Project 3

项目3

• 批准号: 10470267
• 负责人: BRUCE R ROSEN
• 金额: $ 41.7万
• 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/10470267
• 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.

项目总结/摘要-项目3 我们建议利用我们最先进的功能性磁共振成像（fMRI）工具结合脑电图 (EEG)研究人类软脑膜神经血管回路这个电路是由软膜网络组成的 整合神经元活动与内在小动脉血管运动的小动脉，产生动态模式， 小动脉直径的相干振荡，有效地包裹皮质套。 今天，功能磁共振成像是最广泛的工具，用于测量整个人类的神经活动， 个脑袋所有的fMRI信号都是血管起源的，因此正确解释这些血流动力学信号是关键， 了解潜在的神经活动我们的团队已经证明了动脉中的自发振荡 大脑皮层中的血管直径或血管运动由局部神经活动引起， 通过沿着血管的主动信号传导， 内皮细胞这激发了U19的中心假设-局部神经元驱动和神经调节 具有超低频分量的输入与小动脉的固有振荡特性竞争。这 允许不同的皮层区域以不同的频率振荡， 血管动力学和时间相干区域的不同星座的形成。的耦合 动脉振荡将引起下游静脉血氧合的耦合，这是血液循环的基础。 氧合水平依赖（BOLD）对比度，最常用的fMRI信号。 在目标1中，我们将调整我们的非侵入性成像工具，以成像人体软脑膜的解剖结构和动力学 动脉血管网然后，我们将开发新的工具来测量软脑膜小动脉的直径变化， 直接追踪人类的血管运动，并将这些动力学与标准的功能磁共振成像测量相联系。我们的目标2是人类 项目1的对应物;我们将研究软脑膜神经血管对多种感觉驱动的血管整合 回路及其在大尺度血流动力学中的反映。我们的目标3是项目2的人类对应物;我们将 同时记录BOLD功能磁共振成像和脑电图在自发波动唤醒状态，并确定如何 大脑内部状态与我们的成像读数的空间模式有关。与项目2类似，我们将测试 这些血流动力学模式，单独或与EEG信号结合，是否可以用来预测认知功能， 性能最后，我们将与项目4一起设计一个现象学数学模型 它从血管整合器产生大规模的 连贯的血管/血液动力学波动模式。影响：项目3将提供强大的生理 为人类大规模fMRI信号的解释和更好地理解 将自发神经血管活动与认知表现联系起来的机制。总的来说，我们的计划将 在人类功能性磁共振成像的可观察性和潜在的内部大脑状态之间建立反向联系， 包括从非侵入性测量推断神经调节动力学。