ADHD: A Controlled Diffusion Tensor Imaging Study

描述（由申请人提供）：注意力缺陷/多动障碍（ADHD）越来越多地被概念为起源于神经发育，尽管这种改变发展背后的机制可能很复杂。迄今为止，结构磁共振成像（sMRI）研究表明，白质（WM）的细微广泛性体积缺陷是ADHD的一个明确且一致的神经解剖学关联。这些脑白质体积缺陷在从未服用过药物的ADHD患者中最为明显（Castellanos et al., 2002），这表明兴奋剂药物使ADHD患者的白质正常化。PI试图将弥散张量成像（DTI）应用于具有重大公共卫生意义的发育障碍，这是一种检查白质微观结构异常的潜在强大工具。像多动症这样的发育障碍是特别适合使用DTI进行研究的，因为神经精神疾病中大脑结构完整性的变化在宏观结构水平上可能是微妙的，但在微观结构水平上可能更可靠地检测到，从而对多动症白质参与的区域模式有了新的认识。具体目的：本研究的工作假设是ADHD的高级认知和行为功能障碍可能是在白质中产生可检测的解剖病理的神经区域成熟的分布异常的结果。本研究将检验3个主要假设：(a)相对于正常对照（NC）， ADHD儿童在先前的sMRI研究中发现异常的区域（如额皮质、额纹状体和胼胝体）的白质分数各向异性（FA）较低。(b)前额皮质白质分数各向异性的测量将与被认为是由额叶系统提供的某些神经认知测试的表现相关。(c) ADHD患者尾状核体积比正常人小。作为一个探索性目的，我们提出将额叶FA值与ADHD患者的绝对和相对尾状核体积相关联。基于ADHD额纹状体功能障碍的工作假设，我们预测ADHD儿童额下FA值与尾状体体积呈正相关。研究设计与方法：本研究将招募30名未服药的7 - 11岁ADHD儿童和30名性别、年龄、利手性、种族和社会经济地位匹配的NC儿童。每位受试者将接受核磁共振成像，以及认知和行为测试。通过使用感兴趣区域和体素分析，我们将能够首次描述ADHD患者白质完整性受损的特征，这是由扩散张量成像推断出来的。意义：关于白质异常在ADHD中的作用的问题只能在从未用药的患者中得到回答。确认ADHD儿童白质超微结构异常将确立白质发育在ADHD病理生理学中的重要性，并为未来研究兴奋剂药物对白质发育的影响提供基础。

DESCRIPTION (provided by applicant): Attention-Deficit/Hyperactivity Disorder (ADHD) is increasingly being conceptualized as neurodevelopmental in origin although the mechanisms behind such altered development are likely to be complex. To date, structural magnetic resonance imaging (sMRI) studies suggest that subtle generalized volumetric deficits in white matter (WM) are a clear and consistently replicated neuroanatomic correlate of ADHD. These WM volumetric deficits are most pronounced in never-medicated patients with ADHD (Castellanos et al., 2002), suggesting that stimulant medications normalize white matter in patients with ADHD. The PI seeks to apply diffusion tensor imaging (DTI), a potentially powerful tool for examining abnormalities in white matter microstructure, to a developmental disorder of great public health significance. Developmental disorders like ADHD are particularly ripe for investigation using DTI since changes in brain structural integrity in neuropsychiatric conditions which may be subtle on a macrostructural level may be more reliably detected on the microstructural level allowing for new insights into the regional patterns of white matter involvement in ADHD. Specific Aims: The working hypothesis for the present study is that the higher-level cognitive and behavioral functions disordered in ADHD may be the result of distributed abnormalities in the maturation of neural regions that produce detectable anatomic pathology in white matter. This study will test 3 main hypotheses: (a) Relative to normal controls (NC), children with ADHD will have lower white matter fractional anisotropy (FA) in regions where abnormalities have been detected in previous sMRI studies (e.g., fronto-cortical, fronto-striatal and corpus callosum). (b) Measures of prefrontal cortical white matter fractional anisotropy will be correlated with performance on selected neurocognitive tests thought to be subserved by frontal systems. [(c) ADHD patients compared with normals will have smaller caudate volume. As an exploratory aim, we propose to correlate frontal lobe FA values with both absolute and relative caudate volume of ADHD patients. Based on the working hypothesis of frontostriatal malfunction in ADHD, we predict that inferior frontal FA values will be positively correlated with caudate volume in children with ADHD.] Research Design and Methods: This study will recruit 30 never-medicated, 7 to 11 year old children with ADHD and 30 NC children matched on gender, age, handedness, ethnicity and socioeconomic status. Each subject will undergo an MRI, as well as cognitive and behavioral testing. By using both a region-of-interest and voxel-wise analysis, we will be able for the first time to characterize compromised white matter integrity in ADHD, as inferred by diffusion tensor imaging. Significance: Questions about the role of white matter abnormalities in ADHD can only be answered in never-medicated patients. Confirmation of an abnormality in white matter rnicrostructure in children with ADHD would establish the importance of white matter development in the pathophysiology of ADHD and would provide the basis for future studies to prospectively examine the effects of stimulant medications on white: matter development.