Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial.

OBJECTIVE: Animal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome-gut-brain communication. However, little is known if these results are applicable to humans. Therefore, we tested the effects of high-dosed prebiotic fibre on reward-related food decision-making in a randomised controlled within-subject cross-over study and assayed potential microbial and metabolic markers. DESIGN: 59 overweight young adults (19 females, 18-42 years, body mass index 25-30 kg/m2) underwent functional task MRI before and after 14 days of supplementary intake of 30 g/day of inulin (prebiotics) and equicaloric placebo, respectively. Short chain fatty acids (SCFA), gastrointestinal hormones, glucose/lipid and inflammatory markers were assayed in fasting blood. Gut microbiota and SCFA were measured in stool. RESULTS: Compared with placebo, participants showed decreased brain activation towards high-caloric wanted food stimuli in the ventral tegmental area and right orbitofrontal cortex after prebiotics (preregistered, family wise error-corrected p <0.05). While fasting blood levels remained largely unchanged, 16S-rRNA sequencing showed significant shifts in the microbiome towards increased occurrence of, among others, SCFA-producing Bifidobacteriaceae, and changes in >60 predicted functional signalling pathways after prebiotic intake. Changes in brain activation correlated with changes in Actinobacteria microbial abundance and associated activity previously linked with SCFA production, such as ABC transporter metabolism. CONCLUSIONS: In this proof-of-concept study, a prebiotic intervention attenuated reward-related brain activation during food decision-making, paralleled by shifts in gut microbiota. TRIAL REGISTRATION NUMBER: NCT03829189.

The different areas of chronic stress and food addiction: Results from the LIFE-Adult-Study.

There is an empirical association between stress and symptoms of food addiction (FA), but it is still not clear which domains of stress are the most relevant when it comes to FA, limiting the ability of researchers and practitioners to address problematic eating-related health outcomes. In order to address this gap in the literature, we analysed how different domains of chronic stress are related to FA. We used data from a subsample of the LIFE-Adult-Study (N = 1172), a German cohort study. We conducted a linear regression analysis with stress domains (Trier Inventory for Chronic Stress, TICS) as predictors of FA (Yale Food Addiction Scale, YFAS). In the second regression analysis we included sociodemographic variables, personality, and smoking as control variables. There was a significant and positive association between Social Overload, Work Discontent, Excessive Demands from Work, and Chronic Worrying and FA. After adding control variables, only Social Overload, Excessive Demands from Work, and Chronic Worrying remained significant predictors. Connections between stress domains and FA can serve as starting points for the development of meaningful interventions that support individuals self-care strategies (Social Overload), complexity management (Excessive Demands from Work), and coping with negative emotions (Chronic Worrying).

Neurocognitive predictors of food memory in healthy adults - A preregistered analysis.

Memory processes have long been known to determine food choices (Rozin & Zellner, 1985) but recognition memory of food and its cognitive, homeostatic and neuroanatomical predictors are still largely understudied. 60 healthy, overweight, non-restrictive eating adults (20 females) took part in a food wanting and subsequent food recognition and lure discrimination task at four time points after a standardized breakfast shake. With advanced tractography of 3 T diffusion-weighted imaging data, we investigated the influence of the uncinate fasciculus' (UF) brain microstructure on the interplay of food wanting and memory processes. The analysis was preregistered in detail and conducted with Bayesian multilevel regression modeling. Target recognition (d') and lure discrimination (LDI) performance of food tended to be higher than of art images while single image food memory accuracy evidently dominated art memory. On this single item level, wanting enhanced recognition accuracy and caloric content enhanced food memory accuracy. The enhancement by reward anticipation was most pronounced during memory encoding. Subjective hunger level did not predict performance on the memory task. The microstructure of the UF did neither evidently affect memory performance outcomes nor moderate the wanting enhancement of the recognition accuracy. Interestingly, female participants outperformed males on the memory task, and individuals with stronger neuroticism showed poorer memory performance. We shed light on to date understudied processes in food decision-making: reward anticipation influenced recognition accuracy and food memory was enhanced by higher caloric content, both effects might shape food decisions. Our findings indicate that brain microstructure does not affect food decision processes in adult populations with overweight. We suggest extending investigation of this interplay to brain activity as well as to populations with eating behaviour disorders.

