Network-Aware Bilinear Tokenization for Brain Functional Connectivity Representation Learning
Authors: Leo Milecki, Qingyu Hu, Bahram Jafrasteh, Mert R. Sabuncu, Qingyu Zhao
Organizations: Department of Radiology, Weill Cornell Medicine, New York, NY, USA. · School of Electrical and Computer Engineering, Cornell University and Cornell Tech, New York, NY, USA.
Abstract
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.
Brain networks exhibit a modular community structure that varies across individuals and neurological conditions. However, existing self-supervised learning (SSL) methods often overlook this heterogeneity, relying on generic masking strategies that fail to capture subject-specific functional organization. We propose BrainPICM, a self-supervised framework for brain network analysis via progressive individualized community aware masking. BrainPICM formulates ROI-to-community mapping as a progressive unbalanced optimal transport process, yielding soft assignments and per-ROI confidence scores. Guided by these confidence estimates, a curriculum-style masking strategy gradually incorporates low-confidence, potentially pathological regions into training, enabling the model to learn both stable modular structures and individual variations. Additionally, a deviation-aware aggregation module quantifies functional reorganization by measuring mass redistribution relative to a population template, enhancing interpretability and downstream prediction. Experiments on three fMRI datasets (ABIDE-I, ADHD-200, ADNI) show that BrainPICM consistently outperforms state-of-the-art supervised and SSL methods in diagnostic accuracy, indicating that explicitly injecting modular community structure into masked modeling yields more functionally consistent and generalizable representations. The source code for this approach will be released at https://github.com/Hrychen7/BrainPICM.
Functional connectivity (FC) derived from resting-state fMRI is widely used to characterize large-scale brain network alterations in neurological and psychiatric disorders. However, FC construction critically depends on the choice of brain atlas, and different parcellations may emphasize distinct organizational features, leading to heterogeneous and sometimes inconsistent representations. Existing multi-atlas approaches partially alleviate this issue but often fuse atlas-derived features or predictions at a relatively shallow level, while single-atlas disentanglement methods do not explicitly address cross-atlas heterogeneity. We propose Multi-Atlas Disentangled Connectivity LEarning (MADCLE), a multi-branch representation learning framework that jointly encodes FC matrices derived from different brain atlases. Rather than introducing a single explicitly shared latent variable across parcellations, MADCLE learns atlas-wise disease-related representations and encourages them to be cross-atlas consistent through distributional alignment. Meanwhile, covariate-related and atlas-dependent residual factors are modeled separately using covariate similarity supervision, atlas-specific reconstruction, and decorrelation constraints, thereby reducing the leakage of non-disease and parcellation-dependent information into the disease-related embeddings. Experiments on the ADNI and ADHD-200 datasets suggest that MADCLE achieves competitive or improved performance compared with single-atlas baselines, multi-atlas GNN/Transformer models, and recent multi-atlas consistency frameworks. These results support the potential value of structured disentanglement for FC-based disorder identification under heterogeneous parcellation schemes.
Self-supervised pretraining is promising for large-scale neuroimaging, yet the impact of region-aware masking and hybrid sequence modeling remains underexplored. In this work, we introduce Rhamba, a region-aware pretraining framework that integrates anatomically guided masking with hybrid Attention-Mamba architectures for resting state functional magnetic resonance imaging (fMRI) analysis. Models were pretrained on the ABIDE dataset using region-aligned patch embeddings and three masking strategies (Any, Majority, and Pure) with increasing spatial specificity. We evaluated four architectural variants: a Mamba only model, an Alternate architecture with interleaved Mamba and Attention blocks, and two hybrid encoder-decoder configurations (Attention-Mamba (AM) and Mamba-Attention (MA)). The pretrained models were fine-tuned on downstream classification tasks using the COBRE and ADHD-200 datasets for schizophrenia and attention-deficit/hyperactivity disorder discrimination. We employed Integrated Gradients, an explainable AI method, to identify the brain regions contributing to model predictions. Masking strategy strongly influenced reconstruction behavior, with reconstruction loss following a consistent ordering (Any > Majority > Pure). However, this trend did not directly translate into downstream performance, where differences were modest and dataset-dependent. The hybrid architecture with the MA configuration achieved the highest average AUROC across both datasets, and Rhamba outperformed state-of-the-art methods in comparative evaluation. Region-wise analysis showed that peak performance depends on the interaction between masking strategy and architecture rather than a single dominant configuration. Overall, Rhamba offers a flexible framework for balancing interpretability, scalability, and performance in large-scale fMRI representation learning.