Investigating the Neuronal and Vascular Contributions to the Spontaneous BOLD fMRI Signal Fluctuations Underlying Functional Connectivity

磁共振成像(MRI)是一项强大的技术，为研究大脑提供了前所未有的机会。特别是，功能磁共振成像(FMRI)主要基于血氧水平的变化(血氧水平依赖(BOLD))，使测量大脑活动的相关性成为可能，并自那以来在医学和法医学的广泛领域得到了应用。最近，人们发现BOLD fMRI信号的自发波动可以用来衡量大脑区域之间的同步性(或连通性)。这项被称为功能连接(FcMRI)的技术在研究健康和疾病中的大脑方面显示出巨大的潜力。然而，尽管fcMRI被广泛认为反映了神经元的过程，但BOLD信号波动背后的实际机制仍然不完全清楚，这留下了误解fcMRI测量的巨大可能性。BOLD功能磁共振信号受到神经和血管机制的强烈调制，这两种机制都很难解决。一系列非神经元噪声源对大胆信号波动的贡献使情况更加复杂。这项拟议研究的总体目标是促进对功能连接的神经成像标志物的理解。首先，这项工作将提供新的MRI采集方法，以显著降低非神经元噪声对BOLD信号的贡献。随后，将提出新的分析框架，将这一新方法与脑生理学的各种MRI测量相结合，以帮助解决神经元和血管对BOLD fMRI信号波动的贡献，从而实现fcMRI测量。这项研究将为研究支撑大脑功能的生物物理机制提供新的神经成像技术，并将解决将尖端MRI技术更有效地转化为神经科学研究的迫切需要。

Magnetic resonance imaging (MRI) is a powerful technology offering unprecedented opportunities for studying the brain. In particular, functional MRI (fMRI), largely based on changes in blood oxygenation (blood-oxygen level dependent (BOLD)), has enabled the measurement of correlates of brain activity, and has since found applications in a wide range of areas spanning medicine and forensics. Recently, it was found that spontaneous fluctuations in the BOLD fMRI signal could be used to measure the synchrony (or connectivity) between brain regions. This technique, termed functional connectivity (fcMRI), has shown tremendous potential for studying the brain in health and disease. However, although fcMRI is widely assumed to reflect neuronal processes, the actual mechanisms underlying the BOLD signal fluctuations remain incompletely understood, leaving great potential for misinterpretation of fcMRI measurements. The BOLD fMRI signal is strongly modulated by both neuronal and vascular mechanisms, which are challenging to resolve. This is further complicated by the contribution from a range of non-neuronal noise sources to the BOLD signal fluctuations. The overall goal of the proposed research is to advance the understanding of neuroimaging markers of functional connectivity. First, this work will provide new MRI acquisition methods to significantly reduce the contribution of non-neuronal noise to the BOLD signal. Subsequently, new analyses frameworks integrating this new methodology and various MRI measures of brain physiology will be proposed to help resolve the neuronal and vascular contributions to fluctuations in the BOLD fMRI signal, hence fcMRI measures. This research will furnish novel neuroimaging techniques for examining the biophysical mechanisms underpinning brain function, and will address the urgent need for more effective translation of cutting-edge MRI techniques to neuroscience research.