Learning Structural-Functional Brain Representations through Multi-Scale Adaptive Graph Attention for Cognitive Insight

Integrating structural and functional connectomes remains challenging because their relationship is non-linear and organized over nested modular hierarchies. We propose a hierarchical multiscale structure-function coupling framework for connectome integration that jointly learns individualized modular organization and hierarchical coupling across structural connectivity (SC) and functional connectivity (FC). The framework includes: (i) Prototype-based Modular Pooling (PMPool), which learns modality-specific multiscale communities by selecting prototypical ROIs and optimizing a differentiable modularity-inspired objective; (ii) an Attention-based Hierarchical Coupling Module (AHCM) that models both within-hierarchy and cross-hierarchy SC-FC interactions to produce enriched hierarchical coupling representations; and (iii) a Coupling-guided Clustering loss (CgC-Loss) that regularizes SC and FC community assignments with coupling signals, allowing cross-modal interactions to shape community alignment across hierarchies. We evaluate the model's performance across four cohorts for predicting brain age, cognitive score, and disease classification. Our model consistently outperforms baselines and other state-of-the-art approaches across three tasks. Ablation and sensitivity analyses verify the contributions of key components. Finally, the visualizations of learned coupling reveal interpretable differences, suggesting that the framework captures biologically meaningful structure-function relationships.

Understanding how large-scale functional brain networks reorganize during cognitive decline remains a central challenge in neuroimaging. While recent self-supervised models have shown promise for learning representations from resting-state fMRI, their internal mechanisms are difficult to interpret, limiting mechanistic insight. We propose BrainInterNet, a network-aware self-supervised framework based on masked reconstruction with cross-attention that explicitly models inter-network dependencies in rs-fMRI. By selectively masking predefined functional networks and reconstructing them from remaining context, our approach enables direct quantification of network predictability and interpretable analysis of cross-network interactions. We train BrainInterNet on multi-cohort fMRI data (from the ABCD, HCP Development, HCP Young Adults, and HCP Aging datasets) and evaluate on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, in total comprising 5,582 recordings. Our method reveals systematic alterations in the brain's network interactions under AD, including in the default mode, limbic, and attention networks. In parallel, the learned representations support accurate Alzheimer's-spectrum classification and yield a compact summary marker that tracks disease severity longitudinally. Together, these results demonstrate that network-guided masked modeling with cross-attention provides an interpretable and effective framework for characterizing functional reorganization in neurodegeneration.

Structural connectivity (SC) and functional connectivity (FC) provide complementary information on interactions between brain regions and are widely used in neuroimaging studies of neuropsychiatric disorders. Generative modelling can alleviate the scarcity of large-scale paired SC-FC data, but existing approaches typically use pairwise graphs that capture only dyadic interactions and often generate SC and FC independently, limiting preservation of higher-order structure-function relationships. We propose a Multimodal Hypergraph Flow Matching (MHG-FM) framework for joint SC-FC connectivity generation and cross-modal translation. MHG-FM constructs modality-specific hypergraphs, learns higher-order representations with Hypergraph Neural Network (HGNN) encoders, and performs bidirectional cross-modal fusion using Dual Cross-Attention (DCA). A variational autoencoder maps the fused representations to a compact latent space, where conditional flow matching enables connectivity synthesis and multimodal translation via latent transport. Experiments on the Human Connectome Project Young Adult (HCP-YA) dataset show that MHG-FM outperforms several state-of-the-art baselines in reconstruction quality, topology preservation, distributional similarity, and SC-FC coupling, while achieving approximately 8x faster sampling than a matched diffusion backbone.