Altered Functional Specialization and Interhemispheric Coordination in Rhegmatogenous Retinal Detachment: Associations With Gene Expression, Neurotransmitter Receptor Distribution, and SVM-SHAP Classification: A Multimodal Neuroimaging-Transcriptomics Study Integrating Functional Metrics and Interpretable Machine Learning.

BACKGROUND: Previous studies have reported functional alterations in the brains of patients with rhegmatogenous retinal detachment (RRD). However, it remains largely unclear whether RRD affects hemispheric specialization and interhemispheric coordination, and how these alterations relate to underlying gene expression patterns and neurotransmitter receptor distributions. METHODS: We employed the Autonomy Index (AI) and Connectivity between Functionally Homotopic Voxels (CFH) to quantify alterations in hemispheric specialization and interhemispheric cooperation in patients with RRD. Transcriptome-neuroimaging spatial correlation analysis was performed by integrating gene expression data from the Allen Human Brain Atlas (AHBA) to identify genes associated with AI and CFH alterations. Enrichment and protein-protein interaction analyses were conducted to characterize the biological processes and molecular features of these genes. Furthermore, we explored the spatial associations between AI/CFH abnormalities and neurotransmitter receptor distributions. Finally, a support vector machine (SVM) classifier combined with Shapley additive explanations (SHAP) was implemented to distinguish RRD patients from healthy controls (HCs) and to determine the most discriminative brain regions. RESULTS: RRD patients exhibited significant alterations in AI and CFH within the frontal lobe, occipital lobe, and thalamus. Transcriptome-neuroimaging integration revealed gene sets closely associated with these abnormalities. These genes were primarily enriched in key biological processes including synaptic signaling, sensory organ development, Notch signaling, and structural neuroplasticity. The spatial pattern of CFH changes showed strong alignment with the regional distributions of multiple neurotransmitter systems, particularly serotonergic, dopaminergic, glutamatergic, and cholinergic pathways. Finally, the SVM-SHAP classification framework identified CFH in the right thalamus as the most discriminative feature for differentiating RRD patients from HCs. CONCLUSION: These findings deepen our neurobiological understanding of RRD-induced brain functional remodeling and provide theoretical support and a methodological foundation for developing central intervention strategies and potential discriminative imaging tools for retinal diseases.