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相互关联的功能区域的复杂网络。这种功能结构对每个人来说都是独一无二的，它的特征依赖于功能磁共振成像（fMRI），这是一种可以在高时空分辨率下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开展了研究项目，旨在确定最能解释大脑功能的功能磁共振成像特征。许多fMRI分析方法被设计用来检测功能连接，表征它们随时间的动态变化，并确定它们的方向性，即信息是否沿着给定的功能链接在首选方向上流动。这些方法显示出巨大的潜力，可以提高我们对大脑功能组织及其对认知行为的影响的理解。然而，功能磁共振成像只能间接反映大脑的神经元活动。FMRI测量的血氧变化仅仅是神经元放电的下游反应，FMRI对各种非神经元生理波动也很敏感。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正的潜在神经元连接的基础。更复杂的是，这种真正的神经元连接通常是无法获得的，这阻碍了fMRI连接测量的验证。因此，我建议使用与fMRI同时记录的健康脑区的颅内脑电图（iEEG）来测量真实的神经元连通性，这将作为改进和验证fMRI分析方法的金标准。我们的中心是世界上少数几个可以同时进行eeg - fmri记录的中心之一。与传统的头皮脑电图不同，iEEG提供了与fMRI相当的空间分辨率的局部神经元活动测量。此外，同时获取脑电图和功能磁共振成像将确保两种模式之间的动态连接波动可以匹配。我们的具体目标是：1。识别静态和动态功能连接下的局部电生理特征。2. 表征局部神经元活动与fMRI信号波动之间的血流动力学反应。3. 验证算法，推断fMRI连接的方向性。4. 建立高时间分辨率fMRI结合iEEG来确定高频连接波动的神经元基础。该研究项目将广泛影响对过去fMRI研究的解释，以及对未来分析的优化，这些分析旨在理解行为、认知和系统神经科学中的基本大脑过程。高素质的人才将在多模态功能神经成像的所有方法学方面接受培训，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.