中被破坏的区域。表面脑沟深度分析的结果将用于以综合方式识别其他感兴趣区域，以通过LCDM进行研究。因此，本申请提出了几种独特的，前沿的图像分析技术，这些技术以前从未结合用于任何疾病的研究。我们假设这种组合有很强的潜力，大大提高我们对ADHD潜在病理生理学的认识。然而，由于这些方法以前没有应用于ADHD的研究或在任何研究中同时使用，因此认为该项目对于R 01应用来说过于初步。我们试图实现以下三个主要目标：1）表征与注意力不集中ADHD相关的整个皮层脑沟深度测量的差异; 2）量化与注意力不集中ADHD相关的扣带皮层LCDM的差异; 3）在同一人群中通过脑沟度量确定差异的区域中通过LCDM表征区域皮层形态。用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R 01研究。如果获得资助，该项目将是第一个检查和表征ADHD中的皮质折叠异常的项目，也是第一个将联合收割机脑沟深度映射与任何疾病中的局部皮质度量表征相结合的项目。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个强大的机制来表征皮质特征，并将显着推进我们对ADHD和精神疾病的基础病理生理学的理解。据估计，ADHD影响全球5-12%的人口，由于其相关的功能障碍和发病率，对公共卫生产生重大影响。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要的公共卫生问题。ADHD的潜在神经生物学尚未完全了解，本项目旨在了解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.