STRUCTURAL AND SPECTROSCOPIC BRAIN MRI IN AUTISM

越来越多的临床和非人类灵长类动物研究表明， 连接边缘结构的已识别神经网络功能障碍 而前额叶皮层会导致行为和情绪模式 类似自闭症的症状迄今为止，神经成像技术还没有 一致认为自闭症与大脑异常有关。这 可能是由于自闭症人群的异质性， 人口和以前的成像技术本身的局限性。 该项目将利用技术进步， 光谱磁共振成像（sMRI和1/H-MRSI和1/H-MRI） MRSI），以调查确定的边缘-前额叶 神经网络，并确定其与自闭症的关联。七十二 7岁、0至18岁、11岁和一组自闭症儿童和青少年 年龄、性别和智商相当，没有自闭症的人将获得高 分辨率sMRI。从磁共振图像来看，整个脑组织和单独的脑组织 （白色物质/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，以及（B）前额叶的两个区域 皮质，即，眶额和背外侧白色/灰质 所有自闭症患者的眶额皮质体积差异， 与对照组相比， 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数， 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），而不是智商测量;以及 背外侧前额叶-海马（DL/HIPPO）回路将 在低功能儿童和青少年中受影响更严重， 高功能自闭症儿童和青少年， 对照此外，一个包括20名年轻高- 功能正常的儿童和青少年自闭症患者，11岁; 0至 18岁; 11岁和20名年龄、性别、智商和利手相匹配的对照组 将接受1/H-MRSI，以评估确定的化学成分 大脑区域此外，所有患有婴儿和成年病变的猴子 将进行行为测试（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， 杏仁核或眶额皮层的早期和晚期损伤。 我们假设在高功能儿童中发现的异常 患有自闭症的青少年将局限于M-ORB/AMYG回路， 而在DL/HIPPO电路中看到的那些将与 智力障碍; NAA异常反映了 自闭症患者M-ORB-AMYG的神经元完整性将更 与孤独症的临床和行为特征密切相关 与神经心理学任务的得分一样， ORB/AMYG回路（项目I）;在猴子中，我们假设， M-ORB/AMYG回路内的（婴儿）病变（项目III）将具有 其他神经回路（DL/HIPPO）的功能分支， 在成年期进行的同样的损伤不会有同样广泛的 冲击

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.