Disconnection as a model for cognitive dysfunction in multiple sclerosis

描述（由申请人提供）：候选人正在寻求K23职业发展奖，在多发性硬化症（MS）的神经影像学领域进行临床研究。该奖项将提供受保护的研究时间和培训，为独立的R01资金做准备。该项目的主要导师是布鲁斯·罗森博士，他是应用功能成像工具解决特定生物学和临床问题的专家。霍华德韦纳博士将担任二级导师，借给他在多发性硬化症方面的著名专业知识。多发性硬化症是导致年轻人残疾的主要非创伤性原因。认知功能障碍在MS中很常见，并导致失业和生活质量下降。通过探索大脑区域的连接，静息态功能连接（fcMRI）有可能提高对MS发病机制的理解，同时作为一种独特的手段检查认知。候选人将功能性半球间连接与解剖连接的测量相关联（胼胝体中的扩散张量成像）和胼胝体萎缩，这是MS中的常见发现。将这些测量结果相关联将有助于评估胼胝体在MS中认知功能障碍中的功能作用。我们还将探讨皮质病理学如何在超高场（7T）下显示，影响局部约束区域中的连接，称为局部连接。3T的fcMRI和7T的皮质病变测量将与神经心理学测试相关，以帮助解决白色和灰质病理学如何不同地导致认知功能障碍。除了指导性的研究活动，量身定制的教学课程和其他培训活动将提供成像分析和认知神经科学的正式教育给候选人。)

DESCRIPTION (provided by applicant): The candidate is pursuing a K23 career development award to conduct clinical research in the area of neuroimaging in multiple sclerosis (MS). This award will provide protected research time and training in preparation for independent R01 funding. The primary mentor for this project is Dr. Bruce Rosen, an expert in applying functional imaging tools to solve specific biological and clinical problems. Dr. Howard Weiner will serve as the secondary mentor, lending his renowned expertise in MS. Multiple sclerosis is the leading non- traumatic cause of disability in young adults. Cognitive dysfunction is common in MS and contributes to loss of employment and reduced quality of life. By exploring connectivity of brain regions, resting-state functional connectivity (fcMRI) has the potential to improve the understanding of MS pathogenesis while serving as a unique means of examining cognition. The candidate will correlate functional inter-hemispheric connectivity with measures of anatomical connectivity (diffusion tensor imaging in the corpus callosum) and corpus callosum atrophy, a common finding in MS. Correlating these measures will help evaluate the functional role of the corpus callosum in cognitive dysfunction in MS. We will also explore how cortical pathology, as demonstrated at ultra-high field (7T), affects connectivity in a locally constrained area, termed local connectivity. Both fcMRI at 3T and cortical lesion measures at 7T will be correlated with neuropsychological testing to help address how white and gray matter pathologies differentially contribute to cognitive dysfunction. In addition to mentored research activities, tailored didactic coursework and other training activities will provide formal educatio in imaging analysis and cognitive neuroscience to the candidate. )