Multivariate dynamical systems-based estimation of causal brain interactions in fMRI: Group-level validation using benchmark data, neurophysiological models and human connectome project data.

BACKGROUND Causal estimation methods are increasingly being used to investigate functional brain networks in fMRI, but there are continuing concerns about the validity of these methods. NEW METHOD Multivariate dynamical systems (MDS) is a state-space method for estimating dynamic causal interactions in fMRI data. Here we validate MDS using benchmark simulations as well as simulations from a more realistic stochastic neurophysiological model. Finally, we applied MDS to investigate dynamic casual interactions in a fronto-cingulate-parietal control network using human connectome project (HCP) data acquired during performance of a working memory task. Crucially, since the ground truth in experimental data is unknown, we conducted novel stability analysis to determine robust causal interactions within this network. RESULTS MDS accurately recovered dynamic causal interactions with an area under receiver operating characteristic (AUC) above 0.7 for benchmark datasets and AUC above 0.9 for datasets generated using the neurophysiological model. In experimental fMRI data, bootstrap procedures revealed a stable pattern of causal influences from the anterior insula to other nodes of the fronto-cingulate-parietal network. COMPARISON WITH EXISTING METHODS MDS is effective in estimating dynamic causal interactions in both the benchmark and neurophysiological model based datasets in terms of AUC, sensitivity and false positive rates. CONCLUSIONS Our findings demonstrate that MDS can accurately estimate causal interactions in fMRI data. Neurophysiological models and stability analysis provide a general framework for validating computational methods designed to estimate causal interactions in fMRI. The right anterior insula functions as a causal hub during working memory.