Continual Learning for fMRI-Based Brain Disorder Diagnosis via Functional Connectivity Matrices Generative Replay

Diagnosing Major Depressive Disorder (MDD) from functional magnetic resonance imaging (fMRI) using functional connectivity (FC) analysis requires large amounts of labeled data that are scarce in clinical settings. Existing augmentation methods synthesize FC matrices, which compress fMRI recordings into static pairwise summaries and discard temporal information. We propose fMRI-Diffusion, a framework that synthesizes region-of-interest (ROI)-level fMRI time series rather than FC matrices. A Temporal Transformer serves as the denoising network within a denoising diffusion probabilistic model, treating each time point as a token to capture temporal dependencies through self-attention. A supervised pretraining strategy initializes the Transformer with task-relevant representations before diffusion training, and FC matrices are derived from the synthesized time series for classification. Experiments on the REST-meta-MDD dataset show that augmenting training data with synthetic time series consistently improves diagnostic accuracy across ten classifiers, six parcellation atlases, and three acquisition sites. The method outperforms five recent FC-based synthesis approaches, with accuracy gains of up to 3.7 percentage points over the strongest baseline. Ablation studies confirm the contributions of both the Transformer-based denoiser and the pretraining strategy. Distributional fidelity metrics remain below 0.06 across all conditions, indicating close agreement between real and synthetic distributions. These findings suggest that synthesizing fMRI time series before FC computation preserves temporal information lost in matrix-level augmentation and provides a practical strategy for MDD diagnosis under limited data.

Resting-state fMRI (rs-fMRI) is a vital non-invasive tool for diagnosing brain disorders and uncovering pathological mechanisms. However, existing graph contrastive learning (GCL) methods often underexploit augmentation histories across training epochs and the relationships among different augmented views. In this paper, we introduce a topology-guided Multi-view graph Contrastive learning framework with Dynamic graph topology Augmentation (MCDA) for fMRI analysis. Unlike traditional GCL that uses fixed noise or edge-dropping, MCDA employs a Dynamic Augmentation Update (DAU) module that iteratively refines the augmented topology. Specifically, we incorporate self-aware and cross-sample augmentation strategies to simultaneously capture individual-specific functional signatures and inter-subject heterogeneity. We then design a topology-guided multi-view graph contrastive learning scheme that explores interrelationships not only between the original network and its augmented views, but also across different augmented views to maximize structural information preservation. We characterize the score-level optimization directions and establish a lower bound for the contrastive objective. The framework combines classification and contrastive losses for brain disorder diagnosis and examines discriminative functional connectivity patterns as potential biomarkers. Experiments on two public rs-fMRI datasets comprising 1,236 subjects demonstrate that MCDA outperforms the state-of-the-art methods. The code has been made publicly available at: https://github.com/goodcodingagoodboy/MCDA.

Functional magnetic resonance imaging (fMRI) commonly characterizes large-scale brain organization through functional connectivity (FC). However, an observed FC matrix is not a fixed brain graph but a statistical estimate determined by the finite BOLD frames used to compute it. Conventional FC-based approaches typically represent each scan with a single Pearson-correlation matrix, leaving frame-resolved variations in regional interactions unexploited. To address this limitation, we introduce CoFlu-Brain, which organizes framewise cofluctuation observations into multiple retained and dropped views, each summarized as an FC matrix. The model learns connectivity structure reproducible across retained views and predicts the representations of the corresponding dropped views, while adopting SIGReg from LeJEPA to prevent representation collapse. We pretrained CoFlu-Brain on 13,444 subjects from eight dataset groups and evaluated its representations via frozen-encoder linear probing on seven classification and two age-prediction tasks across seven datasets. CoFlu-Brain showed strong transfer across demographic, developmental, and clinical prediction tasks, outperforming the evaluated released models on most tasks. Random frame partitioning improved aggregate transfer, while the complete objective achieved the strongest overall performance. Code is available.