Modeling Higher-Order Brain Interactions via a Multi-View Information Bottleneck Framework for fMRI-based Psychiatric Diagnosis
Authors: Kunyu Zhang, Qiang Li, Vince D. Calhoun, Shujian Yu
Organizations: Department of Computer Science, Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, The Netherlands · Tri-Institutional Center for Translational Research in Neuroimaging and Data Science (TReNDS), Georgia State University, Georgia Institute of Technology, and Emory University, Atlanta, GA, 30303, USA · Department of Physics and Technology, UiT - The Arctic University of Norway, Tromsø, 9019, Norway
Resting-state functional magnetic resonance imaging (fMRI) has emerged as a cornerstone for psychiatric diagnosis, yet most approaches rely on pairwise brain cortical or sub-cortical connectivities that overlooks higher-order interactions (HOIs) central to complex brain dynamics. While hypergraph methods encode HOIs through predefined hyperedges, their construction typically relies on heuristic similarity metrics and does not explicitly characterize whether interactions are synergy- or redundancy-dominated. In this paper, we introduce O-information, a signed measure that characterizes the informational nature of HOIs, and integrate third- and fourth-order O-information into a unified multi-view information bottleneck framework for fMRI-based psychiatric diagnosis. To enable scalable O-information estimation, we further develop two independent acceleration strategies: a Gaussian analytical approximation and a randomized matrix-based Rényi entropy estimator, achieving over a 30-fold computational speedup compared with conventional estimators. Our tri-view architecture systematically fuses pairwise, triadic, and tetradic brain interactions, capturing comprehensive brain connectivity while explicitly penalizing redundancy. Extensive evaluation across four benchmark datasets (REST-meta-MDD, ABIDE, UCLA, ADNI) demonstrates consistent improvements, outperforming 11 baseline methods including state-of-the-art graph neural network (GNN) and hypergraph based approaches. Moreover, our method reveals interpretable region-level synergy-redundancy patterns which are not explicitly characterized by conventional hypergraph formulations.
Understanding complex interactions between brain regions is critical for early neurodegenerative disease classification such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). While graph-based models are widely used to analyze brain networks, most existing approaches primarily focus on pairwise interactions between directly connected nodes, limiting their ability to capture higher-order dependencies across multiple regions. Although hypergraph-based methods have been proposed to model higher-order relations, many rely on predefined hyperedges or restrict learning to hyperedge weights, reducing flexibility and limiting their capacity to capture multi-resolution structural patterns. In this regard, we introduce an adaptive multi-scale hyperedge learning framework, i.e., MuHL, which constructs hierarchical node features and dynamically learns high-order interactions through continuous hyperedge construction over multi-resolution graph signals. Extensive experiments on multiple brain network benchmarks demonstrate that MuHL consistently improves disease classification performance across different stages, and further identifies key regions of interest (ROIs) and their group-wise interactions from the learned hyperedges that are associated with disease progression, highlighting its potential as a powerful tool for brain network analysis in neurodegenerative disorders.
Functional brain networks exhibit a hierarchical organization across ROI, community, and whole-brain levels, supporting local processing, inter-community coordination, and global integration. Recent studies have demonstrated that brain community-aware modeling is beneficial for both diagnosis and biomarker identification of brain networks. However, existing brain graph modeling methods often struggle to model ROI-community interactions, thereby failing to fully exploit the hierarchy across ROI, community, and whole-brain network levels. To address this issue, inspired by deep hyperbolic learning in modeling hierarchical structures, we propose a novel framework, termed Hyperbolic Learning on Brain Graphs (HLBG), for brain network analysis. The core idea of HLBG is to exploit the inherent hierarchical geometry of hyperbolic space to model the hierarchical relationships among ROIs, functional communities, and the whole-brain network, thereby learning hierarchy-aware and highly discriminative representations for brain network data. Specifically, HLBG first projects representations from ROIs, communities, and the whole-brain network into Lorentzian hyperbolic space. Then, the multi-level hierarchy is imposed via two geometric entailment constraints. In addition, we introduce a new Graph-aware Mamba (GaMamba) model, which incorporates topology-derived structural prompts into Mamba to capture long-range dependencies while preserving graph topological information. Experiments on ABIDE-I and REST-MDD demonstrate that HLBG outperforms state-of-the-art methods and identifies disorder-relevant functional biomarkers.
We present Supervised Deep Multimodal Matrix Factorization (SD3MF), an interpretable framework for integrative brain network analysis that generalizes Symmetric Nonnegative Matrix Tri-Factorization (SNMTF) from unsupervised single-graph clustering to supervised prediction over populations of multimodal graphs. SD3MF learns deep hierarchical factorizations for each modality together with a shared latent representation that aligns subjects across views. An encoder-decoder formulation jointly optimizes graph reconstruction and supervised prediction, while adaptive weights enable data-driven multimodal fusion. By representing each subject through community-level interaction matrices, the model yields interpretable and discriminative features. Experiments on multimodal connectome datasets show that SD3MF consistently outperforms strong deep learning baselines such as CNNs and GNNs, while enabling biologically interpretable insights. Code for reproducibility is available at: https://github.com/amjadseyedi/SD3MF.