Time-varying spatiotemporal causal interactions in the functional brain networks

功能性大脑网络中时变的时空因果相互作用

• 批准号: 10590411
• 负责人: Nan Xu
• 金额: $ 9.29万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590411
• 关键词: Address; Alzheimer' s Disease; Animal Experiments; Animal Model; Biological Markers; Biomedical Engineering; Blood Vessels; Brain; Brain Concussion; Brain Diseases; Brain imaging; Brain region; Clinical; Clinical Research; Cognitive; Communication; Commuting; Data; Development; Doctor of Philosophy; Functional Magnetic Resonance Imaging; Functional disorder; Human; Image Analysis; Impairment; Length; Measures; Mentors; Methodology; Methods; Modeling; Multimodal Imaging; Neurology; Neurons; Neurosciences; Pathologic; Pathology; Pathway interactions; Patients; Pattern; Performance; Phase; Play; Post-Concussion Syndrome; Postdoctoral Fellow; Program Development; Rehabilitation therapy; Research Institute; Research Personnel; Rest; Rodent; Role; Severities; Signal Transduction; Slide; Symptoms; Syndrome; System; Techniques; Testing; Therapeutic; Time; Training; Translating; Uncertainty; Universities; Variant; Visual Motion; Work; algorithm development; blood oxygen level dependent; career; career development; clinical phenotype; clinical practice; clinical training; cognitive neuroscience; experimental study; hemodynamics; image translation; imaging biomarker; innovation; insight; machine learning model; mathematical model; method development; motion sensitivity; multimodality; multisensory; nervous system disorder; neurophysiology; novel; patient response; response; spatiotemporal; visual-vestibular

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.

该建议描述了一项为期五年的职业发展计划，以准备候选人Nan Xu博士 在一家主要的学术研究所担任独立研究员的职业，具有建模的专业知识 脑因果系统的动力学，以提供新的见解神经系统疾病的基本病理生理学。 这项提出的发展是基于Nan Xu博士在数学建模和算法开发方面的专业知识 翻译神经系统疾病和治疗实践中的模型推断；在训练她问科学的同时 与临床实践和神经生理病理学有关的问题。 PI将在生物医学上考虑 Drs的佐治亚理工大学和埃默里大学的工程。 Shella Keilholz（血液氧合水平依赖） （粗体）动力学及其神经生理学的起源），文斯·卡尔洪（Vince Calhoun）（翻译图像分析和 生物标志物）和杰森·艾伦（Jason Allen）（神经系统疾病的临床培训）。他们的完整专业知识将有所帮助 PI弥合其分析专业知识与临床神经学和认知问题之间的差距 需要解决的神经科学。 在大脑因果系统中，有证据表明，定向的信息传输不仅可能构成 力量，但持续时间和能力。后两个指标暗示着重要的神经科学方面 过去一直没有很好的研究。他们可能在病理功能障碍中起关键作用，例如 咨询后80％的患者发生前庭综合征。在Pi的论文工作中，创新 制定了测量以预测前两个指标。在这项工作的基础上，新颖的理论和 本研究将开发计算方法，以进一步评估 信息传输的强度和持续时间 （K99） ，然后表征信息能力以及 评估所有三个因果指标的临时变异性 （R00） 。静止大胆数据的因果估计值 将根据同时记录的本地现场电位（LFP）数据以及任务 - 唤起大胆数据（ 对于K99和R00 ）。最后，发现（ 在K99和R00中 ）将翻译成临床 对前庭综合症严重程度不同的患者的研究。具体目的是：（1）模型和 计算功能性大脑区域之间的时变时空功能因果关系； （2） 使用多模式大脑评估估计的时变因子指标的可靠性和灵敏度 啮齿动物和人类的成像数据，以及（3）访问患者大脑中随时间变化的因果模式 脑震荡后视觉运动灵敏度的不同严重程度，这是一种前庭综合征 咨询后通常发生在患者中。 成功的项目完成可能会改变动态建模的快速发展的领域 脑因果系统，促进基本神经科学发现，使神经系统综合识别 疾病，并激发了研究神经系统疾病的新动物实验。