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）：缩影是哺乳动物大脑皮层的基本解剖学和生理元素，其中包括一组线性的金字塔细胞体，其投影以及伴随的Gabaergic Interneurons。对自闭症的锥体细胞阵列组织的死后研究表明，自闭症患者大脑中的微型班级较狭窄。由于微型列在整个大脑中重新征集了数百万次，因此微小颜色的总数和宽度的变化可能会导致大脑表面积，折叠（Gyrification）以及关联微小夜间区域网络的白质途径的宏观变化。实际上，比较解剖学研究得出的数据表明，如果概括化，微牙的发现具有特定的总相关性，可以通过MRI检测到。这些变化包括在陀螺窗口的变化，灰色/白质比，白质的分析以及call体的大小。 该赠款提出了研究从自闭症组织程序（ATP）得出的一系列独特病例（n = 58）。这项研究中包括的所有病例均具有临床文档和后MRI。根据DSM-IV-TR和ADI-R标准诊断自闭症。 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测量。特定目标3是一项探索性研究，它将通过将临床参数与获得神经病理学/神经影像学数据相关联，以尝试为当前的诊断方案（ADI-R）提供构造有效性。所有目的都是遵守应用申请请求的研究目标（RFA-MH-09-170）。 为了实现我们的特定目标，拟议的研究将将人体测量指数（MRI）与特定的微型级参数相关联。验尸数据将从对九个皮质区域的顶端树突捆的分析得出，这些皮质区域显示不同程度的细胞结构分化：旁皮，高阶（Hetermodal）关联，态性特异性（单峰）（单峰）关联和异性型区域（初级感官/运动cortices）（初级/运动cortices）（BA 40）。其他领域，即皮质类似和所有皮质形成，由于缺乏微型典型组织组织，我们的抽样计划中未包括其他领域。对特定微型级室的分析将使我们能够在先前的研究中筛选出一系列的解剖因素，即在周围神经皮质空间中最突出的微型级别。初步发现表明：1）宏观和微观参数之间的高预测能力，以及2）在合并本赠款建议中所依赖的不同人体测量指数时，具有高度的诊断（自闭症）选择性。 公共卫生相关性：该项目试图在自闭症中建立尸检与神经影像学发现之间的相关性。目的是开发患者还活着时可以检测到的疾病的标记。该提案的另一个创新方面是试图验证针对尸检结果的当前诊断筛查技术。