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.

A randomized-controlled trial to evaluate the app-based multimodal weight loss program zanadio for patients with obesity.

OBJECTIVE: This study aimed to evaluate the effectiveness of the app-based, multimodal weight loss program zanadio. METHODS: A randomized-controlled trial was conducted from January 2021 to March 2022. A total of 150 adults with obesity were randomized into an intervention group and used zanadio for 1 year or into a wait list control group. The primary end point, weight change, and the secondary end points, quality of life, well-being, and waist to height ratio, were assessed every 3 months for up to 1 year via telephone interviews and online questionnaires. RESULTS: After 12 months, participants of the intervention group lost, on average, -7.75% (95% CI: -9.66% to -5.84%) of their initial weight, achieving a clinically relevant and statistically stronger weight reduction than the control group (mean = 0.00% [95% CI: -1.98% to 1.99%]). All secondary end points improved significantly in the intervention group, with significantly greater improvements in well-being and waist to height ratio than in the control group. CONCLUSIONS: This study showed that adults with obesity who have used zanadio achieved a significant and clinically relevant weight loss within 12 months and improved further obesity-related health variables compared with a control group. Because of its effectiveness and flexible applicability, the app-based multimodal treatment zanadio might alleviate the present care gap for patients with obesity in Germany.

Diminished reinforcement sensitivity in adolescence is associated with enhanced response switching and reduced coding of choice probability in the medial frontal pole.

Precisely charting the maturation of core neurocognitive functions such as reinforcement learning (RL) and flexible adaptation to changing action-outcome contingencies is key for developmental neuroscience and adjacent fields like developmental psychiatry. However, research in this area is both sparse and conflicted, especially regarding potentially asymmetric development of learning for different motives (obtain wins vs avoid losses) and learning from valenced feedback (positive vs negative). In the current study, we investigated the development of RL from adolescence to adulthood, using a probabilistic reversal learning task modified to experimentally separate motivational context and feedback valence, in a sample of 95 healthy participants between 12 and 45. We show that adolescence is characterized by enhanced novelty seeking and response shifting especially after negative feedback, which leads to poorer returns when reward contingencies are stable. Computationally, this is accounted for by reduced impact of positive feedback on behavior. We also show, using fMRI, that activity of the medial frontopolar cortex reflecting choice probability is attenuated in adolescence. We argue that this can be interpreted as reflecting diminished confidence in upcoming choices. Interestingly, we find no age-related differences between learning in win and loss contexts.

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.

Cortical Grey Matter Mediates Increases in Model-Based Control and Learning from Positive Feedback from Adolescence to Adulthood.

Cognition and brain structure undergo significant maturation from adolescence into adulthood. Model-based (MB) control is known to increase across development, which is mediated by cognitive abilities. Here, we asked two questions unaddressed in previous developmental studies. First, what are the brain structural correlates of age-related increases in MB control? Second, how are age-related increases in MB control from adolescence to adulthood influenced by motivational context? A human developmental sample (n = 103; age, 12-50, male/female, 55:48) completed structural MRI and an established task to capture MB control. The task was modified with respect to outcome valence by including (1) reward and punishment blocks to manipulate the motivational context and (2) an additional choice test to assess learning from positive versus negative feedback. After replicating that an age-dependent increase in MB control is mediated by cognitive abilities, we demonstrate first-time evidence that gray matter density (GMD) in the parietal cortex mediates the increase of MB control with age. Although motivational context did not relate to age-related changes in MB control, learning from positive feedback improved with age. Meanwhile, negative feedback learning showed no age effects. We present a first report that an age-related increase in positive feedback learning was mediated by reduced GMD in the parietal, medial, and dorsolateral prefrontal cortex. Our findings indicate that brain maturation, putatively reflected in lower GMD, in distinct and partially overlapping brain regions could lead to a more efficient brain organization and might thus be a key developmental step toward age-related increases in planning and value-based choice.SIGNIFICANCE STATEMENT Changes in model-based decision-making are paralleled by extensive maturation in cognition and brain structure across development. Still, to date the neuroanatomical underpinnings of these changes remain unclear. Here, we demonstrate for the first time that parietal GMD mediates age-dependent increases in model-based control. Age-related increases in positive feedback learning were mediated by reduced GMD in the parietal, medial, and dorsolateral prefrontal cortex. A manipulation of motivational context did not have an impact on age-related changes in model-based control. These findings highlight that brain maturation in distinct and overlapping cortical regions constitutes a key developmental step toward improved value-based choices.

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.

Feasibility and utility of amygdala neurofeedback.

