An in vivo investigation of short-ranged structural connectivity in the human brain
Abstract
Short-ranged connectivity comprise the majority of connections throughout the brain, joining together nearby regions and contributing to important networks that facilitate complex function and cognition. Despite constituting the majority of white matter in the brain and their importance, studies examining short-ranged connections have thus far been limited in part due to the challenges associated with identifying and validating them. Tractography, a computational technique for reconstructing axon trajectories from diffusion magnetic resonance imaging, has been commonly used to identify and study major white connections (e.g. corticospinal tract), which are easier to identify relative to the short-ranged connections. The use of additional constraints (e.g. geometry, regions of interest) together with tractography has enabled the ability to identify short-ranged connections of interest, such as the ”U”-shaped tracts residing just below the cortical surface, and the subcortical connectome tracts found in the deep brain.
In this thesis, we aimed to quantify the reliability of such techniques for studying the short- ranged connections and applied them to examine changes to short-ranged connectivity in patients with first episode schizophrenia. First, the reliability of identifying short-ranged, ”U”- shaped tracts is examined in Chapter 1, leveraging geometric constraints for identifying the ”U”-shaped geometry together with clustering techniques to establish distinct tracts. Here, we two different clustering techniques, applying them to two datasets to study both the reliability of identifying short-ranged, ”U”-shaped tracts across different subjects and in a single individual (across different sessions). In Chapter 2, the reliability for identifying the subcortical connectome (short-ranged connections between subcortical structures) is evaluated. Connectivity of the deep brain is often hard to recapitulate due to the multiple orientations contributing to com- plex diffusion signals. Thus, we leveraged regions of interests determined through histological data to aid identification of the short-ranged connections in the compact region. Finally, Chapter 4, uses the techniques from chapter 2 in combination with quantitative measures sensitive to microstructural changes to study changes to short-ranged, ”U”-shaped tracts in the frontal lobes of patients with first-episode schizophrenia (FES). By studying the short-ranged connections in patients with FES, biomarkers associated with clinical presentation may be elucidated and may aid the current understanding to improve future treatment. Overall, the projects presented here quantify the reliability of current techniques for investigating short-ranged connectivity and provides a framework for evaluating of future techniques. Additionally, the techniques evaluated here can be used to elucidate new findings and improve treatment in clinical popula- tions.