Habenula Volume and Functional Connectivity Changes Following Laparoscopic Sleeve Gastrectomy for Obesity Treatment

Background Neuroimaging studies have revealed alterations in habenular (Hb) structure and functional connectivity (FC) in psychiatric conditions. The Hb plays a particularly critical role in regulating negative emotions, which trigger excessive food intake and obesity. However, obesity and weight loss intervention (i.e., laparoscopic sleeve gastrectomy [LSG])–associated changes in Hb structure and FC have not been studied. Methods We used voxel-based morphometry analysis to measure changes in gray matter volume (GMV) in the Hb in 56 patients with obesity at pre-LSG and 12 months post-LSG and in 78 normal-weight (NW) control participants. Then, we conducted Hb seed-based resting-state FC (RSFC) to examine obesity-related and LSG-induced alterations in RSFC. Finally, we used mediation analysis to characterize the interrelationships among Hb GMV, RSFC, and behaviors. Results Compared with NW participants, Hb GMV was smaller in patients at pre-LSG and increased at 12 months post-LSG to levels equivalent to that of NW; in addition, increases in Hb GMV were correlated with reduced body mass index (BMI). Compared with NW participants, pre-LSG patients showed greater RSFCs of the Hb–insula, Hb–precentral gyrus, and Hb–rolandic operculum and weaker RSFCs of the Hb–thalamus, Hb–hypothalamus, and Hb–caudate; LSG normalized these RSFCs. Decreased RSFC of the Hb-insula was correlated with reduced BMI, Yale Food Addiction Scale rating, and emotional eating; reduced hunger levels were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus; and reduced BMI and Yale Food Addiction Scale ratings were correlated with increased RSFCs of the Hb–thalamus and Hb–hypothalamus, respectively. The bidirectional relationships between Hb GMV and RSFC of the Hb–insula contributed to reduced BMI. Conclusions These findings indicate that LSG increased Hb GMV and that its related improvement in RSFC of the Hb–insula may mediate long-term benefits of LSG for eating behaviors and weight loss.