Evaluation and follow-up of cognitive function and reward bias in obesity, and their biopsychosocial determinants: A prospective study of obese patients before and after bariatric surgery

Objectives: Obesity, defined by excess accumulation of body fat in the body, is a chronic disease that increases the risk of medical conditions such as hypertension and diabetes, in addition to mental disorders such as depression, and also mortality. Obese people are at increased risk of dementia and are more likely to have cognitive deficits. It is also argued that obese individuals have a reward dependence which makes them vulnerable to addictions other than food. Bariatric surgery (BS) is a preferred treatment for obesity because of its apparent effect on weight loss and recovery from concomitant diseases. It is not well known how BS affects the cognitive function and reward bias in obese patients in the early months post-surgery. Here it has been aimed to evaluate and monitor cognitive characteristics and reward responses of obese patients at baseline compared to healthy controls and before and after BS, along with determining associated psychiatric symptomatology and stress-related factors using computerized and standard measures, resting-state functional imaging, and potential biomarker measurements. Methods: 42 sleeve gastrectomy (SG) patients and 15 healthy controls were evaluated with self-report scales: Snaith-Hamilton Pleasure Scale (SHAPS), Cognitive Failures Scale (CFS), Mood Disorder Questionnaire, Barratt impulsivity, Beck Depression and Beck Anxiety scales to assess psychiatric symptomatology. BS patients were evaluated at baseline, and 3 months post-surgery. Healthy controls were assessed once. Participants completed laboratory-based measures of cognitive function (a neuropsychological test battery, Penn-CNP) and a reward learning task (the probabilistic reward task, PRT). Blood samples were collected at all assessments to assess HOMA-IR, HbA1c, CRP, lipid panel, vitamin B12, folic acid, and ferritin levels. 19 of the BS patients (pre-surgery and 3 months post-surgery) and 15 controls underwent resting-state functional magnetic resonance (fMRI) imaging for evaluation of functional connectivity (FC). The regions of interest on FC were default mode network (DMN), dorsal attention network, medial prefrontal cortex, hippocampus, nucleus accumbens, orbitofrontal cortex (OFC), caudate, putamen, amygdala, insular cortex, and salience network. Results: Depression, anxiety, impulsivity, stress, and anhedonia scores, in addition to self-report cognitive symptoms, did not change significantly at 3 months post-surgery compared to pre-surgery in obese patients. There was a significant increase in scores related to visuospatial perception and memory (32.53 ± 3.37 vs. 35.21 ± 3.80, p <0.001 for face memory task, 33.97 ± 3.59 vs. 35.92 ± 3.58, p =0.001 for delayed face memory task, 15.26 ± 2.59 vs. 16.13 ± 2.53, p=0.002 for visual object learning task) and visual attention and impulsivity (109.76 ± 12.18 vs. 114.56 ± 6.75, p=0.002 for continuous performance task) between pre-surgery and 3 months post-surgery, along with an increased overall performance score (-0.17 ± 0.81 vs. 0.29 ± 1.07, p<0.001). Mixed-effects regression analysis revealed that the model was a significant predictor of total correct responses for the visual object learning task (SVT). BMI negatively predicted SVT, while insulin resistance (HOMA-IR), C-reactive protein (CRP) and triglycerides did not. For the other improved cognitive scores, the model including BMI, HOMA-IR, CRP and triglycerides was not significant. There were no statistical differences between obese patients and healthy controls regarding Penn-CNP tasks scores at baseline. There was no significant difference in reward bias and discriminability variables, main outputs of the PRT, in the 3 months post-surgery in the obese group. When the obese patient group was compared with the healthy control group at baseline, obese patients had greater response bias (0.144 ± 0.225 vs. 0.072 ± 0.149, p=0.022) in PRT. Increased FC was found between the left hippocampus and precuneus cortex post-surgery in obese patients. There was a negative correlation between the change in total correct responses in the face memory task (IFAC_TOT) and the right PFC in the salience network in obese patients after BS. There were no FC differences in the DMN and in the major areas of the reward network, such as nucleus accumbens, putamen, ventromedial PFC, and the anterior insula post-surgery in the obese group. Significant FC changes were observed between obese patients and healthy controls. Right anterior insula FC with right supramarginal gyrus (SMG) and right OFC FC with right insular cortex were significantly higher and left amygdala FC with left precuneus was significantly lower in obese patients compared to controls. Also, left OFC FC with left frontal pole; left and right putamen FC with left middle and superior frontal gyrus were significantly lower and right intraparietal sulcus (IPS) with right postcentral gyrus was significantly higher in obese patients compared to controls. Conclusion: Bariatric surgery may cause improvement of cognitive task scores, even as early as three months post-surgery, however, reward bias in patients may remain unchanged. Our analysis shows that improvement of cognitive function may be devoid of the improvement of HOMA-IR, CRP, and triglyceride levels, but that it may relate to functional connectivity changes in the brain. Other biomarkers as GLP-1, leptin, ghrelin, and inflammatory cytokines might be mediating this relationship and it needs further assessment in conjunction with structural changes in the brain.