A Dual Cross-Attention Graph Learning Framework For Multimodal MRI-Based Major Depressive Disorder Detection

Classification models based on resting-state functional magnetic resonance imaging (rs-fMRI) often show lower performance at imaging sites not included during model development, which can limit their use in clinical settings. Domain generalization (DG) addresses this issue by learning representations from source sites that remain effective for unseen target sites. However, existing DG approaches for psychiatric disorder classification commonly rely on a single imaging modality and may not fully account for site-specific acquisition effects on the learned representation space. Subjects scanned at the same site share scanner hardware, acquisition settings, and preprocessing characteristics, which can cause representations to reflect acquisition conditions rather than diagnostic information. In this work, we present M2LG-DG, a source-only multimodal local-global framework for cross-site major depressive disorder (MDD) classification. The framework employs a dual-stream rs-fMRI encoder, where the global pathway models inter-regional dependencies through self-attention and the local pathway performs graph-constrained aggregation over functional connectivity-derived brain graphs. Imaging and non-imaging representations are decomposed into shared and private components and integrated through bidirectional cross-attention with a learned modality gate. A cross-site supervised contrastive objective forms positive pairs from same-class subjects acquired at different source sites, encouraging the fused representation to preserve diagnostic information across acquisition domains. On four held-out REST-meta-MDD sites, M2LG-DG achieves an AUC of 69.48% and exceeds the closest comparison method by 2.18 percentage points. Experiments on the Autism Brain Imaging Data Exchange (ABIDE) dataset further support its applicability to other psychiatric neuroimaging classification tasks.

Cross-site identification of major depressive disorder (MDD) from resting-state functional magnetic resonance imaging (rs-fMRI) is hindered by inter-site distribution shifts and heterogeneous functional connectivity (FC) views. These views capture complementary neural relationships but exhibit distinct site biases and graph topologies, complicating alignment without sacrificing disease-relevant information or cross-view consistency. Existing studies largely treat multi-view connectome learning and cross-site adaptation separately. To the best of our knowledge, few studies have jointly modeled multiple FC views under multi-source unsupervised domain adaptation for cross-site rs-fMRI-based MDD classification. We construct Pearson correlation, sparse representation, and Granger causality graphs, each encoded by a view-specific graph attention network. Dual-stream adaptive fusion explicitly integrates pairwise cross-view interactions, followed by lightweight hyperbolic residual encoding for curvature-aware representation refinement. Class-wise Cauchy--Schwarz alignment reduces inter-source and source-target discrepancies, complemented by adversarial learning, information maximization, and confidence-aware pseudo-labeling. Across seven unlabeled target domains, our framework achieves 73.60% mean accuracy and 71.90% AUC, demonstrating effective generalization under heterogeneous acquisition conditions. These results highlight the effectiveness of unified heterogeneous-view modeling, curvature-aware refinement, and multi-source domain adaptation for cross-site MDD identification.The source code is at https://github.com/OPUS-Lightphenexx/MM-HyperGDA

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by atypical functional brain connectivity and subtle structural alterations. rs-fMRI has been widely used to identify disruptions in large-scale brain networks, while structural MRI provides complementary information about morphological organization. Despite their complementary nature, effectively integrating these heterogeneous imaging modalities within a unified framework remains challenging. This study proposes a multimodal graph learning framework that preserves the dominant role of functional connectivity while integrating structural imaging and phenotypic information for ASD classification. The proposed framework is evaluated on ABIDE-I dataset. Each subject is represented as a node within a population graph. Functional and structural features are extracted as modality-specific node attributes, while inter-subject relationships are modeled using a pairwise association encoder (PAE) based on phenotypic information. Two Edge Variational GCNs are trained to learn subject-level embeddings. To enable effective multimodal integration, we introduce a novel asymmetric transformer-based cross-attention mechanism that allows functional embeddings to selectively incorporate complementary structural information while preserving functional dominance. The fused embeddings are then passed to a MLP for ASD classification. Using stratified 10-fold cross-validation, the framework achieved an AUC of 87.3% and an accuracy of 84.4%. Under leave-one-site-out cross-validation (LOSO-CV), the model achieved an average cross-site accuracy of 82.0%, outperforming existing methods by approximately 3% under 10-fold cross-validation and 7% under LOSO-CV. The proposed framework effectively integrates heterogeneous multimodal data from the multi-site ABIDE-I dataset, improving automated ASD classification across imaging sites.