A distribution-aware, information-theoretic measure of effective connectivity based on channel capacity under general residual distributions based on normalizing flows is introduced, and a principled distribution-aware framework for effective-connectivity estimation beyond Gaussian residual modeling is established.
Abstract
Effective-connectivity estimation from brain signals often relies on Gaussian residual modeling, which enables tractable estimation but can discard informative distributional structure and distort inferred directed interactions when empirical residuals are non-Gaussian. We show across multiple modalities, species, and experimental conditions that both brain signals and fitted channel residuals frequently deviate from Gaussianity. We therefore introduce a distribution-aware, information-theoretic measure of effective connectivity based on channel capacity under general residual distributions. To estimate the resulting capacity from empirical, potentially non-Gaussian residuals, we develop a dual-flow min-max estimator based on normalizing flows, in which a generator searches over admissible input distributions under a power constraint while an observer estimates output entropy. We provide a theoretical characterization of the estimator, showing that the observer objective recovers differential entropy up to a KL approximation term, that the formulation reduces to classical Gaussian capacity as a special case, and that residual entropy can alter achievable information rates beyond variance; game-gap and error analyses further characterize optimization and approximation sources. In brain-like simulations with known directed connectivity, Dual-flow achieves the highest AUROC and AUPRC across ten conditions spanning diverse network topologies, hidden drivers, feedback, and heterogeneous hemodynamics, compared with Gaussian capacity, Granger causality, VAR-LiNGAM, and GIMME. Applied to multimodal brain signals, the method reveals time- and condition-resolved directed interactions consistent with known neurobiological circuitry. Together, these results establish a principled distribution-aware framework for effective-connectivity estimation beyond Gaussian residual modeling.
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