STRUCTURAL AND SPECTROSCOPIC BRAIN MRI IN AUTISM

自闭症患者的结构和能谱脑 MRI

• 批准号: 6442980
• 负责人: MICHAEL E. BRANDT
• 金额: $ 16.41万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6442980
• 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 已确定的连接边缘结构的神经网络功能障碍 前额皮质导致行为和情绪模式 类似于自闭症。迄今为止，神经影像技术还没有 一致发现与自闭症相关的大脑异常。这 可能是由于自闭症人群的异质性、控制不足 人群和先前成像技术本身的局限性。 该项目将利用结构和技术方面的先进技术 波谱磁共振成像（sMRI 和 1/H-MRSI 和 1/H- MRSI）以调查已识别的边缘-前额叶的异常 神经网络并确定它们与自闭症的关联。七十二 7岁、0岁至18岁、11岁的自闭症儿童和青少年及一组 年龄、性别和智商相当但没有自闭症的人将获得高分 分辨率 MRI。从 MR 图像中，可以看到完整的脑组织和单独的脑组织 （白质/灰质、脑脊液）体积测量将 (a) 对边缘区域的不同结构进行，即 杏仁核和海马体以及（b）前额叶的两个区域 皮质，即眶额和背外侧白/灰质 所有自闭症患者眶额皮层的体积差异为 与对照受试者相比；的体积差异 M-ORB/AMYG 电路的结构将与 测量杏仁核功能的神经心理学测试指标 眶额皮质，以及临床和行为测量 自闭症症状（例如自闭症的严重程度），与智商测量相比；和 背外侧前额叶-海马 (DL/HIPPO) 回路将 功能低下的儿童和青少年受到的影响更为严重 自闭症的发生率高于患有自闭症的高功能儿童和青少年 控制。此外，还有一个受试者小组，包括 20 名年轻高中生 功能正常的儿童和青少年、患有自闭症的人，11 岁； 0 至 18； 11 岁和 20 名对照者的年龄、性别、智商和惯用手相匹配 将收到 1/H-MRSI 来评估已识别的化学成分 大脑区域。此外，所有患有婴儿和成年病变的猴子 将在确定的大脑结构中进行行为测试（项目 III） 并使用相同的技术进行成像以识别受影响的大脑区域 杏仁核或眶额皮质的早期与晚期损伤。 我们假设功能较高的儿童中出现的异常 患有自闭症的青少年将被定位在 M-ORB/AMYG 回路中， DL/HIPPO 电路中看到的那些将与 智力障碍； NAA 的异常反映了 自闭症患者中 M-ORB-AMYG 的神经元完整性将更加明显 与自闭症的临床和行为特征也密切相关 与测量 M 功能的神经心理学任务分数一样 ORB/AMYG电路（项目I）；在猴子中，我们假设早期 M-ORB/AMYG 回路（项目 III）内的（婴儿）病变将有 其他神经回路（DL/HIPPO）的功能分支 成年后发生的相同病变不会有同样广泛的影响 影响。