Bayesian subtyping for multi-state brain functional connectome with application on adolescent brain cognition

Abstract

Converging evidence indicates that the heterogeneity of cognitive profiles may arise through detectable alternations in brain functions. Particularly, brain functional connectivity, measured under resting and cognitive states, characterizes the unique neuronal interconnections across large-scale brain networks. Despite an unprecedented opportunity to uncover neurobiological subtypes through clustering or subtyping analyses on multi-state functional connectivity, few existing approaches are applicable here to accommodate the network topology and unique biological architecture of functional connectivity. To address this issue, we propose an innovative Bayesian nonparametric network-variate clustering analysis to uncover subgroups with homogeneous brain functional network patterns integrating different cognitive states. In light of the existing neuroscience literature, we assume there are unknown state-specific modular structures within functional connectivity and simultaneously impose selection to identify informative network features for defining subtypes within unsupervised learning. To further facilitate practical use, we develop a computationally efficient variational inference algorithm to perform posterior inference with satisfactory estimation accuracy. Extensive simulations show the superior clustering accuracy and plausible result of our method. Applying the method to the landmark Adolescent Brain Cognitive Development (ABCD) study, we successfully establish neurodevelopmental subtypes linked with impulsivity related behavior trait, and identify brain sub-network phenotypes under each state to signal neurobiological heterogeneity.