<p>Convergent evidence has suggested that the disruption of either structural connectivity (SC) or functional connectivity (FC) in the brain can lead to various neuropsychiatric disorders. Since changes in SC-FC coupling may be more sensitive than a single modality to detect subtle brain connectivity abnormalities, a few learning-based methods have been proposed to explore the relationship between SC and FC. However, these existing methods still fail to explain the relationship between altered SC-FC coupling and brain disorders. Therefore, in this paper, we explore three types of tree-based ensemble models (i.e., Decision Tree, Random Forest, and Adaptive Boosting) toward counterfactual explanations for SC-FC coupling. Specifically, we first construct SC and FC matrices from preprocessed diffusion-weighted DTI and resting-state functional fMRI data. Then, we quantify the SC-FC coupling strength of each region and convert it into feature vectors. Subsequently, we select SC-FC coupling features that can reflect disease-related information and trained three tree-based models to analyze the predictive role of these coupling features for diseases. Finally, we design a tree ensemble counterfactual explanation model to generate a set of counterfactual examples for patients, thereby assisting the diagnosis of brain diseases by fine-tuning the patient’s abnormal SC-FC coupling feature vector. Experimental results on two independent datasets (i.e., epilepsy and schizophrenia) validate the effectiveness of the proposed method. The identified discriminative brain regions and generated counterfactual examples provide new insights for brain disease analysis.</p>