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 Standardized Clinical Data Harmonization Pipeline for Scalable AI Application Deployment (FHIR-DHP): Validation and Usability Study.

BACKGROUND: Increasing digitalization in the medical domain gives rise to large amounts of health care data, which has the potential to expand clinical knowledge and transform patient care if leveraged through artificial intelligence (AI). Yet, big data and AI oftentimes cannot unlock their full potential at scale, owing to nonstandardized data formats, lack of technical and semantic data interoperability, and limited cooperation between stakeholders in the health care system. Despite the existence of standardized data formats for the medical domain, such as Fast Healthcare Interoperability Resources (FHIR), their prevalence and usability for AI remain limited. OBJECTIVE: In this paper, we developed a data harmonization pipeline (DHP) for clinical data sets relying on the common FHIR data standard. METHODS: We validated the performance and usability of our FHIR-DHP with data from the Medical Information Mart for Intensive Care IV database. RESULTS: We present the FHIR-DHP workflow in respect of the transformation of "raw" hospital records into a harmonized, AI-friendly data representation. The pipeline consists of the following 5 key preprocessing steps: querying of data from hospital database, FHIR mapping, syntactic validation, transfer of harmonized data into the patient-model database, and export of data in an AI-friendly format for further medical applications. A detailed example of FHIR-DHP execution was presented for clinical diagnoses records. CONCLUSIONS: Our approach enables the scalable and needs-driven data modeling of large and heterogenous clinical data sets. The FHIR-DHP is a pivotal step toward increasing cooperation, interoperability, and quality of patient care in the clinical routine and for medical research.

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.

Effects of single plant-based vs. animal-based meals on satiety and mood in real-world smartphone-embedded studies.

Adopting plant-based diets high in fiber may reduce global warming and obesity prevalence. Physiological and psychological determinants of plant-based food intake remain unclear. As fiber has been linked with improved gut-brain signaling, we hypothesized that a single plant-based (vegetarian and vegan) compared to an animal-based (animal flesh) meal, would induce higher satiety, higher mood and less stress. In three large-scale smartphone-based studies, adults (nall = 16,379) ranked satiety and mood before and after meal intake. Meal intake induced satiety and higher mood. Plant-based meal choices did not explain differences in post-meal hunger. Individuals choosing a plant-based meal reported slightly higher mood before and smaller mood increases after the meal compared to those choosing animal-based meals. Protein content marginally mediated post-meal satiety, while gender and taste ratings had a strong effect on satiety and mood in general. We could not detect the profound effects of plant-based vs. animal-based meals on satiety and mood.

Impact of obesity and diet on brain structure and function: a gut-brain-body crosstalk.

Most societies witness an ever increasing prevalence of both obesity and dementia, a scenario related to often underestimated individual and public health burden. Overnutrition and weight gain have been linked with abnormal functionality of homoeostasis brain networks and changes in higher cognitive functions such as reward evaluation, executive functions and learning and memory. In parallel, evidence has accumulated that modifiable factors such as obesity and diet impact the gut-brain axis and modulate brain health and cognition through various pathways. Using neuroimaging data from epidemiological studies and randomised clinical trials, we aim to shed light on the underlying mechanisms and to determine both determinants and consequences of obesity and diet at the level of human brain structure and function. We analysed multimodal 3T MRI of about 2600 randomly selected adults (47 % female, 18-80 years of age, BMI 18-47 kg/m2) of the LIFE-Adult study, a deeply phenotyped population-based cohort. In addition, brain MRI data of controlled intervention studies on weight loss and healthy diets acquired in lean, overweight and obese participants may help to understand the role of the gut-brain axis in food craving and cognitive ageing. We find that higher BMI and visceral fat accumulation correlate with accelerated brain age, microstructure of the hypothalamus, lower thickness and connectivity in default mode- and reward-related areas, as well as with subtle grey matter atrophy and white matter lesion load in non-demented individuals. Mediation analyses indicated that higher visceral fat affects brain tissue through systemic low-grade inflammation, and that obesity-related regional changes translate into cognitive disadvantages. Considering longitudinal studies, some, but not all data indicate beneficial effects of weight loss and healthy diets such as plant-based nutrients and dietary patterns on brain ageing and cognition. Confounding effects of concurrent changes in other lifestyle factors or false positives might help to explain these findings. Therefore a more holistic intervention approach, along with open science tools such as data and code sharing, in-depth pre-registration and pooling of data could help to overcome these limitations. In addition, as higher BMI relates to increased head micro-movements during MRI, and as head motion in turn systematically induces image artefacts, future studies need to rigorously control for head motion during MRI to enable valid neuroimaging results. In sum, our results support the view that overweight and obesity are intertwined with markers of brain health in the general population, and that weight loss and plant-based diets may help to promote brain plasticity. Meta-analyses and longitudinal cohort studies are underway to further differentiate causation from correlation in obesity- and nutrition-brain research.

