Bayesian Estimation of Conditional Independence Graphs Improves Functional Connectivity Estimates

Functional connectivity concerns the correlated activity between neuronal populations in spatially segregated regions of the brain, which may be studied using functional magnetic resonance imaging (fMRI). This coupled activity is conveniently expressed using covariance, but this measure fails to distinguish between direct and indirect effects. A popular alternative that addresses this issue is partial correlation, which regresses out the signal of potentially confounding variables, resulting in a measure that reveals only direct connections. Importantly, provided the data are normally distributed, if two variables are conditionally independent given all other variables, their respective partial correlation is zero. In this paper, we propose a probabilistic generative model that allows us to estimate functional connectivity in terms of both partial correlations and a graph representing conditional independencies. Simulation results show that this methodology is able to outperform the graphical LASSO, which is the de facto standard for estimating partial correlations. Furthermore, we apply the model to estimate functional connectivity for twenty subjects using resting-state fMRI data. Results show that our model provides a richer representation of functional connectivity as compared to considering partial correlations alone. Finally, we demonstrate how our approach can be extended in several ways, for instance to achieve data fusion by informing the conditional independence graph with data from probabilistic tractography. As our Bayesian formulation of functional connectivity provides access to the posterior distribution instead of only to point estimates, we are able to quantify the uncertainty associated with our results. This reveals that while we are able to infer a clear backbone of connectivity in our empirical results, the data are not accurately described by simply looking at the mode of the distribution over connectivity. The implication of this is that deterministic alternatives may misjudge connectivity results by drawing conclusions from noisy and limited data.Author Summary: Significant neuroscientific effort is devoted to elucidating functional connectivity between spatially segregated brain regions. This requires that we are able to quantify the degree of dependence between the signals of different areas. Yet how this must be accomplished—using which measures, each with their own limitations and interpretations—is far from a trivial task. One frequently advocated metric for functional connectivity is partial correlation, which is related to conditional independence: if two regions are independent, conditioned on all other regions, then their partial correlation is zero, assuming Gaussian data. Here, we use a probabilistic generative model to describe the relationship between functional connectivity and conditional independence. We apply this Bayesian approach to reveal functional connectivity between subcortical areas, and in addition we propose different variants of the generative model for connectivity. In the first, we address how a Bayesian formulation of connectivity allows for integration with other imaging modalities, resulting in data fusion. Secondly, we show how prior constraints can be incorporated in our estimates of connectivity.