Heterogeneity Analysis on Multi-State Brain Functional Connectivity and Adolescent Neurocognition

Brain functional connectivity or connectome, a unique measure for brain functional organization, provides a great potential to explain the neurobiological underpinning of behavioral profiles. Existing connectome-based analyses highly concentrate on brain activities under a single cognitive state, and fail to consider heterogeneity when attempting to characterize brain-to-behavior relationships. In this work, we study the complex impact of multi-state functional connectivity on behaviors by analyzing the data from a recent landmark brain development and child health study. We propose a nonparametric, Bayesian supervised heterogeneity analysis to uncover neurodevelopmental subtypes with distinct effect mechanisms. We impose stochastic block structures to identify network-based functional phenotypes and develop a variational expectation-maximization algorithm to facilitate an efficient posterior computation. Through integrating resting-state and task-related functional connectomes, we dissect heterogeneous effect mechanisms on children’s fluid intelligence from the functional network phenotypes, including Fronto-parietal Network and Default Mode Network, under different cognitive states. Based on extensive simulations, we further confirm the superior performance of our method on uncovering brain-to-behavior relationships. Supplementary materials for this article are available online including a standardized description of the materials available for reproducing the work.