Dietary Fiber and WHO Food Categories Extension for the Food-Pics_Extended Database.

Well characterized databases used for experimental purposes with extensive meta-data are essential for conducting meaningful and comparable studies. The Food-pics_extended database (Blechert et al., 2019) is one example for a widely used food stimulus database (original publication Blechert et al., 2014: 285 citations, and 2019: 32 citations). Indeed, meta-data on low level and high level image characteristics is broad, yet fiber ratings are not included, limiting its use in diet-related studies. Therefore, we developed fiber ratings per item (n = 562 stimuli), based on mean values of four non-expert raters. Ratings show good reliability (ICC = 0.77) and meaningful ranges per food type (mean fiber per 100 g by food type minbeverages = 0.04 ± 0.04 g and max Ready-to-eat savories = 4.49 ± 1.58). The newly provided fiber ratings enrich the already valuable database and extend it by an important nutrient value for human and planetary health.

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.

Estimating the effect of a scanner upgrade on measures of grey matter structure for longitudinal designs.

Longitudinal imaging studies are crucial for advancing the understanding of brain development over the lifespan. Thus, more and more studies acquire imaging data at multiple time points or with long follow-up intervals. In these studies changes to magnetic resonance imaging (MRI) scanners often become inevitable which may decrease the reliability of the MRI assessments and introduce biases. We therefore investigated the difference between MRI scanners with subsequent versions (3 Tesla Siemens Verio vs. Skyra) on the cortical and subcortical measures of grey matter in 116 healthy, young adults using the well-established longitudinal FreeSurfer stream for T1-weighted brain images. We found excellent between-scanner reliability for cortical and subcortical measures of grey matter structure (intra-class correlation coefficient > 0.8). Yet, paired t-tests revealed statistically significant differences in at least 67% of the regions, with percent differences around 2 to 4%, depending on the outcome measure. Offline correction for gradient distortions only slightly reduced these biases. Further, T1-imaging based quality measures reflecting gray-white matter contrast systematically differed between scanners. We conclude that scanner upgrades during a longitudinal study introduce bias in measures of cortical and subcortical grey matter structure. Therefore, before upgrading a MRI scanner during an ongoing study, researchers should prepare to implement an appropriate correction method for these effects.

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.

Effects of bariatric surgery on functional connectivity of the reward and default mode network: A pre-registered analysis.

Obesity imposes serious health risks and involves alterations in resting-state functional connectivity of brain networks involved in eating behavior. Bariatric surgery is an effective treatment, but its effects on functional connectivity are still under debate. In this pre-registered study, we aimed to determine the effects of bariatric surgery on major resting-state brain networks (reward and default mode network) in a longitudinal controlled design. Thirty-three bariatric surgery patients and 15 obese waiting-list control patients underwent magnetic resonance imaging at baseline, after 6 and 12 months. We conducted a pre-registered whole-brain time-by-group interaction analysis, and a time-by-group interaction analysis on within-network connectivity. In exploratory analyses, we investigated the effects of weight loss and head motion. Bariatric surgery compared to waiting did not significantly affect functional connectivity of the reward network and the default mode network (FWE-corrected p > .05), neither whole-brain nor within-network. In exploratory analyses, surgery-related BMI decrease (FWE-corrected p = .041) and higher average head motion (FWE-corrected p = .021) resulted in significantly stronger connectivity of the reward network with medial posterior frontal regions. This pre-registered well-controlled study did not support a strong effect of bariatric surgery, compared to waiting, on major resting-state brain networks after 6 months. Exploratory analyses indicated that head motion might have confounded the effects. Data pooling and more rigorous control of within-scanner head motion during data acquisition are needed to substantiate effects of bariatric surgery on brain organization.

Resting-state connectivity within the brain's reward system predicts weight loss and correlates with leptin.

