fMRI-Diffusion: Generating fMRI Time Series Via a Temporal Transformer Diffusion Model for Major Depressive Disorder Diagnosis
Authors: Muhammad Asif Hasan, Yanming Zhu, Xuefei Yin, Alan Wee-Chung Liew
Abstract
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.
Major depressive disorder (MDD) is a common neuropsychiatric condition whose accurate diagnosis from resting-state functional magnetic resonance imaging (rs-fMRI) remains difficult. Dynamic functional connectivity (DFC) captures time-varying interactions among brain regions and provides rich spatio-temporal information, yet current DFC-based methods face three limitations: sliding-window Pearson correlation yields noisy estimates sensitive to window length and motion artifacts; correlation-derived node features do not fully exploit frequency-domain properties of blood-oxygen-level-dependent (BOLD) signals; and most spatio-temporal graph models handle spatial structure and temporal dynamics in separate stages, restricting their ability to represent coupled brain network evolution. To overcome these issues, we reformulate DFC learning as joint spatio-temporal graph representation learning under a Hawkes-process-inspired temporal dependency prior and propose HWSTCL, a two-stage framework built on a reliability-refined joint spatio-temporal graph with a kernel-weighted pretraining objective. Within each temporal window, BOLD signals are encoded as spectral node descriptors and functional edges are refined by an exponential distance-decay prior that down-weights less reliable long-range connections. The joint graph is then formed by linking each region to itself across future windows through a Hawkes-inspired exponential kernel, allowing spatial and temporal information to be propagated together during message passing. A kernel-weighted contrastive objective further promotes temporal consistency for each region across windows while reducing redundant similarity between different regions. Experiments on a benchmark rs-fMRI dataset show that HWSTCL outperforms recent baselines and yields coherent spatio-temporal representations for MDD diagnosis.
Deep learning-based Major Depressive Disorder (MDD) detection using Electroencephalography (EEG) is fundamentally constrained by the "small-sample dilemma." Prevailing generative data augmentation methods not only incur heavy computational overhead but also risk introducing synthetic noise, thereby blurring classification boundaries. To challenge the traditional "data quantity first" convention, we propose a novel framework "Beyond Augmentation": Score-Guided Classification (SGC). SGC does not synthesize pseudo-samples; instead, it utilizes an unsupervised generative network architecture to model the structural and statistical anomaly degrees of samples, serving as the core "Pathological Prior". This prior, after robust normalization, is explicitly fused with deep feature representations, thereby precisely guiding the classifier's decision boundary. Furthermore, to dynamically adapt to varying channel configurations, we propose a Cross-Channel Spatial Adaptation module, utilizing a spatial mapping mechanism to effectively resolve the hardware heterogeneity of mismatched channels in multi-center datasets. Extensive experiments on the Mumtaz2016 and high-density MODMA datasets demonstrate the effectiveness and exceptional generalizability of our method under the challenging "zero data augmentation" setting and at "zero sample synthesis cost". Keywords: Electroencephalography (EEG), Depression Detection, Anomaly Score, Diffusion Models, Few-Shot Learning
Cross-site identification of major depressive disorder (MDD) from resting-state functional magnetic resonance imaging (rs-fMRI) is hindered by inter-site distribution shifts and heterogeneous functional connectivity (FC) views. These views capture complementary neural relationships but exhibit distinct site biases and graph topologies, complicating alignment without sacrificing disease-relevant information or cross-view consistency. Existing studies largely treat multi-view connectome learning and cross-site adaptation separately. To the best of our knowledge, few studies have jointly modeled multiple FC views under multi-source unsupervised domain adaptation for cross-site rs-fMRI-based MDD classification. We construct Pearson correlation, sparse representation, and Granger causality graphs, each encoded by a view-specific graph attention network. Dual-stream adaptive fusion explicitly integrates pairwise cross-view interactions, followed by lightweight hyperbolic residual encoding for curvature-aware representation refinement. Class-wise Cauchy--Schwarz alignment reduces inter-source and source-target discrepancies, complemented by adversarial learning, information maximization, and confidence-aware pseudo-labeling. Across seven unlabeled target domains, our framework achieves 73.60% mean accuracy and 71.90% AUC, demonstrating effective generalization under heterogeneous acquisition conditions. These results highlight the effectiveness of unified heterogeneous-view modeling, curvature-aware refinement, and multi-source domain adaptation for cross-site MDD identification.The source code is at https://github.com/OPUS-Lightphenexx/MM-HyperGDA