Gross morphological correlates to the minicolumnopathy of autism

总体形态学与自闭症的微小柱状病相关

• 批准号: 7838576
• 负责人: Manuel F Casanova
• 金额: $ 28.76万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7838576
• 关键词: Accounting; Adrenal Cortex Hormones; Affect; Age; Algorithms; Apical; Applications Grants; Area; Autistic Disorder; Autopsy; Award; Behavior; Body Image; Body Size; Brain; Case Series; Celloidin; Cells; Cerebral cortex; Clinical; Cluster Analysis; Code; Cognitive; Comparative Anatomy; Controlled Study; Corpus Callosum; Data; Development; Diagnosis; Diagnostic; Disease; Documentation; Electroencephalography; Elements; Evolution; Fiber; Grant; Gray unit of radiation dose; Homologous Gene; Image; Interneurons; Interview; Left; Link; Magnetic Resonance Imaging; Measurement; Measures; Microscopic; Modality; Morphologic artifacts; Morphology; Motor Cortex; Neocortex; Neurons; Neuropil; Pathology; Pathway interactions; Patients; Peripheral; Physiological; Primates; Process; Pyramidal Cells; Radial; Reporting; Request for Applications; Research; Research Personnel; Rodent; Sampling; Scheme; Screening procedure; Sensory; Series; Severities; Shapes; Specimen; Staining method; Stains; Structure; Surface; Symptoms; Synapses; Syndrome; Techniques; Testing; Time; Tissues; Trees; Variant; Width; Wit; area striata; base; brain size; comparative; endophenotype; falls; imaging modality; in vivo; indexing; innovation; morphometry; neuroimaging; neuronal cell body; programs; public health relevance; sex; white matter

DESCRIPTION (provided by applicant): The minicolumn is a basic anatomical and physiological element of the mammalian cerebral cortex, comprising a linear array of pyramidal cell bodies, their projections, and accompanying GABAergic interneurons. Postmortem studies of the organization of pyramidal cell arrays in autism have revealed that minicolumns in the brains of autistic patients are narrower. Since the minicolumn re-iterates itself millions of times throughout the brain, variations in the total number and width of minicolumns may result in macroscopic changes to the brain's surface area, folding (gyrification), and white matter pathways linking regional networks of minicolumns. In effect, data derived from comparative anatomy studies indicates that minicolumnar findings, if generalized, have specific gross correlates that can be detected by MRI. These changes include alterations in the gyral window, gray/white matter ratio, parcellation of the white matter, and size of the corpus callosum. This grant proposes studying a unique series of cases (n = 58) derived from the Autism Tissue Program (ATP). All of the cases included in this study had clinical documentation and a postmortem MRI. Autism was diagnosed according to DSM-IV-TR and ADI-R criteria. There are three specific aims to our study: 1) To quantify and compare the radial structure of dendritic bundles in the cerebral cortex of postmortem autistic patients and controls, 2) To determine the correlation between minicolumnar structure defined by fiber bundles and white matter distribution in the brains of postmortem autistic patients and controls, and 3) To perform a cluster analysis of autism diagnostic criteria and morphometric measurements. Specific aim 3 is an exploratory study that will attempt to provide construct validity to a current diagnostic scheme (ADI-R) by correlating clinical parameters to obtained neuropathological/neuroimaging data. All of the aims are in-keeping with the research objectives of the applied request for applications (RFA-MH-09-170). In order to achieve our specific aims the proposed study will correlate anthropometric indices (MRI) to specific minicolumnar parameters. Postmortem data will be derived from the analysis of apical dendritic bundles in nine cortical areas that display varying degrees of cytoarchitectural differentiation: paralimbic, high- order (hetermodal) association, modality-specific (unimodal) association, and idiotypic areas (primary sensory/motor cortices) (BA 4, 9, 10, 17, 21, 22, 33, 39, and 40). Other areas, i.e., corticoid and all cortical formations, were not included in our sampling scheme due to their lack of minicolumnar organization. The analysis of specific minicolumnar compartments will allow us to screen a series of anatomical elements incriminated in previous studies, i.e., minicolumnar narrowing most prominently in the peripheral neuropil space. Preliminary findings suggest: 1) high predictive ability between macro- and microscopic parameters, and 2) a high degree of diagnostic (autism) selectivity when combining the different anthropometric indices espoused in this grant proposal. PUBLIC HEALTH RELEVANCE: This project attempts to establish a correlation between autopsy and neuroimaging findings in autism. The intent is to develop markers of the condition that can be detected while the patient is alive. Another innovative aspect of the proposal is an attempt to validate current diagnostic screening techniques against autopsy findings.

描述（由申请人提供）：迷你柱是哺乳动物大脑皮层的基本解剖和生理元素，包括锥体细胞体的线性阵列，它们的投影，以及伴随的gaba能中间神经元。对自闭症患者大脑锥体细胞排列组织的死后研究表明，自闭症患者大脑中的小柱更窄。由于小柱在整个大脑中反复迭代数百万次，小柱的总数和宽度的变化可能导致大脑表面积的宏观变化，折叠（旋转），以及连接小柱区域网络的白质通路。实际上，来自比较解剖学研究的数据表明，小柱的发现，如果普遍化，具有特定的大体相关性，可以通过MRI检测到。这些变化包括脑回窗、灰质/白质比、白质包裹和胼胝体大小的改变。这项拨款建议研究一系列独特的病例（n = 58），这些病例来自自闭症组织计划（ATP）。本研究中所有病例均有临床记录和死后MRI检查。根据DSM-IV-TR和ADI-R标准诊断自闭症。我们的研究有三个具体目的：1)量化和比较死后自闭症患者和对照组大脑皮层树突束的径向结构；2)确定死后自闭症患者和对照组大脑中由纤维束定义的小柱状结构与白质分布的相关性；3)对自闭症诊断标准和形态计量学测量进行聚类分析。具体目标3是一项探索性研究，试图通过将临床参数与获得的神经病理/神经影像学数据相关联，为当前的诊断方案（ADI-R）提供结构效度。所有这些目标都符合申请申请（RFA-MH-09-170）的研究目标。为了实现我们的具体目标，提出的研究将人体测量指数（MRI）与特定的小柱参数相关联。死后数据将来自对9个皮层区域的顶端树突束的分析，这些区域显示出不同程度的细胞结构分化：旁边缘区、高阶（异模态）关联、模态特异性（单模态）关联和独特型区（初级感觉/运动皮质）（BA 4,9,10,17,21,22,33,39和40）。其他区域，即皮质和所有皮质地层，由于缺乏小柱状组织而未包括在我们的抽样方案中。具体的小柱室室的分析将使我们能够筛选一系列的解剖因素涉及到以前的研究，即，最突出的小柱狭窄在周围神经空间。初步研究结果表明：1)在宏观和微观参数之间具有较高的预测能力；2)在结合本资助提案中支持的不同人体测量指标时，具有高度的诊断（自闭症）选择性。