Weight gain is often associated with the pleasure of eating food rich in calories. This idea is based on the findings that people with obesity showed increased neural activity in the reward and motivation systems of the brain in response to food cues. Such correlations, however, overlook the possibility that obesity may be associated with a metabolic state that impacts the functioning of reward and motivation systems, which in turn could be linked to reactivity to food and eating behaviour and weight gain. In a study involving 44 female participants [14 patients with obesity, aged 20-63 years (mean: 42, SEM: 3.2 years), and 30 matched lean controls, aged 22-60 years (mean: 37, SEM: 1.8 years)], we investigated how ventromedial prefrontal cortex seed-to-voxel resting-state connectivity distinguished between lean and obese participants at baseline. We used the results of this first step of our analyses to examine whether changes in ventromedial prefrontal cortex resting-state connectivity over 8 months could formally predict weight gain or loss. It is important to note that participants with obesity underwent bariatric surgery at the beginning of our investigation period. We found that ventromedial prefrontal cortex-ventral striatum resting-state connectivity and ventromedial-dorsolateral prefrontal cortex resting-state connectivity were sensitive to obesity at baseline. However, only the ventromedial prefrontal cortex-ventral striatum resting-state connectivity predicted weight changes over time using cross-validation, out-of-sample prediction analysis. Such an out-of-sample prediction analysis uses the data of all participants of a training set to predict the actually observed data in one independent participant in the hold-out validation sample and is then repeated for all participants. In seeking to explain the reason why ventromedial pre-frontal cortex-ventral striatum resting-state connectivity as the central hub of the brain's reward and motivational system may predict weight change over time, we linked weight loss surgery-induced changes in ventromedial prefrontal cortex-ventral striatum resting-state connectivity to surgery-induced changes in homeostatic hormone regulation. More specifically, we focussed on changes in fasting state systemic leptin, a homeostatic hormone signalling satiety, and inhibiting reward-related dopamine signalling. We found that the surgery-induced increase in ventromedial prefrontal cortex-ventral striatum resting-state connectivity was correlated with a decrease in fasting-state systemic leptin. These findings establish the first link between individual differences in brain connectivity in reward circuits in a more tonic state at rest, weight change over time and homeostatic hormone regulation.

The Effect of Polyphenols on Working and Episodic Memory in Non-pathological and Pathological Aging: A Systematic Review and Meta-Analysis.

Life expectancy steadily increases, and so do age-associated diseases, leading to a growing population suffering from cognitive decline and dementia. Impairments in working memory (WM) and episodic memory (EM) are associated with an increased risk of developing dementia. While there are no effective pharmacological therapies to preserve or enhance cognition and to slow down the progression from mild memory complaints to dementia so far, plant-based nutrients including polyphenols have been suggested to exert beneficial effects on brain aging. This review studies whether supplementary polyphenols are effective in preserving or enhancing memory in both non-pathological and pathological aging, and whether there are polyphenol efficiency differences between WM and EM. A systematic literature search was conducted and 66 out of 294 randomized clinical trials with 20 participants or more per group, aged 40 years or older were included. These covered a daily intake of 35-1,600 mg polyphenols, e.g., flavonols, flavonoids, isoflovones, anthocyanins, and/or stilbenes, over the course of 2 weeks to 6.5 years duration. In total, around half of the studies reported a significantly improved performance after polyphenol administration compared to control, while three studies reported a worsening of performance, and the remainder did not observe any effects. According to pooled WM and EM meta-analysis of all memory outcomes reported in 49 studies, overall effect size for WM and EM indicated a significant small positive effect on EM and WM with similar estimates (b ~ 0.24, p < 0.001), with large study heterogeneity and significant Funnel asymmetry tests suggesting a positivity bias. These results remained similar when excluding studies reporting extremely large positive effect sizes from the meta-analyses. While Ginkgo biloba and isoflavones did not show benefits in subgroup meta-analyses, those suggested some effects in extracts containing anthocyanins, other flavonoids and resveratrol, again potentially resulting from publication bias. To conclude, a systematic review and meta-analysis indicate that short- to moderate-term polyphenol interventions might improve WM and EM in middle-to older aged adults, however, publication bias in favor of positive results seems likely, rendering definite conclusions difficult. Future studies with larger, more diverse samples and sensitive monitoring of cardiovascular, metabolic and beginning brain pathologies as well as longer follow-up are needed to better understand the impact of age, (beginning) pathologies, gender, and long-term use on polyphenol action.

