Imaging Study On Laparoscopic Sleeve Gastrectomy Induced Changes In Habenular-related Brain Functional And Structural Connectivity

According to the“Report on the Nutrition and Chronic Diseases Status of Chinese Residents2020”,the percentage of overweight and obese subjects of Chinese adults was over 50.7%,and the growing obesity epidemic has become the third major death factor threatening people’s life and health.Obesity not only causes metabolic syndrome,cardiovascular disease and cancer,but also negatively affects brain cognitive function,diminishing the quality of life and increasing health care costs.The“Healthy China 2030”initiative,emphasizes reducing the growth rate of the overweight and obese population,guiding reasonable eating behaviors,and promoting physical and mental health.Thus,focusing on the pathogenesis and intervention mechanisms of obesity has clinical significance for combating severe obesity problems and improving population health.Long-term eating disorder and excessive intake of high-calorie foods play a crucial role in weight gain and obesity.Among the numerous factors inducing eating disorder,emotional eating is one of the primary causes,but the underlying neural mechanisms remain unclear.The habenular（Hb）,as a critical node to control antireward-based decision-making and emotions,not only participates in encoding attentional bias and motivational behaviors,but also has functional and structural connectivity（FC/SC）with regions/circuits associated with homeostatic and hedonic regulation.Disrupted interaction between the Hb and homeostatic/hedonic systems might promote emotional related eating disorder and cause obesity.Bariatric surgery,including laparoscopic sleeve gastrectomy（LSG）,is currently the most effective treatment for morbid obesity.Improved emotional eating behaviors are associated with weight-loss following surgery,suggesting that bariatric surgery may promote recovery of obesity-associated brain functional and structural abnormalities in regions involved with negative emotion processing.However,previous studies mainly focused on brain functional and structural abnormalities in regions involved with food reward and inhibitory control,few studies investigated Hb-related brain functional and structural changes and how bariatric surgery alters its FC/SC as well as the neural mechanisms in post-surgical weight loss.In the current study,we hypothesized that disrupted Hb connection could be a possible contributor for obesity,which might be associated with the disrupted interactions with regions involved with homeostatic/hedonic regulation,whereas bariatric surgery normalized these FCs/SCs,and would contribute to improved eating behaviors and long-term weight-loss.The primary innovates of this study are listed below:Firstly,the neuroimaging study on LSG-induced neuroplastic structural recovery in the Hb.Neuroimaging studies showed close associations between obesity and abnormal gray-matter volume（GMV）in brain regions involved with reward and inhibitory control,but little attention has been paid to the Hb and its association with negative emotional-related eating behaviors and body weight in patients with obesity.Therefore,we employed structural MRI and voxel-based morphometry analysis to assess obesity-related and LSG-induced changes in GMV in the Hb in 56 patients with obesity at pre-LSG（Pre LSG）and 12-months post-LSG(Post LSG₁₂),and compared them with 78 normal weight（NW）controls.Results showed that:1)LSG-induced whole brain GMV changes partially overlapped with those between Pre LSG and NW,including the Hb.2)Pre LSG relative to NW showed lower Hb GMV,whereas LSG had increased Hb GMV at Post LSG₁₂,which was equivalent to that in NW.3)Correlation analysis showed that increased Hb GMV was correlated with reduced body mass index（BMI）and disinhibition score following LSG.These findings suggested that LSG may promote neuroplastic structural recovery in the Hb,which might contribute to improved eating behaviors and weight-loss.Secondly,neuroimaging study on LSG-induced alterations in resting-state activity of Hb and related resting-state FC（RSFC）.Since LSG can promote recovery of obesity-related brain structural abnormalities in the Hb,we employed FC density（FCD）mapping and seed-based RSFC to examine obesity-related and LSG-induced alterations in the Hb in patients with obesity at Pre LSG and Post LSG₁₂,and in NW controls.Results showed that:1)Pre LSG relative to NW showed decreased FCD in the mediodorsal thalamic nucleus,Hb,superior/middle frontal gyri（SFG/MFG）,and increased FCD in the posterior cingulate cortex/precuneus,whereas LSG normalized these FCDs at Post LSG₁₂.2)Pre LSG relative to NW showed greater RSFCs of Hb-insula,Hb-precentral gyrus,Hb-rolandic＿oper,and weaker RSFCs of Hb-thalamus,Hb-hypothalamus（Hy）,and Hb-caudate,whereas LSG normalized these RSFCs at Post LSG₁₂.These changes in Hb-related RSFCs were associated with reduced BMI,Yale Food Addiction Scale score,emotional eating score,and hunger levels following LSG.3)Mediation analysis revealed that a bidirectional relationship between Hb GMV and RSFC of Hb-insula contributed to the reduced BMI at Post LSG₁₂.These findings suggested that LSG can promote recovery of obesity-related brain functional abnormalities in the Hb,which might be associated with enhanced sensitivity to hunger/satiety states,enhanced sensitivity to food aversion in non-hunger states,and rebalanced function in brain regions involved with homeostatic/hedonic regulation.Thirdly,neuroimaging study on LSG-induced improvement in SC of Hb-Hy and Hb-mesolimbic circuitry.Since LSG-induced improvement in RSFCs of Hb-homeostatic/hedonic circuits could serve as a biomarker for the long-term efficacy of LSG in appetite regulation and weight-loss,these SCs of Hb-homeostatic/hedonic circuits after LSG remains unclear.Therefore,we selected regions implicated in homeostatic/hedonic regulation that have anatomical connections with Hb as regions of interest,and used diffusion tensor imaging with probabilistic tractography to calculate SCs between the Hb and these regions of interest in patients with obesity at Pre LSG and Post LSG₁₂,and in NW controls.Results showed that:1)Pre LSG relative to NW showed decreased SCs between the Hb and homeostatic/hedonic regions including the Hy,bilateral SFG,left amygdala,and orbitofrontal cortex,whereas LSG increased these SCs at Post LSG₁₂.2)Correlation analysis showed that:at Pre LSG,SC of Hb-bilateral SFG were negatively correlated with disinhibition scores.At Post LSG₁₂,LSG-induced increases in SC of Hb-Hy were correlated with reduced depression and external eating scores;increased SC of Hb-left amygdala was correlated with reduced emotional eating scores;and increases in SC of Hb-left orbitofrontal cortex showed a negative correlation with reduced BMI.These findings suggested that LSG can promote recovery of obesity-related brain structural abnormalities in SCs of Hb-homeostatic/hedonic circuits,which may be associated with functional rebalancing in the Hb.Overall,LSG can promote recovery of obesity-related brain structural and functional abnormalities in the Hb,which might contribute to the improvement of negative emotional-related eating behaviors and weight-loss.The neural mechanisms underlying improvements in post-surgical eating behaviors may be related to enhanced sensitivity to food aversion in a non-hunger state,and related to rebalanced FCs/SCs between the Hb and regions/circuits involved with homeostatic/hedonic regulation,which would have an impact on the long-term benefits of LSG in appetite regulation and weight-loss.