静息态功能磁共振的神经基础：基于大鼠中同时钙光纤记录和静息态功能磁共振的多模态研究

Resting-state fMRI has emerged as a prominent functional brain mapping method in the recent years, and it is capable of examining the brain functions from local to whole brain level at various physiological and pathological conditions. Therefore, it has been widely utilized to study almost all brain disorders, such as stroke, Schizophrenia and Alzheimer’s disease, and has advanced our understanding of those disorders. Despite its enormous popularity, resting-state fMRI’s neural basis is far from well understood at two different levels: first it is unclear why there is significant spontaneous fluctuations in resting-state blood-oxygenation level dependent (BOLD) signals; second it is unclear why those spontaneous fluctuations across different brain regions are correlated to form functional connectivity. To this end, we will develop simultaneous dual-color and multi-site calcium fiber photometry and resting-state fMRI in rats, which will be able to simultaneously record neural signals and resting-state BOLD signals. With this technique, we will examine the cell-type specific processes of resting-state neurovascular coupling, and furthermore the neural basis of resting-state functional connectivity. We hope this project will advance our understanding on the neural basis of resting-state fMRI, and provide basis for better interpretation of resting-state fMRI results, and ultimately improve its applicability in brain disorders and brain research.

静息态fMRI是近二十年来fMRI领域中发展的新方法，可以从局部到全脑范围检测脑功能网络及其在不同生理、病理状态下的改变。因此该方法被广泛应用于脑疾病的研究中，例如中风、精神分裂症、阿尔茨海默症等，提高了对脑疾病的机理认识。尽管得到了广泛的应用,静息态fMRI的神经基础还远未阐明,即不清楚为什么静息态下fMRI血氧水平依赖(BOLD)信号具有显著的自发波动，且不同脑区之间的自发波动具有相关性（即功能连接），这使得其结果难以解读，限制了其应用。为此，本项目将结合多学科方法，建立大鼠中双色和多脑区的同时钙光纤记录和静息态功能磁共振方法，可以同时记录脑活动和静息态BOLD信号。基于此，我们将研究静息态BOLD信号神经细胞类型特异性的神经血管耦合机理，以及静息态功能连接的神经机理。本项目将提高对静息态fMRI神经基础的认识，为静息态fMRI结果的解读提供依据，提高其在脑疾病、脑科学研究的可应用性。

功能磁共振成像（functional magnetic resonance imaging, fMRI）已被广泛应用于脑功能研究中。作为fMRI的生理基础，其信号的神经基础已被广泛研究，但是具体的机制极其复杂，仍未完全阐明。近年来静息态fMRI被广泛应用，但是和传统任务态fMRI相比，静息态下的fMRI信号神经基础更不明确。为了更好的研究fMRI神经血管耦合的过程，我们有必要同时记录神经和fMRI信号。为此，我们开发了一套新型的基于相机的、可扩展的同时钙光纤记录和fMRI同时记录的装置。利用该装置，我们记录了视觉刺激和静息态下的大鼠上丘和外侧膝状体的钙信号和fMRI信号。我们发现，在视觉刺激条件下，钙信号和fMRI信号具有很强的、空间特异性的耦合关系。而在静息态下，两者的耦合关系较弱，同时空间特异性较差，呈现较弥散的空间特征。同时，静息态下耦合关系的空间特异性也和fMRI数据前处理流程（如白质脑脊液信号回归、全局信号回归）相关。综上，我们的结果说明了静息态下和任务态下钙信号和fMRI信号不同的耦合关系，拓展了对fMRI信号的神经基础的认识。