A research program into the neuronal basis of functional connectivity

在宏观尺度上，人类大脑被组织成一个复杂的网络，由相互连接的功能区域组成。这种功能结构对每个人来说都是独特的，其特征依赖于功能性磁共振成像（fMRI），这是一种可以以高时空分辨率监测大脑活动的神经成像方式。近年来，我的实验室和其他几个实验室已经开发了一些研究项目，旨在确定能够最好地解释大脑功能的功能磁共振成像特征。许多功能磁共振成像分析方法已被设计用于检测功能连接，表征其随时间的动态变化，并确定其方向性，即信息是否沿沿着给定的功能链接以优选的方向流动。这些方法显示出巨大的潜力，以提高我们的大脑的功能组织及其对认知行为的影响的理解。然而，fMRI只能间接反映大脑的神经元活动。功能磁共振成像测量血氧的变化，这仅仅是对神经元放电的下游反应，并且功能磁共振成像还对各种非神经元生理波动敏感。因此，从功能磁共振成像中提取的任何功能连接测量都可能没有真实的神经元连接基础。使这个问题更加复杂的是，这种真正的神经元连接通常是不可访问的，排除了功能磁共振成像连接措施的验证。因此，我建议使用颅内脑电图（iEEG）记录从健康的大脑区域，同时与功能磁共振成像测量真正的神经元连接，这将作为一个金标准，以改善和验证功能磁共振成像分析方法。我们的中心是世界上少数可以同时进行iEEG-fMRI记录的中心之一。与传统的头皮EEG不同，iEEG提供了与fMRI相当的空间分辨率的神经元活动的局部测量。此外，iEEG和fMRI的同时采集将确保动态连接波动可以在两种模式之间匹配。我们的具体目标是：1。识别静态和动态功能连接的局部电生理特征。2.描述血流动力学反应，将局部神经元活动与fMRI信号波动联系起来。3.推理功能磁共振成像连接方向性的算法。4.建立高时间分辨率fMRI结合iEEG，以确定高频连接波动的神经元基础。这项研究计划将对过去的功能磁共振成像研究的解释和未来分析的优化产生广泛的影响，旨在了解行为，认知和系统神经科学中的基本大脑过程。高素质的人员将在多模式功能神经成像的所有方法学方面进行培训，为加拿大未来的神经科学和神经成像研究提供坚实的专业知识。

At a macroscopic scale, the human brain is organized into a complex network of interconnected functional areas. This functional architecture is unique to each person and its characterization relies on functional magnetic resonance imaging (fMRI), a neuroimaging modality that can monitor brain activity at high spatiotemporal resolutions. In recent years, my lab and several others have developed research programs aiming to identify fMRI features that can best explain brain function. Numerous fMRI analysis methods have been designed to detect functional connections, characterize their dynamic variability over time, and determine their directionality, i.e. whether information is flowing in a preferred direction along a given functional link. These methods show immense potential to improve our understanding of the functional organization of the brain and its effect on cognitive behaviour. However, fMRI only indirectly reflects the neuronal activity of the brain. FMRI measures alterations in blood oxygenation that are merely a downstream response to neuronal firing, and fMRI is also sensitive to various non-neuronal physiological fluctuations. Therefore, any functional connectivity measure extracted from fMRI could conceivably have no basis in the true underlying neuronal connectivity. Compounding this issue is that this true neuronal connectivity is generally not accessible, precluding the validation of fMRI connectivity measures. I thus propose to use intracranial electroencephalography (iEEG) recorded from healthy brain areas simultaneously with fMRI to measure true neuronal connectivity, which will serve as a gold standard to improve and validate fMRI analysis methods. Our center is one of a handful in the world where simultaneous iEEG-fMRI recordings can be performed. Unlike conventional scalp EEG, iEEG provides local measurements of neuronal activity at spatial resolutions comparable to fMRI. Moreover, the simultaneous acquisitions of iEEG and fMRI will ensure that dynamic connectivity fluctuations can be matched between both modalities. Our specific objectives are then to: 1. Identify local electrophysiological signatures underlying static and dynamic functional connectivity. 2. Characterize the hemodynamic response linking local neuronal activity to fMRI signal fluctuations. 3. Validate algorithms that infer the directionality of fMRI connections. 4. Establish high temporal resolution fMRI combined with iEEG to determine the neuronal basis of high-frequency connectivity fluctuations. This research program will have widespread implications on the interpretation of past fMRI studies and on the optimization of future analyses aimed at understanding fundamental brain processes in behavioural, cognitive, and systems neuroscience. Highly qualified personnel will be trained in all methodological aspects of multimodal functional neuroimaging, providing solid expertise for future neuroscience and neuroimaging research in Canada.