ADHD: A Controlled Diffusion Tensor Imaging Study

ADHD：受控扩散张量成像研究

• 批准号: 6874037
• 负责人: Manzar Ashtari
• 金额: $ 8.25万
• 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/6874037
• 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，尽管这种改变发育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) 中微妙的普遍体积缺陷与 ADHD 存在明显且一致的神经解剖学相关性。这些白质体积缺陷在从未接受过药物治疗的 ADHD 患者中最为明显（Castellanos 等人，2002），这表明兴奋剂药物可以使 ADHD 患者的白质正常化。该 PI 寻求将弥散张量成像 (DTI) 应用到具有重大公共健康意义的发育障碍中，DTI 是一种用于检查白质微结构异常的潜在强大工具。像 ADHD 这样的发育障碍使用 DTI 进行研究尤其成熟，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很微妙）可能在微观结构水平上更可靠地检测到，从而对 ADHD 中白质参与的区域模式有新的见解。具体目的：本研究的工作假设是，ADHD 中的高级认知和行为功能紊乱可能是神经区域成熟分布异常的结果，这些神经区域在白质中产生可检测的解剖病理学。这项研究将检验 3 个主要假设：(a) 相对于正常对照 (NC)，ADHD 儿童在先前 sMRI 研究中检测到异常的区域（例如额叶皮质、额纹状体和胼胝体）的白质各向异性分数 (FA) 较低。 (b) 前额皮质白质分数各向异性的测量将与被认为受额叶系统促进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。作为一个探索性目标，我们建议将 ADHD 患者的额叶 FA 值与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，我们预测额下叶 FA 值将与 ADHD 儿童的尾状核体积呈正相关。] 研究设计和方法：本研究将招募 30 名从未接受药物治疗的 7 至 11 岁 ADHD 儿童和 30 名在性别、年龄、利手习惯、种族和社会经济地位上匹配的 NC 儿童。每个受试者都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，我们将首次能够描述 ADHD 中白质完整性受损的特征，正如扩散张量成像所推断的那样。意义：关于白质异常在多动症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。确认 ADHD 儿童白质微结构异常将确立白质发育在 ADHD 病理生理学中的重要性，并为未来前瞻性研究兴奋剂药物对白质发育影响的研究奠定基础。