Progressive Self-Supervised Learning with Individualized Community Assignment for Brain Network Analysis

Masked autoencoders (MAEs) have recently shown promise for self-supervised representation learning of resting-state brain functional connectivity (FC). However, a fundamental question remains unresolved: how should FC matrices be tokenized to align with the intrinsic modular organization of large-scale brain networks? Existing approaches typically adopt region-centric or graph-based schemes that treat FC as structurally homogeneous elements and overlook the large-scale network brain organization. We introduce NERVE (Network-Aware Representations of Brain Functional Connectivity via Bilinear Tokenization), a self-supervised learning framework that redefines FC tokenization by partitioning FC matrices into patches of intra- and inter-network connectivity blocks. Unlike image-based MAE, where fixed-size patches share a common tokenizer, FC patches defined by network pairs are heterogeneous in size and correspond to distinct functional roles. To resolve this problem, NERVE embeds FC patches through a novel structured bilinear factorization. This formulation preserves network identity and reduces parameter complexity from quadratic to linear scaling in the number of networks. We evaluate NERVE across three large-scale developmental cohorts (ABCD, PNC, and CCNP) for behavior and psychopathology prediction. Compared to structurally agnostic MAE variants and graph-based self-supervised baselines, the proposed network-aware formulation yields more stable and transferable representations, particularly in cross-cohort evaluation. Ablation studies confirm that the proposed bilinear network embedding and anatomically grounded parcellation are critical for performance. These findings highlight the importance of incorporating domain-specific structural priors into self-supervised learning for functional connectomics. Code is available at: https://github.com/leomlck/NERVE.

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.

Foundation models pretrained using self-supervised learning have transformed computer vision by learning transferable representations from large-scale unlabeled data. However, existing foundation models for neuroimaging remain limited by task-specific training, slice-based learning strategies, or relatively small pretraining datasets, restricting their generalizability across diverse brain MRI applications. In this work, we present BrainNext, a general-purpose self-supervised foundation model for volumetric brain MRI analysis. BrainNext combines masked autoencoder (MAE) pretraining with a native three-dimensional Bi-Directional xLSTM-UNet architecture to learn rich anatomical representations from 60,551 unlabeled brain MRI examinations spanning multiple MRI modalities. The pretrained model is subsequently adapted to downstream tasks through lightweight task-specific fine-tuning. We evaluate BrainNext on the Foundation Models for Medical Imaging (FOMO) 2025 Method Track, encompassing classification, segmentation, and brain-age estimation, where it achieved second place overall and ranked first in the meningioma segmentation task on the official FOMO 2025 challenge leaderboard, demonstrating strong transferability across heterogeneous neuroimaging tasks. These results highlight the potential of large-scale self-supervised pretraining to learn robust and transferable volumetric representations, establishing BrainNext as a scalable foundation model for diverse brain MRI applications.