Less Animal-Based Food, Better Weight Status: Associations of the Restriction of Animal-Based Product Intake with Body-Mass-Index, Depressive Symptoms and Personality in the General Population.

Restricting animal-based products from diet may exert beneficial effects on weight status; however, less is known about such a diet and emotional health. Moreover, personality traits, for example high neuroticism, may contribute to restrictive eating habits and potentially confound diet-health associations. We aim to systematically assess if restrictive dietary intake of animal-based products relates to lower weight and higher depressive symptoms, and if differences in personality traits play a significant role. Cross-sectional data from the baseline LIFE-Adult study were collected from 2011-2014 in Leipzig, Germany (n = 8943). Main outcomes of interest were dietary frequency of animal-derived products in the last year measured using a Food Frequency Questionnaire (FFQ), body-mass-index (BMI) (kg/m2), and the Center of Epidemiological Studies Depression Scale (CES-D). Personality traits were assessed in a subsample of n = 7906 using the Five Factor Inventory (NEO-FFI). Higher restriction of animal-based product intake was associated with a lower BMI, but not with depression scores. Personality, i.e., lower extraversion, was related to lower frequency of animal product intake. Moreover, personality traits were significantly associated with depressive symptoms, i.e., higher neuroticism, lower extraversion, lower agreeableness, lower conscientiousness, and with higher BMI. These findings encourage future longitudinal studies to test the efficacy of restricting animal-based products as a preventive and therapeutic strategy for overweight and obesity.

art.pics Database: An Open Access Database for Art Stimuli for Experimental Research.

While art is omnipresent in human history, the neural mechanisms of how we perceive, value and differentiate art has only begun to be explored. Functional magnetic resonance imaging (fMRI) studies suggested that art acts as secondary reward, involving brain activity in the ventral striatum and prefrontal cortices similar to primary rewards such as food. However, potential similarities or unique characteristics of art-related neuroscience (or neuroesthetics) remain elusive, also because of a lack of adequate experimental tools: the available collections of art stimuli often lack standard image definitions and normative ratings. Therefore, we here provide a large set of well-characterized, novel art images for use as visual stimuli in psychological and neuroimaging research. The stimuli were created using a deep learning algorithm that applied different styles of popular paintings (based on artists such as Klimt or Hundertwasser) on ordinary animal, plant and object images which were drawn from established visual stimuli databases. The novel stimuli represent mundane items with artistic properties with proposed reduced dimensionality and complexity compared to paintings. In total, 2,332 novel stimuli are available open access as "art.pics" database at https://osf.io/BTWNQ/ with standard image characteristics that are comparable to other common visual stimuli material in terms of size, variable color distribution, complexity, intensity and valence, measured by image software analysis and by ratings derived from a human experimental validation study [n = 1,296 (684f), age 30.2 ± 8.8 y.o.]. The experimental validation study further showed that the art.pics elicit a broad and significantly different variation in subjective value ratings (i.e., liking and wanting) as well as in recognizability, arousal and valence across different art styles and categories. Researchers are encouraged to study the perception, processing and valuation of art images based on the art.pics database which also enables real reward remuneration of the rated stimuli (as art prints) and a direct comparison to other rewards from e.g., food or money. Key Messages: We provide an open access, validated and large set of novel stimuli (n = 2,332) of standardized art images including normative rating data to be used for experimental research. Reward remuneration in experimental settings can be easily implemented for the art.pics by e.g., handing out the stimuli to the participants (as print on premium paper or in a digital format), as done in the presented validation task. Experimental validation showed that the art.pics' images elicit a broad and significantly different variation in subjective value ratings (i.e., liking, wanting) across different art styles and categories, while size, color and complexity characteristics remained comparable to other visual stimuli databases.

The effects of plant-based diets on the body and the brain: a systematic review.

