Beyond Phenotypic Similarity: Relation Refinement and Selective Population Graph Learning for Multimodal Brain Disorder Diagnosis

Mental disorder populations exhibit pronounced heterogeneity -- that is, the significant differences between samples -- poses a significant challenge to the definition of positive pairs in contrastive learning. To address this, we propose a subtype-guided contrastive learning framework that models patient heterogeneity as latent subtypes and incorporates them as structural priors to guide discriminative representation learning. Specifically, we construct multi-view representations by combining patients' clinical text with graph structure adaptively learned from BOLD signals, to uncover latent subtypes via unsupervised spectral clustering. A dual-level attention mechanism is proposed to construct prototypes for capturing stable subtype-specific connectivity patterns. We further propose a subtype-guided contrastive learning strategy that pulls samples toward their subtype prototype graph, reinforcing intra-subtype consistency for providing effective supervisory signals to improve model performance. We evaluate our method on Major Depressive Disorder (MDD), Bipolar Disorder (BD), and Autism Spectrum Disorders (ASD). Experimental results confirm the effectiveness of subtype prototype graphs in guiding contrastive learning and demonstrate that the proposed approach outperforms state-of-the-art approaches. Our code is available at https://anonymous.4open.science/r/BrainSCL-06D7.

Brain imaging classification is commonly approached from two perspectives: modeling the full image volume to capture global anatomical context, or constructing ROI-based graphs to encode localized and topological interactions. Although both representations have demonstrated independent efficacy, their relative contributions and potential complementarity remain insufficiently understood. Existing fusion approaches are typically task-specific and do not enable controlled evaluation of each representation under consistent training settings. To address this gap, we propose a unified cross-view contrastive framework for joint imaging-ROI representation learning. Our method learns subject-level global (imaging) and local (ROI-graph) embeddings and aligns them in a shared latent space using a bidirectional contrastive objective, encouraging representations from the same subject to converge while separating those from different subjects. This alignment produces comparable embeddings suitable for downstream fusion and enables systematic evaluation of imaging-only, ROI-only, and joint configurations within a unified training protocol. Extensive experiments on the ADHD-200 and ABIDE datasets demonstrate that joint learning consistently improves classification performance over either branch alone across multiple backbone choices. Moreover, interpretability analyses reveal that imaging-based and ROI-based branches emphasize distinct yet complementary discriminative patterns, explaining the observed performance gains. These findings provide principled evidence that explicitly integrating global volumetric and ROI-level representations is a promising direction for neuroimaging-based brain disorder classification. The source code is available at https://anonymous.4open.science/r/imaging-roi-contrastive-152C/.

Modeling the complex interactions among functional subnetworks is crucial for the diagnosis of mental disorders and the identification of functional pathways. However, learning the interactions of the underlying subnetworks remains a significant challenge for existing Transformer-based methods due to the limited number of training samples. To address these challenges, we propose KD-Brain, a Prior-Informed Graph Learning framework for explicitly encoding prior knowledge to guide the learning process. Specifically, we design a Semantic-Conditioned Interaction mechanism that injects semantic priors into the attention query, explicitly navigating the subnetwork interactions based on their functional identities. Furthermore, we introduce a Pathology-Consistent Constraint, which regularizes the model optimization by aligning the learned interaction distributions with clinical priors. Additionally, KD-Brain leads to state-of-the-art performance on a wide range of disorder diagnosis tasks and identifies interpretable biomarkers consistent with psychiatric pathophysiology. Our code is available at https://anonymous.4open.science/r/KDBrain.