Grant: CIHR Fellowship

Functional Magnetic Resonance Imaging (fMRI) is the most widely used technique for measuring dynamic neuronal activity across the whole brain with no harmful effects, making it an invaluable tool for human neuroscience. FMRI measurements are based on tracking focal changes in blood flow and oxygenation that occur during brain activity to meet energetic demand. Because fMRI is, therefore, an indirect measure of neuronal activity, the confidence with which changes in neuronal activity can be inferred is limited. The hypothesis of this study is that a more complete picture of the blood vessels in the brain, and how they react to brain activity, will help us to better interpret the fMRI signals. New evidence from microscopy studies in rodents indicates that the control of blood flow in response to neuronal activity is far more precise than previously believed, suggesting that fMRI has the potential to be a reliable marker of neuronal activity if measured and interpreted correctly. However, it is challenging to translate these findings to humans since the organization of rodent blood vessels is markedly different from ours. This project will create a 3D reconstruction of the blood vessel network-down to the smallest capillaries-from human brain specimens, from which a model of how the vessels react to neuronal firing to control blood delivery will be generated-and from this, how the fMRI signals change in response to brain activity. To ensure accuracy, the model will be validated against high-resolution human fMRI data acquired on an ultra-high magnetic field strength MRI scanner. This bottom-up approach will provide a crucial missing link between measured fMRI signals and the detailed underlying physiology, helping to better understand fMRI signals and improve our ability to accurately measure brain function.