The effect of hunger state on hypothalamic functional connectivity in response to food cues.

The neural underpinnings of the integration of internal and external cues that reflect nutritional status are poorly understood in humans. The hypothalamus is a key integrative area involved in short- and long-term energy intake regulation. Hence, we examined the effect of hunger state on the hypothalamus network using functional magnetic resonance imaging. In a multicenter study, participants performed a food cue viewing task either fasted or sated on two separate days. We evaluated hypothalamic functional connectivity (FC) using psychophysiological interactions during high versus low caloric food cue viewing in 107 adults (divided into four groups based on age and body mass index [BMI]; age range 24-76 years; BMI range 19.5-41.5 kg/m2 ). In the sated compared to the fasted condition, the hypothalamus showed significantly higher FC with the bilateral caudate, the left insula and parts of the left inferior frontal cortex. Interestingly, we observed a significant interaction between hunger state and BMI group in the dorsolateral prefrontal cortex (DLPFC). Participants with normal weight compared to overweight and obesity showed higher FC between the hypothalamus and DLPFC in the fasted condition. The current study showed that task-based FC of the hypothalamus can be modulated by internal (hunger state) and external cues (i.e., food cues with varying caloric content) with a general enhanced communication in the sated state and obesity-associated differences in hypothalamus to DLPFC communication. This could potentially promote overeating in persons with obesity.

Associations between ghrelin and leptin and neural food cue reactivity in a fasted and sated state.

Food cue exposure can trigger eating. Food cue reactivity (FCR) is a conditioned response to food cues and includes physiological responses and activation of reward-related brain areas. FCR can be affected by hunger and weight status. The appetite-regulating hormones ghrelin and leptin play a pivotal role in homeostatic as well as hedonic eating. We examined the association between ghrelin and leptin levels and neural FCR in the fasted and sated state and the association between meal-induced changes in ghrelin and neural FCR, and in how far these associations are related to BMI and HOMA-IR. Data from 109 participants from three European centers (age 50±18 y, BMI 27±5 kg/m2) who performed a food viewing task during fMRI after an overnight fast and after a standardized meal were analyzed. Blood samples were drawn prior to the viewing task in which high-caloric, low-caloric and non-food images were shown. Fasting ghrelin was positively associated with neural FCR in the inferior and superior occipital gyrus in the fasted state. This was partly attributable to BMI and HOMA-IR. These brain regions are involved in visual attention, suggesting that individuals with higher fasting ghrelin have heightened attention to food cues. Leptin was positively associated with high calorie FCR in the medial prefrontal cortex (PFC) in the fasted state and to neural FCR in the left supramarginal gyrus in the fasted versus sated state, when correcting for BMI and HOMA-IR, respectively. This PFC region is involved in assessing anticipated reward value, suggesting that for individuals with higher leptin levels high-caloric foods are more salient than low-caloric foods, but foods in general are not more salient than non-foods. There were no associations between ghrelin and leptin and neural FCR in the sated state, nor between meal-induced changes in ghrelin and neural FCR. In conclusion, we show modest associations between ghrelin and leptin and neural FCR in a relatively large sample of European adults with a broad age and BMI range. Our findings indicate that people with higher leptin levels for their weight status and people with higher ghrelin levels may be more attracted to high caloric foods when hungry. The results of the present study form a foundation for future studies to test whether food intake and (changes in) weight status can be predicted by the association between (mainly fasting) ghrelin and leptin levels and neural FCR.

Gastric Emptying and Intragastric Behavior of Breast Milk and Infant Formula in Lactating Mothers.

BACKGROUND: When sufficient breast milk is not available, infant formula is often used as an alternative. As for digestion, gastric behavior of infant formula and breast milk have not been studied in detail. OBJECTIVE: This study aimed to compare gastric emptying and intragastric behavior between breast milk and infant formula in vivo using MRI. METHODS: In this randomized crossover study, 16 lactating mothers (age: 31.7 ± 2.9 y; time since giving birth: 9.3 ± 2 mo), underwent gastric MRI scans before and after consumption of 200 mL of infant formula or their own breast milk. MRI scans were performed after an overnight fast (baseline) and every 10 min up until 60 min following ingestion. Primary outcomes were gastric emptying measures and the secondary outcome was gastric layer volume over time. Differences between infant formula and breast milk in total gastric volume and layering volume were tested using linear mixed models. RESULTS: Gastric emptying half-time was 5.1 min faster for breast milk than for infant formula (95% CI: -19.0 to 29.2) (n = 14). Within a subgroup (n = 12) with similar initial gastric volume (<20 mL difference), gastric emptying half-time was 20 min faster for breast milk (95% CI: 1.23-43.1). Top layer volume (n = 16) was 6.4 mL greater for infant formula than for breast milk (95% CI: 1.9-10.8). This effect is driven by t = 10 and t = 20 min postingestion. CONCLUSIONS: When taking initial gastric volume into account, breast milk emptied faster than infant formula in women, which is in line with previous findings in infants. Infant formula showed a significantly larger top layer volume in the first 20 min after ingestion. MRI in adults may find application in studies assessing gastric behavior of infant formula.

Good taste or gut feeling? A new method in rats shows oro-sensory stimulation and gastric distention generate distinct and overlapping brain activation patterns.

