Rhamba: Region-Aware Hybrid Attention-Mamba Framework for Self-Supervised Learning in Resting-State fMRI

Functional magnetic resonance imaging (fMRI) is a powerful tool for investigating human brain function. However, the high cost of data acquisition and the inherent subjectivity of psychiatric rating scales often lead to datasets with small sample sizes and variable label quality, especially when targeting a specific neurological condition. Combined with the inherently high dimensionality of fMRI data, these limitations substantially increase the risk of model overfitting. Recent years have seen growing interest in developing fMRI foundation models by combining multiple datasets; however, the computational resources needed for pretraining and fine-tuning are often prohibitive. We show that a lightweight self-supervised framework yields representations that generalize across diverse downstream tasks, outperforming fully supervised baselines and approaching the performance of large-scale models. We introduce BrainSimSiam, a data-efficient self-supervised representation learning framework that leverages positive-only data pairs to learn robust and generalizable features. We demonstrate that the learned representations achieve strong performance across multiple downstream classification and regression tasks, highlighting the potential of BrainSimSiam for data-limited neuroimaging applications.

Accurate identification of Alzheimers disease (AD) using resting-state functional magnetic resonance imaging (rs-fMRI) remains challenging due to the high dimensionality, noise, and complex inter-regional dependencies inherent in functional brain connectivity, which limit the effectiveness of traditional approaches based on handcrafted connectivity features or conventional machine learning models. In this work, we present an attention-based deep learning framework for Alzheimers disease classification that operates directly on rs-fMRI functional connectivity matrices by treating brain regions as tokens and employing a Transformer-inspired self-attention mechanism to model long-range and global functional dependencies across distributed brain networks. The proposed framework learns discriminative functional representations without reliance on manual feature engineering and is evaluated on a longitudinal cohort from the Alzheimers Disease Neuroimaging Initiative (ADNI) comprising cognitively normal and Alzheimers disease subjects with multiple visits. A subject-wise evaluation protocol is adopted to prevent information leakage across visits, and class-weighted optimization is incorporated to address mild class imbalance. Experimental results for binary AD versus cognitively normal classification demonstrate that the proposed attention- based rs-fMRI model achieves an accuracy of 88.95% and a ROC-AUC of 0.90, along with a favorable precision-recall balance, highlighting the effectiveness of self-attention-driven functional connectivity modeling as a robust and interpretable approach for Alzheimers disease detection using resting-state fMRI.

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.