STRUCTURAL AND SPECTROSCOPIC BRAIN MRI IN AUTISM

越来越多的临床和非人类灵长类研究表明 已识别的连接边缘结构的神经网络功能障碍 前额叶皮质导致行为和情绪模式 类似自闭症的症状。神经成像技术到目前为止还没有 始终如一地发现与自闭症有关的大脑异常。这 可能是由于自闭症人群的异质性，控制不足 人群和以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) 磁共振成像)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 自闭症儿童和青少年7岁；0至18岁；11岁和一组 在年龄、性别和智商方面与自闭症相当的人将获得较高 分辨率sMRI。从磁共振图像看，整个脑组织和分离的脑组织 (白质/灰质，脑脊液)体积测量将 (A)对边缘区域的不同结构，即 杏仁核和海马体以及(B)前额叶的两个区域 皮质，即眶前叶和背外侧的白质/灰质 所有自闭症患者眶前叶皮质的体积差异 与对照受试者相比； M-ORB/AMYG电路的结构将与 测量杏仁核和大脑皮质功能的神经心理测试指标 眼眶前额叶皮质及临床和行为测量 自闭症症状(例如自闭症的严重程度)，而不是智商测量；以及 背外侧前额-海马区(DL/HIPPO)回路将是 在功能低下的儿童和青少年中受影响更严重 患有自闭症的高功能儿童和青少年的自闭症 控制。此外，包括20名年轻高中生在内的一组受试者 功能正常的儿童和青少年自闭症患者，年龄11岁；0至 年龄、性别、智商和惯用手相匹配的11岁和20名对照组 将接受1/H-MRSI以评估确定的化学成分 大脑区域。此外，所有患有幼猴和成年猴皮损的猴子 将对确定的大脑结构进行行为测试(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 由杏仁核或眶前叶皮质的早期损伤与晚期损伤所致。 我们假设，在功能较高的儿童中看到的异常 患有自闭症的青少年将定位于M-ORB/AMYG环路， 而在DL/河马赛道中看到的那些将与 智力损害；反映智力变化的NAA异常 自闭症患者M-ORB-AMYG的神经元完整性将更多 自闭症的临床和行为特征也与此密切相关 就像神经心理任务的分数一样，测量M- ORB/AMYG回路(项目I)；在猴子身上，我们假设早期的 M-ORB/AMYG环路内的(婴儿)损害(项目III)将 其他神经回路的功能分支(DL/河马)和 同样的病变在成年后不会有同样广泛的 冲击力。

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.