Multi-resolution Spatiotemporal Enhanced Transformer Denoising with Functional Diffusive GANs for Constructing Brain Effective Connectivity in MCI analysis

Effective connectivity can describe the causal patterns among brain regions. These patterns have the potential to reveal the pathological mechanism and promote early diagnosis and effective drug development for cognitive disease. However, the current studies mainly focus on using empirical functional time series to calculate effective connections, which may not comprehensively capture the complex causal relationships between brain regions. In this paper, a novel Multi-resolution Spatiotemporal Enhanced Transformer Denoising (MSETD) network with an adversarially functional diffusion model is proposed to map functional magnetic resonance imaging (fMRI) into effective connectivity for mild cognitive impairment (MCI) analysis. To be specific, the denoising framework leverages a conditional diffusion process that progressively translates the noise and conditioning fMRI to effective connectivity in an end-to-end manner. To ensure reverse diffusion quality and diversity, the multi-resolution enhanced transformer generator is designed to extract local and global spatiotemporal features. Furthermore, a multi-scale diffusive transformer discriminator is devised to capture the temporal patterns at different scales for generation stability. Evaluations of the ADNI datasets demonstrate the feasibility and efficacy of the proposed model. The proposed model not only achieves superior prediction performance compared with other competing methods but also identifies MCI-related causal connections that are consistent with clinical studies.