Model-based whole-brain effective connectivity to study distributed cognition in health and disease

Neuroimaging techniques are now widely used to study human cognition. The functional associations between brain areas have become a standard proxy to describe how cognitive processes are distributed across the brain network. Among the many analysis tools available, dynamic models of brain activity have been developed to overcome the limitations of original connectivity measures such as functional connectivity. This goes in line with the many efforts devoted to the assessment of directional interactions between brain areas from the observed neuroimaging activity. This opinion article provides an overview of our model-based whole-brain effective connectivity to analyze fMRI data, while discussing the pros and cons of our approach with respect to other established approaches. Our framework relies on the multivariate Ornstein-Uhlenbeck (MOU) process and is thus referred to as MOU-EC. Once tuned, the model provides a directed connectivity estimate that reflects the dynamical state of BOLD activity, which can be used to explore cognition. We illustrate this approach using two applications on task-evoked fMRI data. First, as a connectivity measure, MOU-EC can be used to extract biomarkers for task-specific brain coordination, understood as the patterns of areas exchanging information. The multivariate nature of connectivity measures raises several challenges for whole-brain analysis, for which machine-learning tools present some advantages over statistical testing. Second, we show how to interpret changes in MOU-EC connections in a collective and model-based manner, bridging with network analysis. Our framework provides a comprehensive set of tools that open exciting perspectives to study distributed cognition, as well as neuropathologies. Author SummaryBrain connectivity measures have been increasingly used to study cognition and neuropathologies with neuroimaging data. Many methods have been developed with particular objectives, in particular predictability to obtain biomarkers (i.e., which brain regions exhibit changes in their interactions across conditions) and interpretability (relating the connectivity measures back to the biology). In this article we present our framework for whole-brain effective connectivity that aims to find the equilibrium between these two desired properties, relying on a dynamic model that can be fitted to fMRI time series. Meanwhile, we compare it with previous work. Concretely, we show how machine learning can be used to extract biomarkers and how network-oriented analysis can be used to interpret the model estimates in terms of brain dynamics.