BDHT: Generative AI Enables Causality Analysis for Mild Cognitive Impairment

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 connectivity 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 diffuser is the first generative model to apply diffusion models to the application of generating and analyzing multimodal brain networks. Specifically, the BDHT leverages 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. By stacking the multi-head attention and graph convolutional network, the graph convolutional transformer (GraphConformer) module is devised to enhance structure-function complementarity and improve the ability in noise estimation. Experimental evaluations of the denoising diffusion model demonstrate its effectiveness in estimating effective connectivity. The proposed model achieves superior performance in terms of accuracy and robustness compared to existing approaches. Moreover, the proposed model can identify altered directional connections and provide a comprehensive understanding of parthenogenesis for MCI treatment. Note to Practitioners—Diagnosing MCI allows for timely intervention and treatment measures to potentially slow down or even halt further cognitive decline. Exploring causal relations between brain regions enables a better understanding of pathogenic mechanisms and the development of effective biomarkers for MCI diagnosis. The current practice heavily relies on the software to analyze MCI causality, leading to large computing errors and degrading MCI analysis performance because of different parameter settings. This work aims to provide a unified framework for the estimation of brain effective connectivity using generative artificial intelligence. Due to their ability to generate high-quality samples, diffusion models have demonstrated remarkable performance in cross-modal medical image synthesis through iterative denoising processes. Our model provides a new insight into how to transform four-dimensional functional magnetic resonance imaging into effective connectivity without relying on software toolkits. The proposed model achieves good disease prediction performance and identifies altered directional connections that may be potential biomarkers for MCI treatment. Our work enables practitioners to develop deep learning model-based medical tools to assist clinicians with disease diagnosis and pathological analysis in an efficient way. Our work can also extend to the intelligently assisted diagnosis of other neurological diseases.