The activity of functional brain networks is responsible for the emergence of time-varying cognition and behaviour. Accordingly, time-varying correlations (Functional Connectivity) in resting fMRI have been shown to be predictive of behavioural traits, and psychiatric and neurological conditions. Typically, methods that measure time-varying Functional Connectivity (FC), such as sliding windows approaches, do not separately model when changes occur in the mean activity levels from when changes occur in the FC, therefore conflating these two distinct types of modulation. We show that this can bias the estimation of time-varying FC to appear more stable over time than it actually is. Here, we propose an alternative approach that models changes in the mean brain activity and in the FC as being able to occur at different times to each other. We refer to this method as the Multi-dynamic Adversarial Generator Encoder (MAGE) model, which includes a model of the network dynamics that captures long-range time dependencies, and is estimated on fMRI data using principles of Generative Adversarial Networks. We evaluated the approach across several simulation studies and resting fMRI data from the Human Connectome Project (1003 subjects), as well as from UK Biobank (13301 subjects). Importantly, we find that separating fluctuations in the mean activity levels from those in the FC reveals much stronger changes in FC over time, and is a better predictor of individual behavioural variability
Accurate temporal modelling of functional brain networks is essential in the quest for understanding how such networks facilitate cognition. Researchers are beginning to adopt time-varying analyses for electrophysiological data that capture highly dynamic processes on the order of milliseconds. Typically, these approaches, such as clustering of functional connectivity profiles and Hidden Markov Modelling (HMM), assume mutual exclusivity of networks over time. Whilst a powerful constraint, this assumption may be compromising the ability of these approaches to describe the data effectively. Here, we propose a new generative model for functional connectivity as a time-varying linear mixture of spatially distributed statistical ''modes''. The temporal evolution of this mixture is governed by a recurrent neural network, which enables the model to generate data with a rich temporal structure. We use a Bayesian framework known as amortised variational inference to learn model parameters from observed data. We call the approach DyNeMo (for Dynamic Network Modes), and show using simulations it outperforms the HMM when the assumption of mutual exclusivity is violated. In resting-state MEG, DyNeMo reveals a mixture of modes that activate on fast time scales of 100-150 ms, which is similar to state lifetimes found using an HMM. In task MEG data, DyNeMo finds modes with plausible, task-dependent evoked responses without any knowledge of the task timings. Overall, DyNeMo provides decompositions that are an approximate remapping of the HMM's while showing improvements in overall explanatory power. However, the magnitude of the improvements suggests that the HMM's assumption of mutual exclusivity can be reasonable in practice. Nonetheless, DyNeMo provides a flexible framework for implementing and assessing future modelling developments.
Spectrum estimators that make use of averaging across time segments are ubiquitous across neuroscience. The core of this approach has not changed substantially since the 1960s, though many advances in the field of regression modelling and statistics have been made during this time. Here, we propose a new approach, the General Linear Model (GLM) Spectrum, which reframes time averaged spectral estimation as multiple regression. This brings several benefits, including the ability to do confound modelling, hierarchical modelling and significance testing via non-parametric statistics.We apply the approach to a first-level EEG resting-state dataset alternating between eyes open and eyes closed resting-state. The GLM-Spectrum can model both conditions, quantify their differences, and perform denoising through confound regression in a single step. This application is scaled up from a single channel to a whole-head recording and, finally, applied to quantify age differences across a large group-level dataset. We show that the GLM-Spectrum lends itself to rigorous modelling of within- and between-subject contrasts as well as their interactions, and that the use of model-projected spectra provides an intuitive visualisation. The GLM-Spectrum is a flexible framework for robust multi-level analysis of power spectra, with adaptive covariance and confound modelling.
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