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）：所有皮质下排列主要为核排列。大脑皮层是大脑中最先进化出放射状和层状排列的细胞的部分。由此产生的模块化安排是基于细胞微柱：一个独立的生态系统连接传入，传出和神经元间的连接。我们对大脑皮层的基本处理单元微柱的初步研究表明，自闭症患者大脑中的模块化新皮层组织与对照组不同。更具体地说，一项对9名自闭症患者大脑中的3个新皮质部位和相同数量的正常对照的研究表明，分隔微柱的水平间距存在显着差异。它还揭示了它们内部结构的差异：微柱周围的神经元空间较少，平均细胞间距增加。类似的异常现在已经报道在伯格综合征，但似乎没有在唐氏综合征（一个对照组增加了精神发育迟滞）。 这项研究将研究24名自闭症患者和24名对照者之间的微柱形态测量学差异，年龄和性别相匹配，来自自闭症组织计划和Yakovlev-Haleem收藏（武装部队病理学研究所）。患者提供了一个新的队列，之前没有被研究者检查过。10个唐氏综合症大脑将提供第二个对照组。采样的皮质区域包括布罗德曼区域4、9、10、17、21、22、30、33和39，其代表从4个不同的脑叶获得的感觉、运动、关联和边缘皮质。这项研究将利用量化的计算机成像和体视学在尼氏和髓鞘染色的材料。测试的参数包括微柱的宽度、微柱内神经元空间的量、每个微柱内的平均细胞密度、单个板层深度、细胞大小和类型（锥体与非锥体）以及不同板层之间细胞类型的分布。这项研究将采用髓鞘间束测量作为一种方式来证实我们的minicolumnar宽度参数。我们将比较皮质多个区域内的结果以及偏侧化。最后，我们将我们的minicolunmar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。如果得到证实，我们研究的积极结果将使我们对自闭症有更好的了解。例如，许多所谓的自闭症动物模型缺乏人类神经解剖学信息来证明其实用性。如果能更好地理解自闭症的神经解剖学发展，候选基因的研究也可以得到完善。治疗方式，特别是神经药物，将被证明是更具体的，因为他们的目标是更好地理解。