Working memory gating in obesity: Insights from a case-control fMRI study.

Computational models and neurophysiological data propose that a 'gating mechanism' coordinates distractor-resistant maintenance and flexible updating of working memory contents: While maintenance of information is mainly implemented in the prefrontal cortex, updating of information is signaled by phasic increases in dopamine in the striatum. Previous literature demonstrates structural and functional alterations in these brain areas, as well as differential dopamine transmission among individuals with obesity, suggesting potential impairments in these processes. To test this hypothesis, we conducted an observational case-control fMRI study, dividing participants into groups with and without obesity based on their BMI. We probed maintenance and updating of working memory contents using a modified delayed match to sample task and investigated the effects of SNPs related to the dopaminergic system. While the task elicited the anticipated brain responses, our findings revealed no evidence for group differences in these two processes, neither at the neural level nor behaviorally. However, depending on Taq1A genotype, which affects dopamine receptor density in the striatum, participants with obesity performed worse on the task. In conclusion, this study does not support the existence of overall obesity-related differences in working memory gating. Instead, we propose that potentially subtle alterations may manifest specifically in individuals with a 'vulnerable' genotype.

Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery.

BACKGROUND: Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery. METHODS: Patients (n = 47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 ± 11.6%) and poor responders (PR, EWL 24.0 ± SD 12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM). RESULTS: Mean BMI was 47.1 ± 6.2 kg/m² in PR (n = 21) and 28.9 ± 3.1 kg/m² in GR (n = 26, p < 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p > 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 min. The increase was stronger in GR compared to PR (GLP-1, PYY: Time x Group p < 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p < 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (Time x Group p < 0.05). GR showed significantly higher WM scores than PR (p < 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY plasma levels, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = -0.07 - 1.54), in mediation analyses. CONCLUSION: Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Better working memory performance in GR might be mediated by higher postprandial reduction in ghrelin plasma levels. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.

Self-reported intake of high-fat and high-sugar diet is not associated with cognitive stability and flexibility in healthy men.

Animal studies indicate that a high-fat/high-sugar diet (HFS) can change dopamine signal transmission in the brain, which could promote maladaptive behavior and decision-making. Such diet-induced changes may also explain observed alterations in the dopamine system in human obesity. Genetic variants that modulate dopamine transmission have been proposed to render some individuals more prone to potential effects of HFS. The objective of this study was to investigate the association of HFS with dopamine-dependent cognition in humans and how genetic variations might modulate this potential association. Using a questionnaire assessing the self-reported consumption of high-fat/high-sugar foods, we investigated the association with diet by recruiting healthy young men that fall into the lower or upper end of that questionnaire (low fat/sugar group: LFS, n = 45; high fat/sugar group: HFS, n = 41) and explored the interaction of fat and sugar consumption with COMT Val158Met and Taq1A genotype. During functional magnetic resonance imaging (fMRI) scanning, male participants performed a working memory (WM) task that probes distractor-resistance and updating of WM representations. Logistic and linear regression models revealed no significant difference in WM performance between the two diet groups, nor an interaction with COMT Val158Met or Taq1A genotype. Neural activation in task-related brain areas also did not differ between diet groups. Independent of diet group, higher BMI was associated with lower overall accuracy on the WM task. This cross-sectional study does not provide evidence for diet-related differences in WM stability and flexibility in men, nor for a predisposition of COMT Val158Met or Taq1A genotype to the hypothesized detrimental effects of an HFS diet. Previously reported associations of BMI with WM seem to be independent of HFS intake in our male study sample.

Nutrient scoring for the DEGS1-FFQ - from food intake to nutrient intake.

