基于神经电活动光学成像的静息态脑功能连接研究

Spontaneous, low-frequency hemodynamic fluctuations in the brain could reflect the resting-state fucntional connectivity (RSFC). In recent years, a great deal of attention has been paid to study the brain functional networks using RSFC to provide new ways in early disgnosis and efficacy assessment of brain diseases. RSFC is widely evaluated by functional magnetic resonance imaging; however, the neural mechanisms underlying the spontaneous hemodynamic signals are not clear. The effects of consciousness of brain on the RSFC are controversial. Moreover, the neurovascular uncoupling may occur under some pathological conditions, and whether the RSFC evaluated by spontaneous hemodynamic fluctuations is a reliable indicator of neural functional connectivity has never been tested. Therefore, it is necessary to address these issues to provide the theoretical basis for accessing the brain functions by RSFC. Optical imaging has the advantage of acquiring rich parameters related to the brain functions by multiple imaging modalities. It can measure the hemodynamic signals including cerebral blood flow and blood oxygenation in real-time by optical intrinsic signals, and can also measure the neural electrical activities at high spatialtemporal resolution by exogenous dye-labeld fluorescence imaging. In this program, by measuring the neural electircal activities and the hemodynamic signals in experimental animals using optical imaging methods, we will try to explore the neural mechanisms underlying the RSFC based on spontaneous hemodynamic signals. We will also investigate the effects of neurovascular uncoupling on the RSFC in the disease models.

利用静息态脑功能连接（RSFC）技术研究脑功能拓扑结构，进而为脑疾病早期诊断与疗效评估提供新途径成为近年来神经科学领域研究的重要热点，特别是在功能磁共振成像领域引起了非常广泛的关注。但是，基于自发血液动力学信号RSFC的内在神经机制是什么？大脑意识状态对RSFC的影响如何？神经-血管耦合状态与调节机制对RSFC有何影响？特别是很多脑疾病可能会引起神经-血管耦合状态的改变，在此条件下，基于血液动力学信号的RSFC是否能准确反映神经功能连接状态？上述基础性的问题目尚未解决，亟待深入研究，阐明RSFC方法的生理基础及适用条件，为利用该方法进行脑疾病早期诊断与疗效评估提供理论基础。因此，本项目拟联合采用神经电活动光学成像和血液动力学光学成像技术在实验动物上开展静息态脑功能连接研究，探讨RSFC的内在神经机制，并结合脑疾病动物模型，研究神经-血管耦合状态与调节机制对静息态脑功能连接的影响。

静息态脑功能连接（RSFC）对于大脑功能的维持起着非常重要的作用，但是这种基于血液动力学信号的RSFC（hRSFC）潜在的神经机制以及神经-血管耦合状态对其影响还不清楚。针对这些问题，本项目建立了一套具备荧光校正功能的多模式光学成像系统，联合采用神经电活动光学成像和血液动力学光学成像技术在实验动物上开展静息态脑功能连接研究，提出了一种基于密度中心的快速聚类（DCBFC）并具有自适应阈值的静息态脑功能连接分析方法，可对大脑皮层进行快速聚类；分析比较了由不同频率神经信号得到的nRSFC与基于血液动力学信号的hRSFC的空间模式；研究了不同麻醉深度下大脑连通性的改变，随着麻醉深度增加，静息态脑功能连接强度会减小；在皮层扩散性抑制（CSD）引起的神经血管不耦合条件下，小鼠双侧皮层之间的相关性显著减小，而同侧皮层区域之间的相关性增加，进一步对CSD模型小鼠进行感觉刺激，其大脑皮层响应也发生改变；初步分析了不同类型神经元的静息态脑功能连接。本项目探讨静息态脑功能连接的内在神经机制及其影响因素，为利用该方法进行脑疾病早期诊断与疗效评估提供理论依据。