Spatio-temporal learning and explaining for dynamic functional connectivity analysis: Application to depression.

Background: Functional connectivity has been shown to fluctuate over time. The present study aimed to identifying major depressive disorders (MDD) with dynamic functional connectivity (dFC) from resting-state fMRI data, which would be helpful to produce tools of early depression diagnosis and enhance our understanding of depressive etiology.

Methods: The resting-state fMRI data of 178 subjects were collected, including 89 MDD and 89 healthy controls. We propose a spatio-temporal learning and explaining framework for dFC analysis. A yet effective spatio-temporal model is developed to classifying MDD from healthy controls with dFCs. The model is a stacking neural network model, which learns network structure information by a multi-layer perceptron based spatial encoder, and learns time-varying patterns by a Transformer based temporal encoder. We propose to explain the spatio-temporal model with a two-stage explanation method of importance feature extracting and disorder-relevant pattern exploring. The layer-wise relevance propagation (LRP) method is introduced to extract the most relevant input features in the model, and the attention mechanism with LRP is applied to extract the important time steps of dFCs. The disorder-relevant functional connections, brain regions, and brain states in the model are further explored and identified.

Results: We achieved the best classification performance in identifying MDD from healthy controls with dFC data. The top important functional connectivity, brain regions, and dynamic states closely related to MDD have been identified.

Limitations: The data preprocessing may affect the classification performance of the model, and this study needs further validation in a larger patient population.

Conclusions: The experimental results demonstrate that the proposed spatio-temporal model could effectively classify MDD, and uncover structural and temporal patterns of dFCs in depression.