ADHD: A Controlled Diffusion Tensor Imaging Study

ADHD：受控扩散张量成像研究

• 批准号: 7006054
• 负责人: Manzar Ashtari
• 金额: $ 8.06万
• 依托单位: FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-10 至 2006-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7006054
• 关键词: attention deficit disorder; behavior test; behavioral /social science research tag; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain morphology; caudate nucleus; child (0-11); clinical research; corpus callosums; diffusion magnetic resonance imaging; frontal lobe /cortex; human subject; neuropsychological tests; pathologic process; white matter

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.

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，尽管这种改变发展背后的机制可能很复杂。到目前为止，结构磁共振成像(SMRI)研究表明，细微的全身性白质体积缺陷(WM)是ADHD明确且一致复制的神经解剖学相关性。这些WM体积缺陷在从未服用药物的ADHD患者中最为明显(Castellanos等人，2002年)，这表明兴奋剂药物使ADHD患者的脑白质正常化。PI试图将扩散张量成像(DTI)应用于一种对公共卫生具有重大意义的发育障碍，这是一种潜在的检查白质微结构异常的强大工具。像ADHD这样的发育障碍尤其适合使用DTI进行研究，因为在神经精神疾病中，大脑结构完整性的变化在宏观结构水平上可能是微妙的，可能在微观结构水平上更可靠地被检测到，从而允许对ADHD涉及白质的区域模式有新的见解。具体目的：本研究的工作假设是，ADHD患者较高水平的认知和行为功能障碍可能是神经区域成熟的分布式异常的结果，这些异常在白质中产生了可检测到的解剖病理。本研究将检验3个主要假说：(A)与正常对照组(NC)相比，ADHD儿童在先前sMRI研究中发现异常的区域(如额叶皮质、额叶纹状体和穹隆体区)的白质分数各向异性(FA)较低。(B)前额叶皮质白质各向异性分数的测量将与选定的神经认知测试的表现相关，这些测试被认为是额叶系统的辅助。[(C)ADHD患者与正常人相比，尾状核体积较小。作为一个探索性目标，我们建议将额叶FA值与ADHD患者的绝对尾状体积和相对尾状体积相关联。根据ADHD额纹状体功能障碍的工作假说，我们预测ADHD儿童额叶下部FA值与尾状核体积呈正相关。]研究设计和方法：本研究将招募30名未服用药物的7-11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正常儿童。每个受试者都将接受核磁共振检查，以及认知和行为测试。通过使用感兴趣区和体素分析，我们将第一次能够通过扩散张量成像来表征ADHD患者白质完整性受损的特征。意义：关于脑白质异常在ADHD中的作用的问题只能在从未服药的患者中得到回答。ADHD儿童脑白质微结构异常的证实将确立脑白质发育在ADHD病理生理学中的重要性，并将为未来前瞻性研究兴奋剂对脑白质发育的影响提供基础。