A causal bidirectional selective state space model for imaging genetics in neurodegenerative diseases

Brain imaging genetics aims to uncover the pathological mechanisms and improve the diagnosis of brain diseases, particularly neurodegenerative disorders. While deep learning has advanced feature extraction and association modeling in this field, there are still two major challenges: extracting meaningful information from long genetic sequences and establishing causal relationships among genetics, imaging, and disease. To address these challenges, this paper proposes a deep causal bidirectional selective state space model (CausalMamba) that integrates multi-level feature extraction and causal inference into a unified representation learning framework. First, the long-sequence genetic data and whole-brain imaging data are divided into localized parts, extracting the fine-grained features. Then, a causal inference strategy based on counterfactual reasoning and contrastive learning is proposed to identify the most relevant genetic and imaging features and to construct a causal chain from genetics to disease via imaging. Finally, a bidirectional selective state space model (BiMamba) efficiently integrates the selected features into modality-specific global features, enabling accurate disease diagnosis. Our model is trained jointly on genetic and imaging data, but requires only genetic data at test time. We validate the proposed method on the simulated dataset, Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and Parkinson's Progression Markers Initiative (PPMI) dataset. Experimental results show that our method achieves accuracies of 80.5% and 77.3% using only genetic data in classifying Alzheimer's and Parkinson's diseases from normal controls, respectively, with the relative improvements of 4.2% and 2.7% over the state-of-the-art methods while also being more computationally efficient. The results demonstrate that CausalMamba can effectively identify causally relevant biomarkers across the entire genome and brain.