Western societies notice an increasing interest in plant-based eating patterns such as vegetarian and vegan, yet potential effects on the body and brain are a matter of debate. Therefore, we systematically reviewed existing human interventional studies on putative effects of a plant-based diet on the metabolism and cognition, and what is known about the underlying mechanisms. Using the search terms "plant-based OR vegan OR vegetarian AND diet AND intervention" in PubMed filtered for clinical trials in humans retrieved 205 studies out of which 27, plus an additional search extending the selection to another five studies, were eligible for inclusion based on three independent ratings. We found robust evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets (duration ≤ 24 months) on weight status, energy metabolism and systemic inflammation in healthy participants, obese and type-2 diabetes patients. Initial experimental studies proposed novel microbiome-related pathways, by which plant-based diets modulate the gut microbiome towards a favorable diversity of bacteria species, yet a functional "bottom up" signaling of plant-based diet-induced microbial changes remains highly speculative. In addition, little is known, based on interventional studies about cognitive effects linked to plant-based diets. Thus, a causal impact of plant-based diets on cognitive functions, mental and neurological health and respective underlying mechanisms has yet to be demonstrated. In sum, the increasing interest for plant-based diets raises the opportunity for developing novel preventive and therapeutic strategies against obesity, eating disorders and related comorbidities. Still, putative effects of plant-based diets on brain health and cognitive functions as well as the underlying mechanisms remain largely unexplored and new studies need to address these questions.

Cross-Species Immune Recognition Between Plasmodium vivax Duffy Binding Protein Antibodies and the Plasmodium falciparum Surface Antigen VAR2CSA.

Background: In pregnancy, Plasmodium falciparum parasites express the surface antigen VAR2CSA, which mediates adherence of red blood cells to chondroitin sulfate A (CSA) in the placenta. VAR2CSA antibodies are generally acquired during infection in pregnancy and are associated with protection from placental malaria. We observed previously that men and children in Colombia also had antibodies to VAR2CSA, but the origin of these antibodies was unknown. Here, we tested whether infection with Plasmodium vivax is an alternative mechanism of acquisition of VAR2CSA antibodies. Methods: We analyzed sera from nonpregnant Colombians and Brazilians exposed to P. vivax and monoclonal antibodies raised against P. vivax Duffy binding protein (PvDBP). Cross-reactivity to VAR2CSA was characterized by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry, and antibodies were tested for inhibition of parasite binding to CSA. Results: Over 50% of individuals had antibodies that recognized VAR2CSA. Affinity-purified PvDBP human antibodies and a PvDBP monoclonal antibody recognized VAR2CSA, showing that PvDBP can give rise to cross-reactive antibodies. Importantly, the monoclonal antibody inhibited parasite binding to CSA, which is the primary in vitro correlate of protection from placental malaria. Conclusions: These data suggest that PvDBP induces antibodies that functionally recognize VAR2CSA, revealing a novel mechanism of cross-species immune recognition to falciparum malaria.

Effects of rising amyloidß levels on hippocampal synaptic transmission, microglial response and cognition in APPSwe/PSEN1M146V transgenic mice.

BACKGROUND: Progression of Alzheimer's disease is thought initially to depend on rising amyloidß and its synaptic interactions. Transgenic mice (TASTPM; APPSwe/PSEN1M146V) show altered synaptic transmission, compatible with increased physiological function of amyloidß, before plaques are detected. Recently, the importance of microglia has become apparent in the human disease. Similarly, TASTPM show a close association of plaque load with upregulated microglial genes. METHODS: CA1 synaptic transmission and plasticity were investigated using in vitro electrophysiology. Microglial relationship to plaques was examined with immunohistochemistry. Behaviour was assessed with a forced-alternation T-maze, open field, light/dark box and elevated plus maze. FINDINGS: The most striking finding is the increase in microglial numbers in TASTPM, which, like synaptic changes, begins before plaques are detected. Further increases and a reactive phenotype occur later, concurrent with development of larger plaques. Long-term potentiation is initially enhanced at pre-plaque stages but decrements with the initial appearance of plaques. Finally, despite altered plasticity, TASTPM have little cognitive deficit, even with a heavy plaque load, although they show altered non-cognitive behaviours. INTERPRETATION: The pre-plaque synaptic changes and microglial proliferation are presumably related to low, non-toxic amyloidß levels in the general neuropil and not directly associated with plaques. However, as plaques grow, microglia proliferate further, clustering around plaques and becoming phagocytic. Like in humans, even when plaque load is heavy, without development of neurofibrillary tangles and neurodegeneration, these alterations do not result in cognitive deficits. Behaviours are seen that could be consistent with pre-diagnosis changes in the human condition. FUNDING: GlaxoSmithKline; BBSRC; UCL; ARUK; MRC.