UCSF

Understanding how white matter pathways in the brain, or the structural connectome (SC), shape and constrain functional dynamics is a central problem in neuroscience known as the structure-function problem. Using diffusion MRI and functional MRI from large publicly available datasets, including the Human Connectome Project, I developed a framework for studying the graph Laplacian of the SC and its relationship to brain function. First, I investigated the group-level properties of graph Laplacian harmonics, including which are shared across subjects versus unique to individuals, and their relationships to resting-state brain organization. I found that these harmonics form an integration-to-segregation spectrum, in which the ends of the spectrum are shared across subjects and localize to sensory regions, whereas the center is more individualized and relates to multimodal brain regions. Second, to better understand how observed brain function embeds an underlying notion of SC, I developed a graph deconvolution method that models and removes the effect of passive signal diffusion through the SC. I found that the deconvolved signals exhibit remodeled functional connectivity, decoupled resting-state networks, and a disruption of the typical unimodal-multimodal functional divide. Finally, to investigate whether passive diffusion can be used to recover information about the SC itself, I developed a model that parsimoniously parameterizes directed SC using gene gradients and fits this model to brain function. I found that this directed SC model can estimate ground-truth directed SC across three non-human species---C. elegans, mouse, and macaque---and that the resulting human directed SC estimates are biologically plausible and predict a directed net flow that reproduces the original unimodal-multimodal functional divide. Together, these findings position the graph Laplacian of the SC as a scaffold for brain function and offer a principled framework for studying brain function through the lens of biological structure.