Modular Abnormalities of Brain Organization in Autism

自闭症患者大脑组织的模块异常

• 批准号: 6827743
• 负责人: Manuel F Casanova
• 金额: $ 22.07万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6827743
• 关键词: autism; basal lamina; brain disorders; brain imaging /visualization /scanning; brain morphology; cell morphology; cell population study; cell type; cerebral dominance; clinical research; digital imaging; human tissue; mental disorder diagnosis; morphometry; neuropathology; parietal lobe /cortex; postmortem; temporal lobe /cortex; visual cortex

DESCRIPTION (provided by applicant): All subcortical arrangements are primarily nuclear in type. The cortex was the first part of the brain to evolve a radial and laminar arrangement of cells. The resultant modular arrangement is based on the cell minicolumn: a self-contained ecosystem of connectivity linking afferent, efferent and interneuronal connections. Our preliminary study of the fundamental processing unit of the cortex, the minicolumn, indicates that the modular neocortical organization in the brains of autistic individuals differs from that of controls. More specifically, a study of 3 neocortical sites in 9 autistic brains and an equal number of normal controls has shown significant differences in the horizontal spacing that separates minicolumns. It also revealed differences in their internal structure: less neuropil space in the periphery of the minicolumn and increased mean cell spacing. Similar abnormalities have now been reported in Asperger's syndrome but appear absent in Down syndrome (a control group added for mental retardation). This study will examine differences in minicolumnar morphometry between 24 autistic brains and 24 controls, matched for age and sex, from both the Autism Tissue Program and the Yakovlev-Haleem Collection (Armed Forces Institute of Pathology). The patients provide a new cohort not previously examined by the investigator. Ten Down syndrome brains will provide a second control group. Sampled cortical regions include Brodmann's areas 4, 9, 10, 17, 21, 22, 30, 33, and 39, which represent sensory, motor, association and limbic cortex obtained from 4 different brain lobes. The study will utilize quantified computer imaging and stereology in both Nissl and myelin-stained material. The parameters tested include the width of minicolumns, the amount of neuropil space within them, the mean cell density within each minicolumn, individual lamina depth, cell size and type (pyramidal versus non pyramidal), and the distribution of cell types among different lamina. The study will employ inter-myelinated bundle measurements as a way of corroborating our minicolumnar width parameters. We will compare the results within multiple regions of the cortex as well as for lateralization. Finally, we will correlate our minicolunmar parameters with different dimensions on the ADI. This study aims at better understanding the neuroanatomical basis of autism. If validated, positive results from our studies will yield a great understanding of autism. For example, many alleged animal models of autism lack the human neuroanatomic information to justify their utility. Candidate gene studies could also be refined if neuroanatomic development in autism was better understood. Treatment modalities, especially neuropharmaceutical agents, will prove more specific as their targets are better understood.

描述（由申请人提供）：所有皮层排列主要均在类型上核。皮层是大脑的第一部分，以进化细胞的径向和层状排列。最终的模块化排列基于细胞缩影：连接性，传出和神经间连接的连接性生态系统。我们对皮层基本处理单元（微型列）的初步研究表明，自闭症个体的大脑中的模块化新皮层组织与对照组的模块化不同。更具体地说，对9个自闭症大脑中的3个新皮层部位和相等数量的正常对照组的研究显示，在分离微小级别的水平间距上有显着差异。它还揭示了其内部结构的差异：微型列的周围中的神经纤维空间较少，平均细胞间距增加。现在已经报道了阿斯伯格综合症的类似异常，但在唐氏综合症中似乎没有（添加了智力低下的对照组）。 这项研究将检查24个自闭症大脑和24个对照之间的微型牙词形态计量学的差异，与年龄和性别相匹配，来自自闭症组织计划和Yakovlev-Haleem Collection（武装部队病理研究所）。患者提供了一个新的队列，以前未经研究者检查。十个唐氏综合症的大脑将提供第二个对照组。采样的皮质区域包括布罗德曼的4、9、10、17、21、22、30、33和39，这些区域代表从4个不同的脑叶获得的感觉，运动，关联和边缘皮层。该研究将利用NISSL和髓磷脂染色材料中的量化计算机成像和立体学。测试的参数包括微型级的宽度，其中的神经胶体空间的量，每个微型层中的平均细胞密度，单个层层深度，细胞大小和类型（金字塔和非金字塔）以及不同层中细胞类型的分布。这项研究将采用叶叶间捆绑测量值，以证实我们的微型级宽度参数。我们将比较皮质多个区域内的结果以及侧向化。最后，我们将将我们的微型符号参数与ADI上的不同尺寸相关联。这项研究旨在更好地了解自闭症的神经解剖学基础。如果得到验证，我们的研究的积极结果将对自闭症产生充分的了解。例如，许多所谓的自闭症动物模型缺乏人类的神经解剖学信息来证明其效用是合理的。如果更好地了解自闭症中的神经解剖学发展，也可以完善候选基因研究。治疗方式，尤其是神经药物的剂，由于对目标的理解得更好，因此将更加具体。