Modeling Structural Brain Connectivity

Abstract

The human brain consists of a gigantic complex network of interconnected neurons. Together all these connections determine who we are, how we react and how we interpret the world. Knowledge about how the brain is connected can further our understanding of the brain’s structural organization, help improve diagnosis, and potentially allow better treatment of a wide range of neurological disorders.Tractography based on diffusion magnetic resonance imaging is a unique tool to estimate this “structural connectivity” of the brain non-invasively and in vivo. During the last decade, brain connectivity has increasingly been analyzed using graph theoretic measures adopted from network science and this characterization of the brain’s structural connectivity has been shown to be useful for the classification of populations, such as healthy and diseased subjects. The structural connectivity of the brain estimated using tractography is, however, derived by integrating noisy estimates of the local fiber orientation in each voxel, entailing biases and limitations in the estimated connections and resulting in noisy graphs.In this thesis, the ability of stochastic block models to extract the latent organization of structural brain connectivity graphs is investigated. It is found that both the stochastic block model and its non-parametric extension, the infinite relational model, are able to reliably extract a clustering that better accounts for structural connectivity than cortical atlases based solely upon surface morphology. Furthermore, a statistical prediction framework to quantify the ability of a cortical parcellation to account for structural connectivity is proposed. It is tested on two commonly used cortical atlases that are both based on surface morphology, as well as on a recently proposed cortical parcellation by Glasser et al. (2016) that is based on both task and resting-state functional magnetic resonance imaging, cortical thickness and myelin. It is found that all three atlases capture the structural connectivity much better than random, but also that the parcellation based on multiple modalities is superior to those solely based on surface morphology.The generation of structural brain connectivity graphs comprises a comprehensive processing pipeline, with various experimenter-defined parameters. The settings of these parameters are, however, unclear and this subjective aspect complicates the cross-comparison of studies investigating structural brain connectivity derived from tractography. Even though scan acquisition parameters, i.e. spatial resolution, angular resolution and b-value, are often discussed as possible factors influencing the final result, the impact of these factors on the derived structural connectivity graph has not yet been investigated. Herein, structural connectivity graphs, generated using different combinations of the three aforementioned acquisition parameters, are validated by comparison to a connectivity graph derived using invasive tracer injections in monkeys. It is found that the choice of acquisition parameters influences the derived structural connectivity graph and that higher angular resolution is always beneficial. Surprisingly, it is also found that higher spatial resolution does not improve the derived graph, but further investigation is needed to confirm this result