A research program into the neuronal basis of functional connectivity

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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.