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）越来越多地被概念化为神经发育起源，尽管这种改变发育背后的机制可能是复杂的。迄今为止，结构磁共振成像（sMRI）的研究表明，微妙的广义体积赤字在白色物质（WM）是一个明确的和一致的复制神经解剖学相关的多动症。这些WM体积缺陷在从未用药的ADHD患者中最明显（Castellanos等人，2002），表明兴奋剂药物使ADHD患者的白色物质正常化。PI旨在将扩散张量成像（DTI）（一种检查白色物质微观结构异常的潜在有力工具）应用于具有重大公共卫生意义的发育障碍。像ADHD这样的发育障碍是特别成熟的调查使用DTI，因为在神经精神疾病的大脑结构完整性的变化，这可能是微妙的宏观结构水平上可能会更可靠地检测到微观结构水平上，允许新的见解的区域模式的白色物质参与ADHD。具体目标：本研究的工作假设是，ADHD患者的高级认知和行为功能障碍可能是神经区域成熟中的分布异常的结果，这些异常在白色物质中产生可检测的解剖病理学。本研究将测试3个主要假设：（a）相对于正常对照（NC），ADHD儿童在先前sMRI研究中检测到异常的区域（例如，额皮质、额纹状体和胼胝体）。(b)前额叶皮质白色物质部分各向异性的测量将与被认为是由额叶系统辅助的选定神经认知测试的表现相关。[(c)ADHD患者与正常人相比，尾状核体积较小。作为一个探索性的目标，我们建议相关的额叶FA值与绝对和相对尾状核体积的ADHD患者。基于ADHD中额纹状体功能障碍的工作假设，我们预测ADHD儿童的下额叶FA值将与尾状核体积呈正相关。研究设计和方法：这项研究将招募30名从未接受过药物治疗的7至11岁ADHD儿童和30名在性别、年龄、利手、种族和社会经济地位方面匹配的NC儿童。每个受试者都将接受MRI以及认知和行为测试。通过使用感兴趣区域和体素分析，我们将能够第一次描述ADHD中受损的白色物质完整性，如扩散张量成像所推断的。意义：关于白色物质异常在ADHD中的作用的问题只能在从未接受过药物治疗的患者中得到回答。ADHD儿童白色物质微结构异常的确认将确立白色物质发育在ADHD病理生理学中的重要性，并将为未来前瞻性研究兴奋剂药物对白色物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.