The objective of this study was to investigate underlying mechanisms of long-term effective weight loss after laparoscopic sleeve gastrectomy (LSG) and effects on the medial orbitofrontal cortex (mOFC) and cognition. A total of 18 individuals with obesity (BMI ≥ 30 kg/m2) underwent LSG. Clinical data, cognitive scores, and brain magnetic resonance imaging scans were evaluated before LSG and 12 months after LSG. We employed voxel-based morphometry analysis and seed-based resting-state functional connectivity (RSFC) analysis to assess LSG-induced structural and functional changes in mOFC. Partial correlation analysis and univariate and multivariate linear regression models were used to explore associations among biochemical indexes, neuroimaging, cognition, and weight loss. No significant improvement in general cognition was found after LSG. Decreases in gray matter volume of the bilateral mOFC and increases in RSFC of the right mOFC were observed 12 months after LSG. Weight loss was associated with RSFC, general cognitive scores, and triglyceride changes. Multivariate linear regression model revealed gray matter volume of the left mOFC and working memory scores at baseline explained 55.2% of the variation in weight loss. These findings suggest that mOFC imaging and cognitive scores could serve as biomarkers for predicting persistent weight loss after LSG, which provides a solid foundation for a potential target for neuromodulation research.
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