Modelling the mechanisms underlying variable spatiotemporal cortical response dynamics

Abstract

Elucidating how the brain's diverse repertoire of neural dynamics emerges from its fixed anatomical structure, known as the `structure--function relationship', remains a challenge in macroscale neuroscience. While progress has been made in predicting resting-state (spontaneous) functional connectivity from structural connectivity, this static paradigm often fails to capture the mechanisms that shape dynamics over faster (sub-second) timescales, or how the spatiotemporal properties of brain dynamics can reconfigure over time under a fixed structural connectome. Accordingly, this thesis investigates the mechanisms that underlie spatiotemporal variability in stimulus-evoked cortical dynamics over fast (sub-second) timescales. Its main contribution is a timely investigation into the open question of why the geometry of brain anatomy can successfully capture key statistical properties of spontaneous brain dynamics, while ignoring the highly specific arrangements of the various long-distance inter-regional fibres that support global brain communication. Specifically, this thesis demonstrates, through newly constructed models, that long-distance connectivity is essential for capturing fast-timescale interactions between specific remote populations, but these interactions are obscured in slower order-of-seconds fluctuations of spontaneous activity. Furthermore, these fast dynamics are shown to be contingent on the spatial proximity of the driving stimulus, and critically gated by the simultaneous burst-like firing of subcortical arousal nuclei, which is often ignored in the modelling literature. Collectively, this thesis challenges the notion of a fixed structure--function relationship, showing that brain dynamics over fast timescales, despite evolving on a static anatomical backbone, can exhibit a diverse range of spatiotemporal patterns, mediated by variations in the spatial profile of driving stimuli, and fluctuations in internal arousal.