BACKGROUND: While necessary for studying dietary decision-making or public health, estimates of nutrient supply based on self-reported food intake are barely accessible or fully lacking and remain a challenge in human research. In particular, detailed information on dietary fiber is limited. In this study we introduce an automated openly available approach to assess self-reported nutrient intake for research purposes for a popular, validated German food frequency questionnaire (FFQ). METHODS: To this end, we i) developed and shared a code for assessing nutrients (carbohydrates, fat, protein, sugar, fiber, etc.) for 53 items of the quantitative, validated German DEGS1-FFQ questionnaire implementing expert-guided nutritional values of diverse sources with several raters. In a sample of individuals (nGUT-BRAIN = 61 (21 female) overweight, omnivorous), we ii) cross-validated nutrient intake of the last 7 days and the last 24 h and iii) computed test-retest reliability across two timepoints. Further, iv) we reported newly computed nutrient intake for two independent cross-sectional cohorts with continuous weight status and different dietary habits (nMensa = 134 (79 female, 1 diverse), nGREADT = 76 male). Exploratively, we v) correlated computed, energy-adjusted nutrient intake with anthropometric markers and HbA1c and vi) used linear mixed models to analyse the predictability of BMI and WHR by nutrient intake. RESULTS: In overweight adults (n = 61 (21 female), mean age 28.2 ± 6.5 years, BMI 27.4 ± 1.6 kg/m2) nutrient intakes were mostly within recommended reference nutrient ranges for both last 7 days and last 24 h. Recommended fiber intake was not reached and sugar intake was surpassed. Calculated energy intake was significantly higher from last 24 h than from last 7 days but energy-adjusted nutrient intakes did not differ between those timeframes. Reliability of nutrient values between last 7 days and 24 h per visit was moderate (Pearson's rhoall ≥ 0.33, rhomax = 0.62) and absolute agreement across two timepoints was low to high for 7 days (Pearson's rhomin = 0.12, rhomax = 0.64,) and low to moderate for 24 h (Pearson's rhomin = 0.11, rhomax = 0.45). Associations of dietary components to anthropometric markers showed distinct sex differences, with overall higher intake by males compared to females and only females presenting a negative association of BMI with fiber intake. Lastly, in the overweight sample (but not when extending the analysis to a wider BMI range of 18.6-36.4 kg/m2), we could confirm that higher BMI was predicted by lower energy-adjusted fiber intake and higher energy-adjusted fat intake (when adjusting for age, sex and physical activity) while higher WHR was predicted by higher energy intake. CONCLUSION: We provide an openly available tool to systematically assess nutrient intake, including fiber, based on self-report by a common German FFQ. The computed nutrient scores resembled overall plausible and reliable measures of nutrient intake given the known limitations of FFQs regarding over- or underreporting and suggest valid comparability when adjusting for energy intake. Our open code nutrient scoring can help to examine dietary intake in experimental studies, including dietary fiber, and can be readily adapted to other FFQs. Further validation of computed nutrients with biomarkers and nutrient-specific metabolites in serum, urine or feces will help to interpret self-reported dietary intake.

Preliminary evidence for an association between intake of high-fat high-sugar diet, variations in peripheral dopamine precursor availability and dopamine-dependent cognition in humans.

Obesity is associated with alterations in dopaminergic transmission and cognitive function. Rodent studies suggest that diets rich in saturated fat and refined sugars (HFS), as opposed to diets diets low in saturated fat and refined sugars (LFS), change the dopamine system independent of excessive body weight. However, the impact of HFS on the human brain has not been investigated. Here, we compared the effect of dietary dopamine depletion on dopamine-dependent cognitive task performance between two groups differing in habitual intake of dietary fat and sugar. Specifically, we used a double-blind within-subject cross-over design to compare the effect of acute phenylalanine/tyrosine depletion on a reinforcement learning and a working memory task, in two groups that are on opposite ends of the spectrum of self-reported HFS intake (low vs high intake: LFS vs HFS group). We tested 31 healthy young women matched for body mass index (mostly normal weight to overweight) and IQ. Depletion of peripheral precursors of dopamine reduced the working memory specific performance on the operation span task in the LFS, but not in the HFS group (P = 0.016). Learning from positive- and negative-reinforcement (probabilistic selection task) was increased in both diet groups after dopamine depletion (P = 0.049). As a secondary exploratory research question, we measured peripheral dopamine precursor availability (pDAP) at baseline as an estimate for central dopamine levels. The HFS group had a significantly higher pDAP at baseline compared to the LFS group (P = 0.025). Our data provide the first evidence indicating that the intake of HFS is associated with changes in dopamine precursor availability, which is suggestive of changes in central dopamine levels in humans. The observed associations are present in a sample of normal to overweight participants (ie, in the absence of obesity), suggesting that the consumption of a HFS might already be associated with altered behaviours. Alternatively, the effects of HFS diet and obesity might be independent.