Exploring Subnetwork Interactions in Heterogeneous Brain Network via Prior-Informed Graph Learning

Brain network analysis based on functional Magnetic Resonance Imaging (fMRI) is pivotal for diagnosing brain disorders. Existing approaches typically rely on predefined functional sub-networks to construct sub-network associations. However, we identified many cross-network interaction patterns with high Pearson correlations that this strict, prior-based organization fails to capture. To overcome this limitation, we propose the Brain Hierarchical Organization Learning (BrainHO) to learn inherently hierarchical brain network dependencies based on their intrinsic features rather than predefined sub-network labels. Specifically, we design a hierarchical attention mechanism that allows the model to aggregate nodes into a hierarchical organization, effectively capturing intricate connectivity patterns at the subgraph level. To ensure diverse, complementary, and stable organizations, we incorporate an orthogonality constraint loss, alongside a hierarchical consistency constraint strategy, to refine node-level features using high-level graph semantics. Extensive experiments on the publicly available ABIDE and REST-meta-MDD datasets demonstrate that BrainHO not only achieves state-of-the-art classification performance but also uncovers interpretable, clinically significant biomarkers by precisely localizing disease-related sub-networks.

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.

Functional connectome analysis examines brain-region interactions to understand and identify disorders such as autism spectrum disorder and Alzheimer's disease. Existing methods typically use GNNs and Transformers to model the full functional connectivity matrix. However, processing tens of thousands of connections introduces redundancy and noise, increases computational cost, and limits connection-level interpretability. This raises a central question: do we really need complex interaction modeling, or is identifying a small set of disease-relevant connectivity patterns sufficient? To answer this question, we propose BrainLinear, a lightweight geometry-aware framework for mining disease-discriminative connectome patterns. BrainLinear first maps each functional connectivity matrix to a shared tangent space centered at the Fréchet mean of the training set, capturing subject-specific deviations while respecting matrix geometry. It then scores each ROI-pair tangent direction by its classification contribution and disease--control difference, retaining Top-$K$ directions as a compact representation. Finally, a shallow multilayer perceptron performs classification on the selected representation. Experiments on ABIDE and ADNI show that BrainLinear matches or exceeds strong GNN and Transformer baselines at a fraction of their cost: it improves AUC and ACC over the best baseline for each metric by up to $3.54$ and $1.39$ percentage points, while reducing runtime and peak GPU memory by $84.0\%$ and $68.4\%$ relative to the closest baseline in AUC. The selected directions are directionally consistent with between-group displacements and organized across major functional systems, supporting connection-level interpretation.