Amygdala NeuroFeedback (NF) have the potential of being a valuable non-invasive intervention tool in many psychiatric disporders. However, the feasibility and best practices of this method have not been systematically examined. The current article presents a review of amygdala-NF studies, an analytic summary of study design parameters, and examination of brain mechanisms related to successful amygdala-NF performance. A meta-analysis of 33 publications showed that real amygdala-NF facilitates learned modulation compared to control conditions. In addition, while variability in study dsign parameters is high, these design choices are implicitly organized by the targeted valence domain (positive or negative). However, in most cases the neuro-behavioral effects of targeting such domains were not directly assessed. Lastly, re-analyzing six data sets of amygdala-fMRI-NF revealed that successful amygdala down-modulation is coupled with deactivation of the posterior insula and nodes in the Default-Mode-Network. Our findings suggest that amygdala self-modulation can be acquired using NF. Yet, additional controlled studies, relevant behavioral tasks before and after NF intervention, and neural 'target engagement' measures are critically needed to establish efficacy and specificity. In addition, the fMRI analysis presented here suggest that common accounts regarding the brain network involved in amygdala NF might reflect unsuccessful modulation attempts rather than successful modulation.

Metabolic Profile and Metabolite Analyses in Extreme Weight Responders to Gastric Bypass Surgery.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut microbiota composition and systemically released metabolites were analyzed in a cohort of extreme weight responders after RYGB. METHODS: Patients (n = 23) were categorized based on excess weight loss (EWL) at a minimum of two years after RYGB in a good responder (EWL 93 ± 4.3%) or a bad responder group (EWL 19.5 ± 13.3%) for evaluation of differences in metabolic outcome, eating behavior and gut microbiota taxonomy and metabolic activity. RESULTS: Mean BMI was 47.2 ± 6.4 kg/m2 in the bad vs. 26.6 ± 1.2 kg/m2 in the good responder group (p = 0.0001). We found no difference in hunger and satiety sensation, in fasting or postprandial gut hormone release, or in gut microbiota composition between both groups. Differences in weight loss did not reflect in metabolic outcome after RYGB. While fecal and circulating metabolite analyses showed higher levels of propionate (p = 0.0001) in good and valerate (p = 0.04) in bad responders, respectively, conjugated primary and secondary bile acids were higher in good responders in the fasted (p = 0.03) and postprandial state (GCA, p = 0.02; GCDCA, p = 0.02; TCA, p = 0.01; TCDCA, p = 0.02; GDCA, p = 0.05; GUDCA, p = 0.04; TLCA, p = 0.04). CONCLUSIONS: Heterogenous weight loss response to RYGB surgery separates from patients' metabolic outcome, and is linked to unique serum metabolite signatures post intervention. These findings suggest that the level of adiposity reduction alone is insufficient to assess the metabolic success of RYGB surgery, and that longitudinal metabolite profiling may eventually help us to identify markers that could predict individual adiposity response to surgery and guide patient selection and counseling.

Molecular Imaging of Central Dopamine in Obesity: A Qualitative Review across Substrates and Radiotracers.

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics.

Brain response to food odors is not associated with body mass index and obesity-related metabolic health measures.

Smell perception plays a role in eating behavior and might be involved in the development of obesity. In fact, olfactory function is impaired in obesity and might depend on metabolic health factors. To date, the underlying neural mechanisms remain unclear. Here, we investigate neural processing of food-related odors in normal-weight, overweight and obese individuals. Fifty-three young and healthy participants (28.8 ± 4.4 years, 27 female; 24 normal-weight, 10 overweight, and 19 obese) were presented with high- (chocolate, potato chips) and low-caloric (orange, cucumber) food odors during a functional magnetic resonance imaging (fMRI). We also assessed olfactory identification ability, body mass index (BMI), body fat percentage, insulin resistance, and leptin levels. In brief, olfactory perception of food odors was linked to brain activity in the entorhinal and piriform cortex, and the insula, hippocampus, and amygdala. Insulin resistance was negatively related to olfactory identification. Additionally, perception of sweet versus savory odors was related to a higher brain activity in the right middle/superior frontal gyrus. Finally, we found no effect of obesity status, BMI, metabolic factors, or body fat percentage on neural responses to food odors. Overall, this suggests that food odor processing might depend on factors other than body weight status or associated markers of metabolic health.

Gut microbiota link dietary fiber intake and short-chain fatty acid metabolism with eating behavior.

