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）：尽管这种改变的发展背后的机制可能很复杂，但注意力缺陷/多动症（ADHD）越来越被概念化为神经发育的起源。迄今为止，结构磁共振成像（SMRI）的研究表明，白质（WM）中细微的广义体积缺陷是ADHD的明确且一致地复制的神经解剖学相关性。这些WM体积缺陷在从未服用的ADHD患者中最为明显（Castellanos等，2002），这表明刺激性药物对ADHD患者的白质正常化。 PI试图应用扩散张量成像（DTI），这是一种潜在的强大工具，用于检查白质微观结构异常的功能，以使其具有巨大的公共健康意义的发育障碍。使用DTI这样的发育障碍尤其成熟，因为在神经精神疾病中的大脑结构完整性的变化可能在宏观结构水平上可能很细微，可以在微观结构上更可靠地检测到微观结构水平上，从而可以对ADHD中白质公司的区域介入的区域介入进行新的见解。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障碍可能是由于神经区域成熟的分布异常的结果，这些神经区域的成熟是在白质中产生可检测到的解剖病理学的结果。这项研究将检验3个主要假设：（a）相对于正常对照（NC），患有ADHD的儿童将在先前的SMRI研究中发现异常（例如额叶，额叶，额叶和癌症）中检测到异常的区域中，白质分数各向异性（FA）。 （b）前额叶皮质白质分数各向异性的度量将与所选神经认知测试的性能相关，认为这些神经认知测试被认为是由额叶系统提供的。 [（c）与正常患者相比，ADHD患者的尾状体积较小。作为探索性目的，我们建议将额叶FA值与ADHD患者的绝对和相对尾声相关联。基于ADHD中额叶功能故障的工作假设，我们预测，ADHD儿童的下部FA值将与尾状体积呈正相关。每个受试者将接受MRI，以及认知和行为测试。通过使用利益区域和体素分析，我们将首次能够表征ADHD中的白质完整性，这是通过扩散张量成像所推断的。意义：关于白质异常在ADHD中的作用的问题只能在从未服用的患者中回答。确认多动症儿童中白质rnicrostrouce的异常将确定白质发育在ADHD的病理生理学中的重要性，并将为未来的研究提供基础，以前瞻性研究刺激药物对白人的影响：物质发展：物质发展。