Recent precision functional mapping of individual human brains has shown that individual brain organization is qualitatively different from group average estimates and that individuals exhibit distinct brain network topologies. How this variability affects the connectivity within individual resting-state networks remains an open question. This is particularly important since certain resting-state networks such as the default mode network (DMN) and the fronto-parietal network (FPN) play an important role in the early detection of neurophysiological diseases like Alzheimer’s, Parkinson’s, and attention deficit hyperactivity disorder. Using different types of similarity measures including conditional mutual information, we show here that the backbone of the functional connectivity and the direct connectivity within both the DMN and the FPN does not vary significantly between healthy individuals for the AAL brain atlas. Weaker connections do vary however, having a particularly pronounced effect on the cross-connections between DMN and FPN. Our findings suggest that the link topology of single resting-state networks is quite robust if a fixed brain atlas is used and the recordings are sufficiently long—even if the whole brain network topology between different individuals is variable.

Maximum entropy estimation is of broad interest for inferring properties of systems across many disciplines. Using a recently introduced technique for estimating the maximum entropy of a set of random discrete variables when conditioning on bivariate mutual informations and univariate entropies, we show how this can be used to estimate the direct network connectivity between interacting units from observed activity. As a generic example, we consider phase oscillators and show that our approach is typically superior to simply using the mutual information. In addition, we propose a nonparametric formulation of connected informations, used to test the explanatory power of a network description in general. We give an illustrative example showing how this agrees with the existing parametric formulation, and demonstrate its applicability and advantages for resting-state human brain networks, for which we also discuss its direct effective connectivity. Finally, we generalize to continuous random variables and vastly expand the types of information-theoretic quantities one can condition on. This allows us to establish significant advantages of this approach over existing ones. Not only does our method perform favorably in the undersampled regime, where existing methods fail, but it also can be dramatically less computationally expensive as the cardinality of the variables increases.