The gut microbiome has been speculated to modulate feeding behavior through multiple factors, including short-chain fatty acids (SCFA). Evidence on this relationship in humans is however lacking. We aimed to explore if specific bacterial genera relate to eating behavior, diet, and SCFA in adults. Moreover, we tested whether eating-related microbiota relate to treatment success in patients after Roux-en-Y gastric bypass (RYGB). Anthropometrics, dietary fiber intake, eating behavior, 16S-rRNA-derived microbiota, and fecal and serum SCFA were correlated in young overweight adults (n = 27 (9 F), 21-36 years, BMI 25-31 kg/m2). Correlated genera were compared in RYGB (n = 23 (16 F), 41-70 years, BMI 25-62 kg/m2) and control patients (n = 17 (11 F), 26-69 years, BMI 25-48 kg/m2). In young adults, 7 bacteria genera, i.e., Alistipes, Blautia, Clostridiales cluster XVIII, Gemmiger, Roseburia, Ruminococcus, and Streptococcus, correlated with healthier eating behavior, while 5 genera, i.e., Clostridiales cluster IV and XIVb, Collinsella, Fusicatenibacter, and Parabacteroides, correlated with unhealthier eating (all | r | > 0.4, FDR-corrected p < 0.05). Some of these genera including Parabacteroides related to fiber intake and SCFA, and to weight status and treatment response in overweight/obese patients. In this exploratory analysis, specific bacterial genera, particularly Parabacteroides, were associated with weight status and eating behavior in two small, independent and well-characterized cross-sectional samples. These preliminary findings suggest two groups of presumably beneficial and unfavorable genera that relate to eating behavior and weight status, and indicate that dietary fiber and SCFA metabolism may modify these relationships. Larger interventional studies are needed to distinguish correlation from causation.

Loss of control over eating: A systematic review of task based research into impulsive and compulsive processes in binge eating.

Recurring episodes of excessive food intake in binge eating disorder can be understood through the lens of behavioral control systems: patients repeat maladaptive behaviors against their explicit intent. Self-report measures show enhanced impulsivity and compulsivity in binge eating (BE) but are agnostic as to the processes that might lead to impulsive and compulsive behavior in the moment. Task-based neurocognitive investigations can tap into those processes. In this systematic review, we synthesize neurocognitive research on behavioral impulsivity and compulsivity in BE in humans and animals, published between 2010-2020. Findings on impulsivity are heterogeneous. Findings on compulsivity are sparse but comparatively consistent, indicating an imbalance of goal-directed and habitual control as well as deficits in reversal learning. We urge researchers to address heterogeneity related to mood states and the temporal dynamics of symptoms, to systematically differentiate contributions of body weight and BE, and to ascertain the validity and reliability of tasks. Moreover, we propose to further scrutinize the compulsivity findings to unravel the computational mechanisms of a potential reinforcement learning deficit.

Increased Brain Reward Responsivity to Food-Related Odors in Obesity.

OBJECTIVE: Food odors serve as powerful stimuli signaling the food quality and energy density and direct food-specific appetite and consumption. This study explored obesity-related brain activation in response to odors related to high- or low-energy-dense foods. METHODS: Seventeen participants with obesity (BMI > 30 kg/m2 ; 4 males and 13 females) and twenty-one with normal weight (BMI < 25 kg/m2 ; 9 males and 12 females) underwent a functional magnetic resonance imaging scan in which they received chocolate (high-energy-dense food) and cucumber (low-energy-dense food) odor stimuli. Participants' olfactory and gustatory functions were assessed by the "Sniffin' Sticks" and "Taste Strips" tests, respectively. RESULTS: Compared with normal-weight controls, participants with obesity had lower odor sensitivity (phenylethyl alcohol) and decreased odor discrimination ability. However, participants with obesity demonstrated greater brain activation in response to chocolate compared with cucumber odors in the bilateral inferior frontal operculum and cerebellar vermis, right ventral anterior insula extending to putamen, right middle temporal gyrus, and right supramarginal areas. CONCLUSIONS: The present study provides preliminary evidence that obesity is associated with heightened brain activation of the reward and flavor processing areas in response to chocolate versus cucumber odors, possibly because of the higher energy density and reinforcing value of chocolate compared with cucumber.

Reduced Olfactory Bulb Volume in Obesity and Its Relation to Metabolic Health Status.

