Beyond Anatomy: Explainable ASD Classification from rs-fMRI via Functional Parcellation and Graph Attention Networks

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.

Functional magnetic resonance imaging (fMRI) is a widely used technique for studying the brain. Recent methods that utilize graph neural networks (GNNs) for analysis of brain functional connectivity have shown great potential for the classification of brain disorders, such as Alzheimer's disease (AD). However, these methods often assume a preset number of functional modules across all subjects, which overlooks inter-subject variability. In addition, the discovered modules are rarely used to directly guide the learned connectivity patterns. Here, to address these issues, we propose a Meta Probabilistic Pooling GNN (MPP-GNN). We frame the model's task as a coupled, bilevel optimization that performs adaptive graph partitioning hierarchically to discover subject-specific modules and then uses the discovered brain modules as an explicit prior to guide edge refinement and representation learning. We validate MPP-GNN on two public datasets for AD classification, achieving the highest AUC in comparison to established baselines for both datasets. Furthermore, our analysis demonstrates that MPP-GNN shows significant alignment with the canonical functional-network organization defined by the Yeo brain atlas and reveals a network-level dedifferentiation pattern for AD.

Brain parcellation and classification are typically evaluated in isolation, yet downstream AD detection performance depends on their interaction. We decouple these components and systematically benchmark fast deep learning parcellation methods (SynthSeg+, OpenMAP-T1) against the FreeSurfer (FS-HV) clinical baseline through down- stream AD classification on OASIS-1. Our factorial design evaluates three parcellation methods, two volumetry strategies (hard vs. soft), and four classifier paradigms (clinical thresholds, supervised feedforward networks, ensemble methods, and foundation models with zero/few-shot prompting), with all results quantified using BCa Bootstrap 95% confidence intervals.