BrainIB++: Leveraging graph neural networks and information bottleneck for functional brain biomarkers in schizophrenia

The development of diagnostic models is gaining traction in the field of psychiatric disorders. Recently, machine learning classifiers based on resting-state functional magnetic resonance imaging (rs-fMRI) have been developed to identify brain biomarkers that differentiate psychiatric disorders from healthy controls. However, conventional machine learning-based diagnostic models often depend on extensive feature engineering, which introduces bias through manual intervention. While deep learning models are expected to operate without manual involvement, their lack of interpretability poses significant challenges in obtaining explainable and reliable brain biomarkers to support diagnostic decisions, ultimately limiting their clinical applicability. In this study, we introduce an end-to-end innovative graph neural network framework named BrainIB++, which applies the information bottleneck (IB) principle to identify the most informative data-driven brain regions as subgraphs during model training for interpretation. We evaluate the performance of our model against nine established brain network classification methods across three multi-cohort schizophrenia datasets. It consistently demonstrates superior diagnostic accuracy and exhibits generalizability to unseen data. Furthermore, the subgraphs identified by our model also correspond with established clinical biomarkers in schizophrenia, particularly emphasizing abnormalities in the visual, sensorimotor, and higher cognition brain functional network. This alignment enhances the model’s interpretability and underscores its relevance for real-world diagnostic applications. The code of our BrainIB++ is available at https://github.com/TianzhengHU/BrainIB_coding/tree/main/BrainIB_GIB.