Large-scale dynamics of the brain are routinely modelled using systems of nonlinear dynamical equations that describe the evolution of population-level activity, with distinct neural populations often coupled according to an empirically measured structural connectivity matrix. This modelling approach has been used to generate insights into the neural underpinnings of spontaneous brain dynamics, as recorded with techniques such as resting state functional MRI (fMRI). In fMRI, researchers have many degrees of freedom in the way that they can process the data and recent evidence indicates that the choice of pre-processing steps can have a major effect on empirical estimates of functional connectivity. However, the potential influence of such variations on modelling results are seldom considered. Here we show, using three popular whole-brain dynamical models, that different choices during fMRI preprocessing can dramatically affect model fits and interpretations of findings. Critically, we show that the ability of these models to accurately capture patterns in fMRI dynamics is mostly driven by the degree to which they fit global signals rather than interesting sources of coordinated neural dynamics. We show that widespread deflections can arise from simple global synchronisation. We introduce a simple two-parameter model that captures these fluctuations and performs just as well as more complex, multi-parameter biophysical models. From our combined analyses of data and simulations, we describe benchmarks to evaluate model fit and validity. Although most models are not resilient to denoising, we show that relaxing the approximation of homogeneous neural populations by more explicitly modelling inter-regional effective connectivity can improve model accuracy at the expense of increased model complexity. Our results suggest that many complex biophysical models may be fitting relatively trivial properties of the data, and underscore a need for tighter integration between data quality assurance and model development.
Keywords: Connectivity; Connectome; Denoising; DiCER; GSR; Modelling; Network; Resting-state; fMRI; rsfMRI.
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