Integration and Validation of Lesion Methods for Cognitive Neuroscience

描述(申请人提供)：损毁方法，它确定了脑损伤位置和获得性认知和行为损害之间的一致关系，继续是神经科学中识别更高功能的神经基础的不可或缺的方法。该项目的总体目标是将损伤方法建立在严格的、定量的基础上，并确定和扩展其限制，特别是关于定位的特异性和可解释性。我们将介绍将扩散张量成像中的连通性信息正式集成到基于体素的组级病变缺失分析中的方法。我们将调查现有的和新的方法的有效性、可靠性和解剖准确性，特别关注受试者群体的影响，病变覆盖的不均匀，以及灰质和白质损伤的不同作用。我们将通过两种方式验证基于体素的病变研究统计方法：1)基于大量真实大脑病变的模拟，捕捉自然病变样本的复杂结构的影响；2)在具有良好特征的视网膜组织视觉系统中的病变数据库中，将有多光谱MRI数据和广泛的功能评估(视网膜原位fMRI、多焦点视觉诱发电位、定量视野和代谢PET数据)。另一个首要目标是确定损伤方法的最佳实践，包括确定最佳(有效、敏感、有效)的分析形式，并为评估方法中的未来改进生成资源。最后，我们将把在这个项目中生成的方法、软件、验证数据集和性能基准传播给脑图社区。这里提出的工作将使损伤方法能够以前所未有的信心用于识别正常认知和行为所需的神经系统的基本组成部分。公共卫生相关性研究局灶性脑损伤的行为和认知后果提供了关于认知能力的大脑基础的信息，这些信息是无法从其他来源获得的。拟议的工作将有助于建立损害方法的最佳实践，使其更容易研究和理解中风和其他神经疾病造成的损害。

DESCRIPTION (provided by applicant): The lesion method, which identifies consistent relationships between sites of brain damage and acquired impairments of cognition and behavior, continues to be an indispensable approach in neuroscience for identifying the neural basis of higher function. The overall goal of this project is to put the lesion method on a rigorous, quantitative footing, and to determine and extend its limits, especially with respect to the specificity and interpretability of localization. We will introduce methods for formally integrating connectivity information, from diffusion tensor imaging, into group-level voxel-based lesion-deficit analyses. We will investigate the validity, reliability, and anatomic accuracy of existing and new methods, with particular attention to the impact of the subject group, non-uniform lesion coverage, and the different roles of gray and white matter damage. We will validate voxel-based statistical methods for lesion studies in two ways: 1) with simulations based on a large set of real brain lesions, that capture the effects of the complex structure of the natural lesion sample; and 2) in a well characterized database of lesions in the retinotopically organized visual system, for which there will be multispectral MRI data and extensive functional assessment (retinotopic fMRI, multifocal visual evoked potentials, quantitative visual fields, and metabolic PET data). Another overarching goal is to determine best practices for the lesion method, including identification of the optimal (efficient, sensitive, valid) forms of analysis and generation of resources for evaluating future improvements in the methods. Finally, we will disseminate methods, software, validation data sets, and performance benchmarks generated in this Project to the brain mapping community. The work proposed here will enable the lesion method to be used with unprecedented confidence to identify the essential components of neural systems for normal cognition and behavior. PUBLIC HEALTH RELEVANCE Studying the behavioral and cognitive consequences of focal brain damage provides information about the brain basis of cognitive abilities that can be gained from no other source. The proposed work will help establish best practices for the lesion method, making it easier to study and understand the impairments that result from stroke and other neurologic diseases.