Higher-Order Triadic Interactions: Insights Into the Multiscale Network Organization in Schizophrenia

Complex biological systems, like the brain, exhibit intricate multiway and multiscale interactions that drive emergent behaviors. In psychiatry, neural processes extend beyond pairwise connectivity, involving higher-order interactions critical for understanding mental disorders. Conventional brain network studies focus on pairwise links, offering insights into basic connectivity but failing to capture the complexity of neural dysfunction in psychiatric conditions. This study seeks to address this gap by utilizing a matrix-based entropy functional for estimating total correlation, which serves as a mathematical framework for capturing multivariate information. We apply this framework to fMRI-ICA-derived multiscale brain networks, enabling the investigation of multivariate interaction patterns within the human brain across multiple scales. Additionally, this approach holds significant promise for psychiatric research on schizophrenia, offering a novel framework for investigating higher-order triadic brain network interactions associated with the disorder. By examining both triple interactions and the latent factors underlying the triadic relationships among intrinsic brain connectivity networks through tensor decomposition, our study presents a novel approach to understanding changes in higher-order brain networks in schizophrenia. This framework not only advances our understanding of complex brain functions but also opens new avenues for investigating the pathophysiology of schizophrenia, potentially informing more targeted diagnostic and therapeutic strategies. Moreover, this method for analyzing multiway interactions is applicable across signal analysis domains. In this study, we apply this approach to neural signals in schizophrenia, demonstrating its ability to reveal complex multiway interaction patterns and provide new insights into brain connectivity beyond traditional pairwise analyses in the context of brain disorders.