Spatial dynamics within and between brain functional domains: A hierarchical approach to study time-varying brain function.

The analysis of time-varying activity and connectivity patterns (i.e., the chronnectome) using resting-state magnetic resonance imaging has become an important part of ongoing neuroscience discussions. The majority of previous work has focused on variations of temporal coupling among fixed spatial nodes or transition of the dominant activity/connectivity pattern over time. Here, we introduce an approach to capture spatial dynamics within functional domains (FDs), as well as temporal dynamics within and between FDs. The approach models the brain as a hierarchical functional architecture with different levels of granularity, where lower levels have higher functional homogeneity and less dynamic behavior and higher levels have less homogeneity and more dynamic behavior. First, a high-order spatial independent component analysis is used to approximate functional units. A functional unit is a pattern of regions with very similar functional activity over time. Next, functional units are used to construct FDs. Finally, functional modules (FMs) are calculated from FDs, providing an overall view of brain dynamics. Results highlight the spatial fluidity within FDs, including a broad spectrum of changes in regional associations, from strong coupling to complete decoupling. Moreover, FMs capture the dynamic interplay between FDs. Patients with schizophrenia show transient reductions in functional activity and state connectivity across several FDs, particularly the subcortical domain. Activity and connectivity differences convey unique information in many cases (e.g., the default mode) highlighting their complementarity information. The proposed hierarchical model to capture FD spatiotemporal variations provides new insight into the macroscale chronnectome and identifies changes hidden from existing approaches.