STRUCTURAL AND SPECTROSCOPIC BRAIN MRI IN AUTISM

自闭症患者的结构和能谱脑 MRI

• 批准号: 6108884
• 负责人: MICHAEL E. BRANDT
• 金额: $ 16.82万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6108884
• 关键词: Macaca mulatta; adolescence (12-20); amygdala; aspartate; autism; bioimaging /biomedical imaging; brain imaging /visualization /scanning; choline; cingulate gyrus; clinical research; corpus callosums; creatine; developmental neurobiology; hippocampus; human subject; intelligence; limbic system; magnetic resonance imaging; middle childhood (6-11); neuroanatomy; neurochemistry; occipital lobe /cortex; prefrontal lobe /cortex; putamen; thalamus

Increasingly, clinical and non-human primate studies suggest that dysfunction in identified neural networks linking the limbic structures and the prefrontal cortex results in behavioral and emotional patterns that resemble autism. Neuroimaging techniques to date have not consistently identified brain abnormalities associated with autism. This likely due to heterogeneity of autistic populations, inadequate control populations and limitations of previous imaging techniques themselves. This project will use technological advances in structural and spectroscopic magnetic resonance imaging (sMRI and 1/H-MRSI and 1/H- MRSI) to investigate abnormalities in identified limbic-prefrontal neural networks and determine their association with autism. Seventy-two children and adolescents with autism aged 7;0 to 18;11 years and a group comparable in age, gender and IQ without autism will receive high resolution sMRI. From the MR images, total and separate brain tissue (white matter/gray matter, cerebrospinal fluid) volume measurements will be performed (a) on the different structures of the limbic regions, i.e. the amygdala and hippocampus and (b) on two regions of the prefrontal cortex, i.e., the orbitofrontal and dorsolateral white/gray matter volume differences in orbitofrontal cortex of all autistic people as compared to control subjects; that volumetric differences in the structures of the M-ORB/AMYG circuit will correlate more strongly with neuropsychological test indices measuring functions of the amygdala and the orbitofrontal cortex, and clinical and behavioral measures of autistic symptoms (e.g. severity of autism), than with IQ measures; and that the dorsolateral prefrontal-hippocampal (DL/HIPPO) circuit will be more severely affected in low-functioning children and adolescents with autism than in high-functioning children and adolescents with autism and controls. In addition, a subgroup of subjects including 20 young high- functioning children and adolescents persons with autism, age 11; 0 to 18; 11 years and 20 controls matched for age, gender, IQ, and handedness will receive 1/H-MRSI to assess the chemical composition for identified cerebral areas. In addition, all monkeys with infant and adult lesions in defined cerebral structures will be behaviorally tested (Project III) and imaged using the same technique to identify brain regions affected by the early versus late damage to the amygdala or orbitofrontal cortex. We hypothesize that abnormalities seen in higher-functioning children and adolescents with autism will be localized in the M-ORB/AMYG circuit, and those seen in the DL/HIPPO circuit will be associated with intellectual impairment; abnormalities of NAA reflecting alterations in neuronal integrity of the M-ORB-AMYG in autistic people will more strongly correlate with clinical and behavioral traits of autism as well as with scores on neuropsychological tasks measuring function of the M- ORB/AMYG circuit (Project I); in monkeys, we hypothesize that an early (infantile) lesion within the M-ORB/AMYG circuit (Project III) will have functional ramifications in other neural circuits (DL/HIPPO) and that the same lesion performed in adulthood will not have the same widespread impact.

越来越多的临床和非人类灵长类动物研究表明 连接边缘结构的确定神经网络的功能障碍 前额叶皮层导致行为和情感模式 这类似于自闭症。迄今为止的神经影像学技术还没有 一贯发现与自闭症相关的脑异常。这 可能是由于自闭症种群的异质性，控制不足 以前的成像技术本身的种群和局限性。 该项目将在结构和 光谱磁共振成像（SMRI和1/H-MRSI和1/H- MRSI）调查已鉴定的边缘前额外的异常 神经网络并确定其与自闭症的关联。七十二 自闭症年龄7; 0至18岁的儿童和青少年； 11岁 年龄，无自闭症的性别和智商会很高 分辨率SMRI。从MR图像中，总脑组织和分开的 （白质/灰质，脑脊液）的体积测量值 在边缘区域的不同结构上进行（a），即 杏仁核和海马以及（b）在前额叶的两个区域 皮质，即眶额和背外侧白色/灰质 所有自闭症患者的轨道额皮层的体积差异 与对照对象相比；在 M-ORB/AMYG电路的结构将与 神经心理测试指数测量杏仁核和 眶额皮质以及临床和行为度量 自闭症症状（例如自闭症的严重程度），而不是智商措施；和 背外侧前额叶海马（DL/HIPPO）电路将是 在低功能的儿童和青少年中受到更严重的影响 自闭症比具有自闭症和自闭症和青少年的高功能 控件。此外，包括20个年轻高级的受试者子组 自闭症患有自闭症的儿童和青少年，现年11岁； 0至 18;年龄，性别，智商和握手的11年和20个控件匹配 将收到1/h-MRSI以评估已鉴定的化学成分 脑区域。此外，所有患有婴儿和成人病变的猴子 在定义的脑结构中，将在行为上进行测试（项目III） 并使用相同的技术成像以识别受影响的大脑区域 通过对杏仁核或眶额皮质的早期损害与晚期损害。 我们假设在较高功能的儿童中看到异常 自闭症的青少年将位于M-ORB/AMYG电路中， 在DL/Hippo电路中看到的那些将与 智力障碍； NAA异常反映了变化 自闭症患者M-Orb-Amyg的神经元完整性将更多 与自闭症的临床和行为特征密切相关 就像在测量M-的神经心理任务的分数一样 ORB/AMYG电路（项目I）；在猴子中，我们假设这是早期的 M-ORB/AMYG电路（项目III）内的（婴儿）病变将具有 其他神经回路（DL/HIPPO）的功能分析， 在成年期进行的相同病变不会具有相同的广泛性 影响。