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) 工具与脑电图相结合 （脑电图）研究人类的软脑膜神经血管回路该回路由软脑膜网络组成。 将神经活动与内在小动脉血管运动相结合的小动脉，产生动态模式 小动脉直径的相干振荡有效地分割了皮质套。 如今，功能磁共振成像 (fMRI) 是用于无创测量整个人类神经活动的最广泛的工具 所有功能磁共振成像信号均起源于血管，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的自发振荡。 大脑皮层的血管直径或血管舒缩受到局部神经活动的影响，并且小动脉 通过沿着血管的主动信号传导，充当与其他连接的小动脉的耦合振荡器 这激发了该 U19 的中心假设——局部神经元驱动和神经调节。 具有超低频成分的输入与小动脉的固有振荡特性竞争。 允许不同的皮质区域以不同的频率振荡并导致空间分割 血管动力学和时间相干区域的不同星座的形成。 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 氧合水平相关 (BOLD) 对比度是最常用的 fMRI 信号。 在目标 1 中，我们将采用无创成像工具对人体软脑膜的解剖结构和动力学进行成像 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，并将这些动态与标准功能磁共振成像测量联系起来，我们的目标 2 是人类。 项目1的对应部分；我们将研究软脑膜神经血管对多种感觉驱动的血管整合 我们的目标 3 是项目 2 的人类对应物； 在唤醒状态自发波动期间同时记录 BOLD fMRI 和 EEG，并确定如何 与项目 2 类似，我们将测试内部大脑状态与我们的成像读数的空间模式相关。 这些血流动力学模式是否可以单独使用或与脑电图信号结合使用来预测认知能力 最后，我们将与项目 4 一起设计一个唯象数学模型。 从血管积分器的角度捕捉大脑状态的本质，产生大规模的 影响：项目 3 将提供强大的生理功能。 为解释人类大规模功能磁共振成像信号和更好地理解 总的来说，我们的计划将把自发神经血管活动与认知表现联系起来。 建立人类功能磁共振成像观察结果与潜在的内部大脑状态之间的反向联系 包括从无创测量中推断神经调节动力学。