Linking membrane voltage dynamics to fMRI measurement of functional connectivity in resting state and task related activities

将膜电压动力学与静息状态和任务相关活动中功能连接的功能磁共振成像测量联系起来

• 批准号: 10751310
• 负责人: Lisa M Meyer-Baese
• 金额: $ 4.77万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751310
• 关键词: Alzheimer' s Disease; Area; Basal Ganglia; Behavioral; Bilateral; Blood Vessels; Brain; Brain Diseases; Brain region; Cognitive; Complex; Data; Dependence; Detection; Diagnosis; Disease; Distant; Dorsal; Frequencies; Functional Magnetic Resonance Imaging; Future; Goals; Head; Health; Human; Image; Learning; Link; Measurable; Measurement; Measures; Membrane; Mental Depression; Mental disorders; Methods; Motor; Mus; Nature; Neurons; Outcome; Pathway Analysis; Pattern; Performance; Physiological; Population; Prefrontal Cortex; Process; Property; Proteins; Proxy; Publishing; Regulation; Reporting; Research; Rest; Schizophrenia; Sensory; Signal Transduction; Testing; Time; Training; Work; awake; blood oxygen level dependent; brain health; cell type; excitatory neuron; hemodynamics; insight; memory consolidation; nervous system disorder; network dysfunction; neural; neural network; novel; optical imaging; prognostic; response; sensor; tool; translational impact; voltage

PROJECT ABSTRACT Functional connectivity (FC) has been found to be altered in a wide range of otherwise indistinguishable disease states. The most common tool to non-invasively study the organization of brain-wide FC networks is functional magnetic resonance imaging (fMRI). fMRI relies on an indirect and indiscriminate measure of activity through the blood oxygen level-dependent (BOLD) contrast mechanism. By capturing fluctuations in the BOLD signal fMRI can detect distant synchronization between brain regions either at rest or during the performance of a specific task. These regions are inferred to be functionally connected and are thought to involve the synchrony of neuronal populations involved in a common function that are wired together through plasticity. Interpretation of FC networks derived from BOLD fMRI studies is currently limited by 1) the dependence of fMRI BOLD signals on hemodynamic changes as a proxy for neural activity and 2) a limited understanding of the mechanistic basis for FC in the context of behaviorally relevant longitudinal reorganizations. My long-term goal is to better understand the relationship between BOLD and neural activity in behaviorally relevant multi-regional circuits to advance brain network analysis. Once we know how both vascular and neural changes influence FC, the basis for network dysfunctions can be exploited with fMRI providing more robust fMRI-based disease detection. In this proposed project, I will use EMX1-Cre mice expressing a novel JEDI-1P voltage fluorescent protein in excitatory neurons across dorsal cortex. This voltage sensor has a large spectral band, allowing us to record both slow, subthreshold voltage activity, and fast gamma band activity. Wide-field optical imaging will be combined with fMRI to link neuronal changes in FC to hemodynamic changes measured with fMRI. In Aim 1 I will image these JEDI-1P at resting state to establish the correspondence between membrane voltage dynamics and fMRI for resting state functional connectivity networks. In Aim 2 I will train these mice to perform a sensorimotor task. I will image them during task training to assess changes in FC due to learning. I hypothesize that the correlation between fMRI BOLD and neural activity will be regionally specific for both resting state and task training, the latter will result in a measurable strengthening of FC between task-relevant areas. Completion of these aims will determine how functional networks observed with BOLD relate to neural activity and will provide insights into how FC reflects behaviorally relevant changes in the learning of a sensorimotor task. This results in a sharper understanding of the properties of neural network activity, its dependencies, and how to harness it in future fMRI studies.

项目摘要 功能连接（FC）被发现在多种其他无法区分的疾病中发生改变 州。非侵入性研究全脑 FC 网络组织的最常用工具是功能性的 磁共振成像（fMRI）。 fMRI 依赖于通过间接和不加区别的活动测量 血氧水平依赖性（BOLD）对比机制。通过捕捉 BOLD 信号的波动 功能磁共振成像可以检测休息时或执行任务期间大脑区域之间的远程同步。 具体任务。这些区域被推断在功能上是相连的，并且被认为涉及同步性 参与共同功能的神经元群通过可塑性连接在一起。解释 来自 BOLD fMRI 研究的 FC 网络目前受到 1) fMRI BOLD 信号依赖性的限制 血流动力学变化作为神经活动的代表；2）对其机制基础的了解有限 FC 在行为相关的纵向重组的背景下。我的长期目标是更好 了解行为相关多区域回路中 BOLD 和神经活动之间的关系 先进的脑网络分析。一旦我们知道血管和神经变化如何影响 FC，我们就可以得出以下结论： 可以通过 fMRI 来利用网络功能障碍，提供更强大的基于 fMRI 的疾病检测。 在这个拟议的项目中，我将使用表达新型 JEDI-1P 电压荧光蛋白的 EMX1-Cre 小鼠 背皮层的兴奋性神经元。该电压传感器具有较大的光谱带，使我们能够记录 缓慢的亚阈值电压活动和快速的伽玛带活动。宽视场光学成像将 与功能磁共振成像 (fMRI) 相结合，将 FC 中的神经元变化与功能磁共振成像 (fMRI) 测量的血流动力学变化联系起来。目标 1 I 将在静息状态下对这些 JEDI-1P 进行成像，以建立膜电压动态之间的对应关系 和用于静息状态功能连接网络的功能磁共振成像。在目标 2 中，我将训练这些小鼠执行 感觉运动任务。我会在任务训练期间对它们进行成像，以评估由于学习而导致的 FC 变化。我假设 fMRI BOLD 与神经活动之间的相关性对于静息状态和神经活动而言具有区域特异性 任务培训，后者将导致任务相关领域之间的 FC 得到可测量的加强。完成 这些目标中的一个将决定用 BOLD 观察到的功能网络如何与神经活动相关，并将提供 深入了解 FC 如何反映感觉运动任务学习中行为相关的变化。这导致 更深入地了解神经网络活动的属性、其依赖性以及如何利用它 未来的功能磁共振成像研究。