Whole-brain causal discovery using fMRI

Despite significant research, discovering causal relationships from fMRI remains a challenge. Popular methods such as Granger causality and dynamic causal modeling fall short in handling contemporaneous effects and latent common causes. Methods from causal structure learning literature can address these limitations but often scale poorly with network size and need acyclicity. In this study, we first provide a taxonomy of existing methods and compare their accuracy and efficiency on simulated fMRI from simple topologies. This analysis demonstrates a pressing need for more accurate and scalable methods, motivating the design of Causal discovery for Large-scale Low-resolution Time-series with Feedback (CaLLTiF). CaLLTiF is a constraint-based method that uses conditional independence between contemporaneous and lagged variables to extract causal relationships. On simulated fMRI from the macaque connectome, CaLLTiF achieves significantly higher accuracy and scalability than all tested alternatives. From resting-state human fMRI, CaLLTiF learns causal connectomes that are highly consistent across individuals, show clear top-down flow of causal effect from attention and default mode to sensorimotor networks, exhibit Euclidean distance dependence in causal interactions, and are highly dominated by contemporaneous effects. Overall, this work takes a major step in enhancing causal discovery from whole-brain fMRI and defines a new standard for future investigations.