Smell perception plays an important role in eating behavior and might be involved in body weight gain. Since a body of literature implies that olfactory perception and function is hampered in obesity, we here investigate neuroanatomical correlates of this phenomenon. We assessed olfactory bulb (OB) volume with magnetic resonance imaging in 67 healthy participants with a body mass index (BMI) from 18.9 to 45.4 kg/m2 (mean = 28.58 ± 6.64). Moreover, we obtained psychophysiological data on olfactory ability (Sniffin' Sticks, Food associated odor test) and self-report measurements on eating behavior. Additionally, we collected parameters associated with metabolic health in obesity (waist-hip ratio, waist-height ratio, leptin levels, body fat percentage, fat mass index, insulin resistance) to investigate recently proposed mechanistic explanatory models of why olfaction may be altered in obesity. We showed that OB volume was significantly lower in participants with obesity when compared to those of normal weight. Moreover, we found weak to moderate negative correlations between OB volume and BMI and related measures of metabolic health, especially leptin, body fat percentage, waist-height ratio and insulin resistance. However, neither OB volume nor BMI were related to olfactory function in our young and healthy sample. Nevertheless, our results provide first indications that obesity is associated with brain anatomical changes in the OBs.

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.

Dopamine release, diffusion and uptake: A computational model for synaptic and volume transmission.

Computational modeling of dopamine transmission is challenged by complex underlying mechanisms. Here we present a new computational model that (I) simultaneously regards release, diffusion and uptake of dopamine, (II) considers multiple terminal release events and (III) comprises both synaptic and volume transmission by incorporating the geometry of the synaptic cleft. We were able to validate our model in that it simulates concentration values comparable to physiological values observed in empirical studies. Further, although synaptic dopamine diffuses into extra-synaptic space, our model reflects a very localized signal occurring on the synaptic level, i.e. synaptic dopamine release is negligibly recognized by neighboring synapses. Moreover, increasing evidence suggests that cognitive performance can be predicted by signal variability of neuroimaging data (e.g. BOLD). Signal variability in target areas of dopaminergic neurons (striatum, cortex) may arise from dopamine concentration variability. On that account we compared spatio-temporal variability in a simulation mimicking normal dopamine transmission in striatum to scenarios of enhanced dopamine release and dopamine uptake inhibition. We found different variability characteristics between the three settings, which may in part account for differences in empirical observations. From a clinical perspective, differences in striatal dopaminergic signaling contribute to differential learning and reward processing, with relevant implications for addictive- and compulsive-like behavior. Specifically, dopaminergic tone is assumed to impact on phasic dopamine and hence on the integration of reward-related signals. However, in humans DA tone is classically assessed using PET, which is an indirect measure of endogenous DA availability and suffers from temporal and spatial resolution issues. We discuss how this can lead to discrepancies with observations from other methods such as microdialysis and show how computational modeling can help to refine our understanding of DA transmission.

The Aetiology of Olfactory Dysfunction and Its Relationship to Diet Quality.

People with olfactory loss may choose foods rich in sugar, salt and fat to compensate their loss-foods that constitute a Western-style diet (WSD). However, olfactory dysfunction has not been consistently linked to any particular type of dietary change. Here we considered whether the aetiology of olfactory dysfunction may affect consumption of a WSD. Two-hundred and twenty-two people with olfactory dysfunction of varying cause, were tested for chemosensory performance and their frequency of consumption of a WSD. There was no evidence of a link between a WSD and olfactory dysfunction at the aggregate level, but an aetiology-based approach revealed various patterns, showing both positive and negative associations between olfactory performance and consumption of a WSD. We suggest a number of reasons why, in certain cases, greater olfactory dysfunction may be linked to lower intakes of a WSD, and the role that different aetiologies may have in affecting choices for foods that may appeal following olfactory impairment.

Insulin Resistance Is Associated with Reduced Food Odor Sensitivity across a Wide Range of Body Weights.

The worldwide obesity epidemic is a major health problem driven by the modern food environment. Recently, it has been shown that smell perception plays a key role in eating behavior and is altered in obesity. However, the underlying mechanisms of this phenomenon are not well understood yet. Since the olfactory system is closely linked to the endocrine system, we hypothesized that hormonal shifts in obesity might explain this relationship. In a within-subject, repeated-measures design, we investigated sensitivity to a food and a non-food odor in the hungry and sated state in 75 young healthy (26 normal weight, 25 overweight, and 24 obese) participants (37 women). To determine metabolic health status and hormonal reactivity in response to food intake, we assessed pre- and postprandial levels of insulin, leptin, glucose, and ghrelin. Odor sensitivity did not directly depend on body weight status/body mass index (BMI) or hunger state. However, we could establish a strong negative mediating effect of insulin resistance on the relationship between BMI/waist-hip ratio and olfactory sensitivity for the food odor. These findings indicate an impact of metabolic health status on sensitivity to food odors. Our results contribute to a better understanding of the mechanisms behind altered smell perception in obesity.