Project 3

项目3

• 批准号: 10294714
• 负责人: BRUCE R ROSEN
• 金额: $ 27.93万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-16 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10294714
• 关键词: Affect; Anatomy; Angiography; Arousal; Arteries; Blood; Blood Vessels; Blood Volume; Brain; Caliber; Cerebral cortex; Contrast Media; Coupled; Coupling; Electroencephalography; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Human; Image; Imaging Device; Iron; Link; Measurement; Measures; Methods; Morphology; Mus; Neurons; Pattern; Photic Stimulation; Physiological; Predisposition; Property; Resolution; Sensory; Signal Transduction; Stimulus; Testing; Time; Vascular Endothelium; Veins; Venous; Work; area striata; arteriole; base; behavioral response; blood oxygen level dependent; cognitive performance; experimental study; ferumoxytol; hemodynamics; imaging modality; mathematical model; multimodality; neuroregulation; neurovascular; non-invasive imaging; novel; programs; relating to nervous system; response; retinotopic; spatiotemporal; theories; tool; vasomotion; venule; visual stimulus

PROJECT SUMMARY/ABSTRACT – PROJECT 3 We propose to leverage our state-of-the-art functional MRI (fMRI) tools combined with electroencephalography (EEG) to investigate the pial neurovascular circuit in humans. This circuit is composed of a network of pial arterioles that integrate neuronal activity with the intrinsic arteriolar vasomotion, producing dynamic patterns of coherent oscillations in arteriolar diameter that effectively parcellate the cortical mantle. Today fMRI is the most widespread tool for measuring neural activity noninvasively across the entire human brain. All fMRI signals are vascular in origin, thus proper interpretation of these hemodynamic signals is key to understanding the underlying neural activity. Our team has demonstrated that spontaneous oscillations in arterial vascular diameter, or vasomotion, in the cerebral cortex is entrained by local neural activity, and that arterioles behave as coupled oscillators with other connected arterioles via active signaling along the vascular endothelium. This motivates the central hypothesis of this U19—that local neuronal drive and neuromodulatory inputs with ultralow-frequency components compete with the intrinsic oscillatory properties of arterioles. This allows different cortical regions to oscillate at different frequencies and results in spatial parcellation of vasodynamics and the formation of different constellations of temporally coherent regions. The coupling of arterial oscillations will induce coupling of the downstream venous blood oxygenation that is the basis of Blood- Oxygenation Level Dependent (BOLD) contrast, the most commonly used fMRI signal. In Aim 1, we will adapt our noninvasive imaging tools to image the anatomy and dynamics of the human pial arterial vascular network. We will then develop novel tools to measure diameter changes of pial arterioles to directly track vasomotion in humans, and link these dynamics to standard fMRI measures. Our Aim 2 is a human counterpart of Project 1; we will study vascular integration of multiple sensory drives by the pial neurovascular circuit and its reflection in large-scale hemodynamics. Our Aim 3 is the human counterpart of Project 2; we will record BOLD fMRI and EEG simultaneously during spontaneous fluctuations in arousal state, and identify how internal brain states are linked to spatial patterns of our imaging readouts. Similar to Project 2, we will test whether these hemodynamic patterns, alone or in combination with EEG signals, can be used to predict cognitive performance. Finally, we will work throughout with Project 4 to devise a phenomenological mathematical model that captures the essence of a brain state from the standpoint of the vascular integrator producing large-scale patterns of coherent vascular/hemodynamic fluctuations. Impact: Project 3 will offer a strong physiological foundation for the interpretation of large-scale fMRI signals in humans and better understanding of the mechanisms linking spontaneous neurovascular activity to cognitive performance. Overall, our program will establish an inverse link between human fMRI observables and the underlying internal brain state, potentially including inference of neuromodulatory dynamics from noninvasive measurements.

项目摘要/摘要 - 项目3 我们建议利用我们最先进的功能性MRI（fMRI）工具与脑电图结合 （脑电图）研究人类的脊髓神经血管回路。该电路由pial网络组成 将神经元活性与内在动脉血管瘤相结合的小动脉，产生动态模式 有效地将皮质地幔的小动脉直径的相干振荡。 如今，fMRI已成为整个人类无创神经活动的最广泛的工具 脑。所有fMRI信号的起源都是血管的，因此对这些血液动力学信号的正确解释是 了解潜在的神经活动。我们的团队证明了动脉的赞助振荡 大脑皮层中的血管直径或血管症。 通过沿血管的主动信号传导与其他连接的动脉相连的振荡器的行为表现 内皮。这激发了该U19的中心假设 - 局部神经元驱动和神经调节性 具有超频成分的输入与小动脉的内在振荡特性竞争。这 允许不同的皮质区域以不同的频率振荡，并导致空间分析 血管动力学和暂时相干区域不同星座的形成。耦合 动脉振荡将诱导下游静脉血氧的耦合，这是血液的基础 氧合水平取决于（粗体）对比度，是最常用的fMRI信号。 在AIM 1中，我们将适应非侵入性成像工具来形象人类的解剖学和动力学 动脉血管网络。然后，我们将开发新的工具，以测量伴侣小动物的直径变化 直接跟踪人类的血管舒张症，并将这些动力学与标准fMRI测量联系起来。我们的目标2是人类 项目1的对手；我们将研究多种感觉驱动器的血管整合。 电路及其在大规模血流动力学中的反射。我们的目标3是项目2的人类对应物；我们将 在唤醒状态下同时记录大胆的fMRI和EEG，并确定如何确定如何 内部大脑状态与我们的成像读数的空间模式有关。与项目2相似，我们将测试 这些血液动力学模式是否单独或与EEG信号结合使用，可以用于预测认知 表现。最后，我们将在整个项目4上工作，以设计一个现象学数学模型 从产生大规模的血管积分器的角度来捕获大脑状态的本质 相干血管/血流动力学波动的模式。影响：项目3将提供强大的生理 在人类中解释大型fMRI信号的基础，并更好地理解 将赞助神经血管活性与认知表现联系起来的机制。总体而言，我们的计划将 在人fMRI可观察到的内部大脑状态之间建立反向联系 包括从非侵入性测量中推断神经调节动力学。