VarCoNet: A variability-aware self-supervised framework for functional connectome extraction from resting-state fMRI

Accounting for inter-individual variability in brain function is key to precision medicine. Here, by considering functional inter-individual variability as meaningful data rather than noise, we introduce VarCoNet, an enhanced self-supervised framework for robust functional connectome (FC) extraction from resting-state fMRI (rs-fMRI) data. VarCoNet employs self-supervised contrastive learning to exploit inherent functional inter-individual variability, serving as a brain function encoder that generates FC embeddings readily applicable to downstream tasks even in the absence of labeled data. Contrastive learning is facilitated by a novel augmentation strategy based on segmenting rs-fMRI signals. At its core, VarCoNet integrates a 1D-CNN-Transformer encoder for advanced time-series processing, enhanced with a robust Bayesian hyperparameter optimization. Our VarCoNet framework is evaluated on two downstream tasks: (i) subject fingerprinting, using rs-fMRI data from the Human Connectome Project, and (ii) autism spectrum disorder (ASD) classification, using rs-fMRI data from the ABIDE I and ABIDE II datasets. Using different brain parcellations, our extensive testing against state-of-the-art methods, including 13 deep learning methods, demonstrates VarCoNet's superiority, robustness, interpretability, and generalizability. Overall, VarCoNet provides a versatile and robust framework for FC analysis in rs-fMRI.