Circular inference predicts nonuniform overactivation and dysconnectivity in brain-wide connectomes

Schizophr Res. 2021 Feb 19;S0920-9964(21)00031-1. doi: 10.1016/j.schres.2020.12.045. Online ahead of print.


Schizophrenia is a severe mental disorder whose neural basis remains difficult to ascertain. Among the available pathophysiological theories, recent work has pointed towards subtle perturbations in the excitation-inhibition (E/I) balance within different neural circuits. Computational approaches have suggested interesting mechanisms that can account for both E/I imbalances and psychotic symptoms. Based on hierarchical neural networks propagating information through a message-passing algorithm, it was hypothesized that changes in the E/I ratio could cause a "circular belief propagation" in which bottom-up and top-down information reverberate. This circular inference (CI) was proposed to account for the clinical features of schizophrenia. Under this assumption, this paper examined the impact of CI on network dynamics in light of brain imaging findings related to psychosis. Using brain-inspired graphical models, we show that CI causes overconfidence and overactivation most specifically at the level of connector hubs (e.g., nodes with many connections allowing integration across networks). By also measuring functional connectivity in these graphs, we provide evidence that CI is able to predict specific changes in modularity known to be associated with schizophrenia. Altogether, these findings suggest that the CI framework may facilitate behavioral and neural research on the multifaceted nature of psychosis.

Keywords: Belief; Circular; Connectome; Graph; Inference; Schizophrenia.