Age-Related Changes in Human Anatomical and Functional Brain Networks

Thesis (Ph.D.) - Indiana University, Psychological and Brain Sciences, 2015i) The first component characterizes age-related changes in specific connections. We find that functional connections within and between intrinsic connectivity networks (ICNs) follow distinct lifespan trajectories. We further characterize these changes in terms of each ICN’s “modularity” and find that most ICNs become less modular (i.e. less segregated) with age. In anatomical networks we find that hub regions are disproportionately affected by age and become less efficiently connected to the rest of the brain. Finally, we find that, with age stronger functional connections are supported by longer (multi-step) anatomical pathways for communication. ii) The second component is concerned with characterizing age-related changes in the boundaries of ICNs. To this end we used a multi-layer variant of modularity maximization to decompose networks into modules at different organizational scales, which we find exhibit scale-specific trends with age. At coarse scales, for example, we find that modules become more segregated whereas modules defined at finer scales become less segregated. We also find that module composition changes with age, and specific areas associated with memory change their module allegiance with age. iii) In the final component we use generative models to uncover wiring rules for the anatomical brain networks. Modeling network growth as a spatial penalty combined with homophily, we find that we can generate synthetic networks with many of the same properties as real-world brain networks. Fitting this model to individuals, we show that the parameter governing the severity of the spatial penalty weakens monotonically with age and that the overall ability to reproduce realistic connectomes for older individuals suffers. These results suggest that, with age, additional constraints may play an important role in shaping the topology of brain structural networks