Method for Measuring Functional Subunits in Human Cortex

描述（由申请人提供）：自从Broca和Wernicke的第一次病变研究以来，科学家们一直试图将功能与特定的皮层区域联系起来，并生成人类皮层的功能图。基于组织学、形态学或功能（通过基于任务的fMRI和PET）的制图方法已被用于描绘大脑中的子区域。本文提出了一种通过分析静息状态连接数据来映射皮层亚基的新方法。总体目标是开发和验证一种方法，该方法使用静息状态fMRI连接数据来描绘整个大脑中每个皮层和皮层下区域的功能亚基，并基于这些功能亚基生成全脑概率图谱。然后，这些亚单位为网络分析提供了一个起点，最终导致人类连接组。目的是扩展我们的工作算法，以包括额外的空间约束，并使用3种验证方法在健康对照受试者的数据上验证算法。最终目的是在顽固性癫痫患者中试验这种方法，以验证这种方法允许识别可能与癫痫发作相关的特定异常节点或网络的假设。整个大脑的功能亚基图的直接实际用途将是提供一个框架，以简化传统的基于任务的神经成像结果的分析、解释和报告，旨在确定这些区域的特定功能。生成的图谱还将提供一个基础集，从中可以对比一系列神经系统疾病，以揭示可能受疾病影响的异常功能单位和/或网络。这项工作可能对这些方法的翻译临床应用，以及对一系列神经系统疾病（如阿尔茨海默病、帕金森病、多发性硬化症和癫痫）和精神疾病（如精神分裂症）对大脑功能组织的影响产生重大影响。最后，这项工作将提供一种评估这些功能亚基组织的个体差异的方法，可能导致在没有任务型功能磁共振成像的限制下研究疾病、遗传和环境影响的方法。

DESCRIPTION (provided by applicant): Since the first lesion studies of Broca and Wernicke scientists have been trying to relate function to specific cortical areas and to generate functional maps of the human cortex. Mapping approaches based on histology, morphology, or function (through task-based fMRI and PET), have been used to delineate sub-regions in the brain. This proposal presents a new approach for mapping cortical subunits through analysis of resting-state connectivity data. The over-arching goal is to develop and validate a method that uses resting-state fMRI connectivity data to delineate functional subunits within each cortical and subcortical region throughout the brain and to produce a whole-brain probabilistic atlas based on these functional subunits. These subunits then provide a starting point for network analysis leading ultimately to a human connectome. The aims are to extend our working algorithm to include additional spatial constraints, and to validate the algorithm on data from healthy control subjects using 3 validation approaches. The final aim is to pilot this approach in intractable epilepsy patients to test the hypothesis that this approach allows for the identification of specific abnormal nodes or networks that may be associated with seizure generation. The immediate practical use of a map of the functional subunits throughout the brain will be to provide a framework for simplifying the analysis, interpretation, and reporting, of conventional task-based neuroimaging results aimed at determining the specific functions of these areas. The atlas generated will also provide a basis set from which a range of neurological disorders may be contrasted to reveal abnormal functional units and/or networks that may be affected by disease. This work could have substantial impact in translation clinical application of these methods and in understanding the impact on the functional organization of the brain of a range of neurological disorders such as Alzheimer's, Parkinson's, MS, and epilepsy, and on psychiatric disorders such as schizophrenia. Finally, this work will provide a methodology for assessing individual variance in organization of these functional subunits potentially leading to methods that will allow the impact of disease, genetics, and environment, to be studied without the constraints of task-based fMRI. PUBLIC HEALTH RELEVANCE: This project is aimed at developing a method to produce an atlas of the functional subunits in the human brain. This work could have substantial impact in understanding the impact on the functional organization of the brain of a range of neurological disorders such as Alzheimer's, Parkinson's, MS, and epilepsy and on psychiatric disorders such as schizophrenia. It also represents the first step in the path towards a human connectome.