Disconnection as a model for cognitive dysfunction in multiple sclerosis

断开连接作为多发性硬化症认知功能障碍的模型

• 批准号: 8279855
• 负责人: Eric Klawiter
• 金额: $ 17.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8279855
• 关键词: Address; Affect; Anisotropy; Area; Atrophic; Attention; Award; Biological; Biological Neural Networks; Brain; Brain region; Clinical; Clinical Research; Clinical Trials; Cognition; Cognitive; Contralateral; Corpus Callosum; Coupled; Data; Demyelinations; Detection; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Digit structure; Disease; Disease Marker; Dorsal; Effectiveness; Employment; Episodic memory; Equilibrium; Etiology; Evaluation; Exhibits; Frequencies; Functional Imaging; Funding; Future; Hippocampus (Brain); Human; Image; Image Analysis; Imaging Device; Impaired cognition; Individual; K-Series Research Career Programs; Lesion; Magnetic Resonance Imaging; Measures; Mentors; Modality; Modeling; Monitor; Multiple Sclerosis; Neuraxis; Neurologic; Neuropsychological Tests; Outcome; Outcome Measure; Pathogenesis; Pathology; Patients; Phenotype; Preparation; Quality of life; Relative (related person); Research; Research Activity; Rest; Role; Signal Transduction; Techniques; Technology; Testing; Time; Tissues; Training; Training Activity; base; blood oxygen level dependent; cognitive neuroscience; disability; gray matter; imaging modality; improved; insight; interest; neuroimaging; novel therapeutic intervention; prevent; white matter; young adult

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. ) PUBLIC HEALTH RELEVANCE: This study aims to provide insight into the cause of cognitive dysfunction in multiple sclerosis, a leading non-traumatic cause of disability in young adults, by examining resting state functional connectivity MRI. New functional markers of the disease will be developed for future application to monitor the effectiveness of new treatments for multiple sclerosis. This study may aid in the development of future therapies specifically targeted to prevent or improve cognitive dysfunction in multiple sclerosis.

描述(由申请人提供)：应聘者正在寻求K23职业发展奖，以在多发性硬化症(MS)的神经成像领域进行临床研究。该奖项将提供受保护的研究时间和培训，为独立的R01基金做准备。这个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和临床问题的专家。霍华德·韦纳博士将担任第二导师，借助于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。认知功能障碍在多发性硬化症中很常见，并导致失业和生活质量下降。通过探索脑区的连通性，静息状态功能连通性(FcMRI)有可能提高对MS发病机制的理解，同时作为一种独特的认知检查手段。候选人将把大脑半球间的功能性连通性与解剖学连通性的测量方法(胼胝体弥散张量成像)和胼胝体萎缩联系起来，这在MS中是常见的发现。将这些测量关联起来将有助于评估MS认知功能障碍中的债务人的功能作用。我们还将探索皮质病理，如超高场(7T)所示，如何影响局部受限区域的连接，称为局部连接。3T的fcMRI和7T的皮质损伤测量都将与神经心理测试相关联，以帮助解决白质和灰质病理如何不同地导致认知功能障碍。除了有指导的研究活动，量身定制的教学课程和其他培训活动将为候选人提供成像分析和认知神经科学方面的正式教育。) 公共卫生相关性：这项研究旨在通过检查静息状态功能连接MRI，深入了解多发性硬化症认知功能障碍的原因，多发性硬化症是年轻人残疾的主要非创伤性原因。该疾病的新功能标记物将被开发用于未来的应用，以监测多发性硬化症新疗法的有效性。这项研究可能有助于开发未来专门针对预防或改善多发性硬化症认知功能障碍的疗法。