Time-varying spatiotemporal causal interactions in the functional brain networks

这份提案描述了一项为期五年的职业发展计划，为候选人徐楠博士 在一家大型学术研究机构担任独立调查员，具有建模专业知识 大脑因果系统的动力学，为神经疾病的基本病理生理学提供新的见解。 这项建议是基于徐南博士在数学建模和算法开发方面的专业知识而提出的 翻译神经疾病和治疗实践中的模型推理；同时培训她询问科学 与临床实践和神经生理学病理学有关的问题。PI将在Biomedical接受指导 佐治亚理工学院和埃默里大学的工程学，谢拉·凯尔霍尔茨博士(取决于血氧水平 (BOLD)动力学及其神经生理学起源)，文斯·卡尔霍恩(翻译图像分析和 生物标记物)和杰森·艾伦(神经疾病临床培训)。他们的互补专业知识将有所帮助 在她的分析专业知识和临床神经学和认知方面的问题之间架起一座桥梁 需要解决的神经科学问题。 在大脑因果系统中，证据表明定向信息传递可能不仅包括 力量，更是一种持续和一种能力。后两个指标意味着重要的神经科学方面 在过去没有得到很好的研究。它们可能在病理性功能障碍中发挥关键作用，如 脑震荡后80%的患者会出现前庭综合征。在派的论文工作中，一个创新的 开发了一种方法来预测前两个指标。在这项工作的基础上，新的理论和 在这项研究中，将开发计算方法来进一步评估 信息传递的强度和持续时间 (K99) 在此基础上，对信息能力进行了刻画 评估所有三个因果指标的时间变异性 (R00) 。对静止的大胆数据的因果估计 将根据同时记录的局域场势(LFP)数据的估计进行验证，并且任务- 调用的粗体数据( 适用于K99和R00 )。最后，调查结果( 在K99和R00中 )将被转化为临床 不同严重程度前庭综合征患者的研究。具体目标是：(1)模型和 计算脑功能区之间的时变时空功能因果相互作用；(2) 用多模式脑评价估计的时变因果指标的可靠性和敏感性 啮齿动物和人类的成像数据，以及(3)获取患者大脑中随时间变化的因果模式 不同严重程度的脑震荡后视觉运动敏感性，这是前庭综合征的一种类型 多见于脑震荡后的患者。 成功的项目完成将潜在地改变快速发展的动态建模领域 大脑因果系统，促进基础神经科学发现，实现神经学的全面识别 疾病，并启发新的动物实验来研究神经疾病。

This proposal describes a five-year career development program to prepare the candidate, Dr. Nan Xu, for a career as independent investigator at a major academic research institute, with the expertise of modeling dynamics of brain causal system to provide novel insights into the basic pathophysiology of neurologic disorders. This proposal develops upon Dr. Nan Xu’s expertise in mathematical modeling and algorithm development to translate model inferences in neurologic disorders and therapeutic practices; while training her to ask scientific questions relevant to clinical practice and neurophysiological pathology. The PI will be mentored at Biomedical Engineering at Georgia Tech and Emory University by Drs. Shella Keilholz (blood oxygenation level dependent (BOLD) dynamics and their neurophysiological origins), Vince Calhoun (translational image analysis and biomarkers), and Jason Allen (clinical training in neurologic disorders). Their complementary expertise will help PI to bridge the gap between her analytical expertise and problems in clinical neurology and cognitive neuroscience that need to be addressed. In the brain causal system, evidence has shown that the directed information transfer may comprise not only a strength, but also a duration and a capacity. The latter two metrics imply important neuroscientific aspects that have not been well studied in the past. They may play key roles in pathological dysfunctions such as the vestibular syndrome which occurs in 80% of patients following concussion. In PI’s thesis work, an innovative measure was developed to predict the first two metrics. Building upon this work, novel theoretical and computational approaches will be developed in this study to further evaluate the temporal variability in the strength and duration of information transfer (K99) , and then to characterize the information capacity as well as to evaluate the temporal variability of all three causal metrics (R00) . The causal estimates of resting BOLD data will be validated against the estimates of the concurrently recorded local field potential (LFP) data, and task- evoked BOLD data ( for both K99 and R00 ). Finally, findings ( in both K99 and R00 ) will be translated into clinical studies of patients with different severity of vestibular syndromes. The specific aims are to: (1) model and compute the time-varying spatiotemporal functional causal interactions among functional brain regions; (2) evaluate the reliability and sensitivity of the estimated time-varying causal metrics using multimodal brain imaging data of rodents and human, and (3) access the time-varying causal patterns in patient brains with different severity of post-concussive visual motion sensitivity, which is one type of vestibular syndromes that were commonly occurred in patients after concussion. Successful project completion would potentially transform the rapidly evolving field of dynamics modeling in brain causal system, facilitate basic neuroscience discovery, enable comprehensive identification of neurologic disorders, and inspiring new animal experiments for studying neurological diseases.