Effective connectivity estimation plays a crucial role in understanding the interactions and information flow between different brain regions. However, the functional time series used for estimating effective connentivity is derived from certain software, which may lead to large computing errors because of different parameter settings and degrade the ability to model complex causal relationships between brain regions. In this paper, a brain diffuser with hierarchical transformer (BDHT) is proposed to estimate effective connectivity for mild cognitive impairment (MCI) analysis. To our best knowledge, the proposed brain diffuer is the first generative model to apply diffusion models in the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages the structural connectivity to guide the reverse processes in an efficient way. It makes the denoising process more reliable and guarantees effective connectivity estimation accuracy. To improve denoising quality, the hierarchical denoising transformer is designed to learn multi-scale features in topological space. Furthermore, the GraphConFormer block can concentrate on both global and adjacent connectivity information. By stacking the multi-head attention and graph convolutional network, the proposed model enhances structure-function complementarity and improves the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The method achieves superior performance in terms of accuracy and robustness compared to existing approaches. It can captures both unidirectal and bidirectional interactions between brain regions, providing a comprehensive understanding of the brain's information processing mechanisms.

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