Explaining deep learning-based representations of resting state functional connectivity data: focusing on interpreting nonlinear patterns in autism spectrum disorder.

Background: Resting state Functional Magnetic Resonance Imaging fMRI (rs-fMRI) has been used extensively to study brain function in psychiatric disorders, yielding insights into brain organization. However, the high dimensionality of the rs-fMRI data presents significant challenges for data analysis. Variational autoencoders (VAEs), a type of neural network, have been instrumental in extracting low-dimensional latent representations of resting state functional connectivity (rsFC) patterns, thereby addressing the complex nonlinear structure of rs-fMRI data. Despite these advances, interpreting these latent representations remains a challenge. This paper aims to address this gap by developing explainable VAE models and testing their utility using rs-fMRI data in autism spectrum disorder (ASD). Methods: One-thousand one hundred and fifty participants (601 healthy controls [HC] and 549 patients with ASD) were included in the analysis. RsFC correlation matrices were extracted from the preprocessed rs-fMRI data using the Power atlas, which includes 264 regions of interest (ROIs). Then VAEs were trained in an unsupervised manner. Lastly, we introduce our latent contribution scores to explain the relationship between estimated representations and the original rs-fMRI brain measures. Results: We quantified the latent contribution scores for both the ASD and HC groups at the network level. We found that both ASD and HC groups share the top network connectivitives contributing to all estimated latent components. For example, latent 0 was driven by rsFC within ventral attention network (VAN) in both the ASD and HC. However, we found significant differences in the latent contribution scores between the ASD and HC groups within the VAN for latent 0 and the sensory/somatomotor network for latent 2. Conclusion: This study introduced latent contribution scores to interpret nonlinear patterns identified by VAEs. These scores effectively capture changes in each observed rsFC feature as the estimated latent representation changes, enabling an explainable deep learning model that better understands the underlying neural mechanisms of ASD.