Comparison of fluctuations in global network topology of modeled and empirical brain functional connectivity

Dynamic models of large-scale brain activity have been used for reproducing many empirical findings on human brain functional connectivity. Features that have been shown to be reproducible by comparing modeled to empirical data include functional connectivity measured over several minutes of resting-state functional magnetic resonance imaging, as well as its time-resolved fluctuations on a time scale of tens of seconds. However, comparison of modeled and empirical data has not been conducted yet for fluctuations in global network topology of functional connectivity, such as fluctuations between segregated and integrated topology or between high and low modularity topology. Since these global network-level fluctuations have been shown to be related to human cognition and behavior, there is an emerging need for clarifying their reproducibility with computational models. To address this problem, we directly compared fluctuations in global network topology of functional connectivity between modeled and empirical data, and clarified the degree to which a stationary model of spontaneous brain dynamics can reproduce the empirically observed fluctuations. Modeled fluctuations were simulated using a system of coupled phase oscillators wired according to brain structural connectivity. By performing model parameter search, we found that modeled fluctuations in global metrics quantifying network integration and modularity had more than 80% of magnitudes of those observed in the empirical data. Temporal properties of network states determined based on fluctuations in these metrics were also found to be reproducible, although their spatial patterns in functional connectivity did not perfectly matched. These results suggest that stationary models simulating resting-state activity can reproduce the magnitude of empirical fluctuations in segregation and integration, whereas additional factors, such as active mechanisms controlling non-stationary dynamics and/or greater accuracy of mapping brain structural connectivity, would be necessary for fully reproducing the spatial patterning associated with these fluctuations.Author summary: In human neuroscience, there is growing interest in temporal fluctuations in coactivation patterns of resting-state brain activity. To elucidate generative mechanisms of these fluctuations, theoretical studies try to reproduce their empirical properties by simulations using dynamic models of large-scale spontaneous brain activity. However, evaluations of the reproducibility have not been extended so far to the fluctuations in global network topology of coactivation patterns, recently shown to be related to human cognition and behavior. Here we examine the extent to which a stationary model typically used for simulating resting-state activity can reproduce spatial and temporal patterns of the empirically observed fluctuations in global network topology. We found that such a model successfully reproduced the magnitude of empirical fluctuations as well as their temporal dynamics, whereas their spatial patterning was not fully accounted for by the simulation. Our results suggest that stationary models can explain many empirical properties in the fluctuations in global network topology, while modeling of non-stationary dynamics and/or greater estimation accuracy of anatomical connections underlying the simulation would be required for complete replication. This finding provides new insights into how fluctuations in global network topology of coactivation patterns emerge in the human brain.