Establishing relationships between functional connectivity and activity dynamics

项目摘要 局灶性脑损伤通常导致脑网络结构的破坏，并引起显著的认知障碍。 损伤和残疾。尽管对人类大脑连接进行了广泛的研究，但基本问题仍然存在。 主要是关于静态功能连接的模式如何与大脑动力学（活动的变化）相关 随着时间的推移），最终产生思想和行动。这是科学进步的重大障碍， 因为在连接性-动力学关联得到更好的表征之前，认知和系统神经- 科学将缺乏继续发展强大的大脑功能理论所必需的关键知识。这是... 这项研究的目的是为脑连接与脑功能之间的关系提供重要的新见解， 和动力学，并告知我们的理解如何区域和分布式大脑动力学是不重要的， 受到脑损伤后的冲击并重组这项研究将使用健康人的静息fMRI数据 个体和患者与局灶性脑病变，以测试假设，大脑动力学是由功能， 在多个空间尺度上的连通性。先前的研究表明，对高度连接的“枢纽”的损害 区域破坏了功能性大脑网络的模块结构。多个计算模拟， 他们预测，大脑连接在塑造大脑动力学方面起着关键作用，但经验证据表明， 这些预测从未在人类身上进行过经验性的测试。在过去工作的指导下， 作为有希望的初步数据，两个具体目标将：1）调查区域连接之间的关系， 2）确定中枢损伤对分布式脑动力学的影响。第一个目标 将探索大脑区域的全脑连接概况在多大程度上影响其活动波动- 随着时间的推移，而第二个目标将调查高度连接的枢纽地区是否在形状中发挥关键作用， 分布式大脑动力学。拟议的研究是创新的，在其使用的分析技术， 图论，信息论和动力系统，以提出有关人脑的基本问题，或者- 健康和疾病的组织。它的重要性在于它将提供对职能组织的深入了解 并有可能为开发新的诊断评估提供信息， 治疗局灶性脑损伤后的脑功能障碍和认知障碍。除了亲- 提出的研究，一个全面的培训计划将为申请人提供显着的额外技能， 在收集高质量MRI数据、神经系统患者研究和使用分析方法方面的经验 图论、信息论和动力系统的技术。丰富的科学训练环境 在世界一流的大学将得到正式的课程，技术培训，研究经验， 以及与多位专家教师进行一对一指导。这一培训将直接促进持续的- 申请人作为一名富有成效的独立研究人员和学术科学家的成长。

PROJECT SUMMARY Focal brain lesions often result in disruption of brain network architecture and cause significant cognitive im- pairment and disability. Despite extensive research into human brain connectivity, fundamental questions re- main about how patterns of static functional connectivity are related to the brain dynamics (changes in activity over time) which ultimately give rise to thought and action. This is a significant barrier to scientific progress, because until connectivity-dynamics associations have been better characterized, cognitive and systems neu- roscience will lack key knowledge necessary to continue developing robust theories of brain function. The ob- jective of the proposed research is to provide important new insight into the relationship between brain connec- tivity and dynamics, and to inform our understanding of how regional and distributed brain dynamics are im- pacted by—and reorganized after—focal brain damage. This research will use resting fMRI data from healthy individuals and patients with focal brain lesions to test the hypothesis that brain dynamics are shaped by func- tional connectivity at multiple spatial scales. Prior studies have shown that damage to highly connected “hub” regions disrupts the modular architecture of functional brain networks. Multiple computational simulations fur- ther predict that brain connectivity plays a critical role in shaping brain dynamics, but empirical evidence is lacking and these predictions have never been empirically tested in humans. Guided by this past work, as well as promising preliminary data, two specific aims will: 1) Investigate the relationship between regional connec- tivity and dynamics, and 2) Determine the impact of hub damage on distributed brain dynamics. The first aim will explore the extent to which a brain region's whole-brain connectivity profile shapes how its activity fluctu- ates over time, while the second aim will investigate if highly connected hub regions play a critical role in shap- ing distributed brain dynamics. The proposed research is innovative in its use of analytic techniques from graph theory, information theory, and dynamical systems to ask fundamental questions about human brain or- ganization in health and disease. It is significant because it will provide insight into the functional organization of the human brain and has the potential to inform the development of novel diagnostic assessments and treatments for brain dysfunction and cognitive impairment following focal brain injury. In addition to the pro- posed research, a comprehensive training plan will provide the applicant with significant additional skills and experience in the collection of high-quality MRI data, studies of neurological patients, and the use of analytic techniques from graph theory, information theory, and dynamical systems. A rich scientific training environment at a world class university will be complimented by formal coursework, technical trainings, research experience and 1-on-1 mentoring with multiple expert faculty members. This training will directly contribute to the contin- ued growth of the applicant as an productive independent researcher and academic scientist.