Satiation is influenced by a variety of signals including gastric distention and oro-sensory stimulation. Here we developed a high-field (9.4 T) functional magnetic resonance imaging (fMRI) protocol to test how oro-sensory stimulation and gastric distention, as induced with a block-design paradigm, affect brain activation under different states of energy balance in rats. Repeated tasting of sucrose induced positive and negative fMRI responses in the ventral tegmental area and septum, respectively, and gradual neural activation in the anterior insula and the brain stem nucleus of the solitary tract (NTS), as revealed using a two-level generalized linear model-based analysis. These unique findings align with comparable human experiments, and are now for the first time identified in rats, thereby allowing for comparison between species. Gastric distention induced more extensive brain activation, involving the insular cortex and NTS. Our findings are largely in line with human studies that have shown that the NTS is involved in processing both visceral information and taste, and anterior insula in processing sweet taste oro-sensory signals. Gastric distention and sucrose tasting induced responses in mesolimbic areas, to our knowledge not previously detected in humans, which may reflect the rewarding effects of a full stomach and sweet taste, thereby giving more insight into the processing of sensory signals leading to satiation. The similarities of these data to human neuroimaging data demonstrate the translational value of the approach and offer a new avenue to deepen our understanding of the process of satiation in healthy people and those with eating disorders.

Development and body mass inversely affect children's brain activation in dorsolateral prefrontal cortex during food choice.

Childhood obesity is a rising problem caused in part by unhealthy food choices. Food choices are based on a neural value signal encoded in the ventromedial prefrontal cortex, and self-control involves modulation of this signal by the dorsolateral prefrontal cortex (dlPFC). We determined the effects of development, body mass (BMI Cole score) and body mass history on the neural correlates of healthy food choice in children. 141 children (aged 10-17y) from Germany, Hungary and Sweden were scanned with fMRI while performing a food choice task. Afterwards health and taste ratings of the foods were collected. In the food choice task children were asked to consider the healthiness or tastiness of the food or to choose naturally. Overall, children made healthier choices when asked to consider healthiness. However, children who had a higher weight gain per year chose less healthy foods when considering healthiness but not when choosing naturally. Pubertal development stage correlated positively while current body mass correlated negatively with dlPFC activation when accepting foods. Pubertal development negatively and current body mass positively influenced the effect of considering healthiness on activation of brain areas involved in salience and motivation. In conclusion, children in earlier stages of pubertal development and children with a higher body weight exhibited less activation in the dlPFC, which has been implicated in self-control during food choice. Furthermore, pubertal development and body mass influenced neural responses to a health cue in areas involved in salience and motivation. Thus, these findings suggest that children in earlier stages of pubertal development, children with a higher body mass gain and children with overweight may possibly be less susceptible to healthy eating interventions that rely on self-control or that highlight health aspects of food.

Brain Responses to Anticipation and Consumption of Beer with and without Alcohol.

Beer is a popular alcoholic beverage worldwide. Nonalcoholic beer (NA-beer) is increasingly marketed. Brain responses to beer and NA-beer have not been compared. It could be that the flavor of beer constitutes a conditioned stimulus associated with alcohol reward. Therefore, we investigated whether oral exposure to NA-beer with or without alcohol elicits similar brain responses in reward-related areas in a context where regular alcoholic beer is expected. Healthy men (n = 21) who were regular beer drinkers were scanned using functional MRI. Participants were exposed to word cues signaling delivery of a 10-mL sip of chilled beer or carbonated water (control) and subsequent sips of NA-beer with or without alcohol or water (control). Beer alcohol content was not signaled. The beer cue elicited less activation than the control cue in the primary visual cortex, supplementary motor area (reward-related region) and bilateral inferior frontal gyrus/frontal operculum. During tasting, there were no significant differences between the 2 beers. Taste activation after swallowing was significantly greater for alcoholic than for NA-beer in the inferior frontal gyrus/anterior insula and dorsal prefrontal cortex (superior frontal gyrus). This appears to be due to sensory stimulation by ethanol rather than reward processing. In conclusion, we found no differences in acute brain reward upon consumption of NA-beer with and without alcohol, when presented in a context where regular alcoholic beer is expected. This suggests that in regular consumers, beer flavor rather than the presence of alcohol is the main driver of the consumption experience.

Colouring perception: Package colour cues affect neural responses to sweet dairy drinks in reward and inhibition related regions.

Extrinsic product cues such as package colour may change product perception and perceived reward value during product evaluation. Healthier foods (i.e., 'light', sugar- or fat-reduced) often have different packages than regular products, e.g., they may be less vibrantly coloured. People vary in their degree of health-interest and self-control ability and may be affected differently by package colour. This study assesses the extent to which package colour and participant characteristics interact and influence product perception and brain responses. Thirty-four healthy females performed a functional MRI task in which they viewed four differently coloured packages (regular vs. healthier; differing in brightness and saturation levels) with or without simultaneously tasting a either a regular or a healthier calorie-reduced drink. Results indicate main effects of package and taste and a package*taste interaction effect. Compared to healthier packages viewing regular packages enhanced activation in region implicated in inhibitory control (inferior frontal gyrus) and a reward-related region (striatum), the latter even more so as participants' health interest increased (r = 0.43, p = 0.01). Incongruent package-taste combinations decreased activation in the orbitofrontal cortex (OFC, a region implicated in reward representation) compared to congruent combinations. Tasting the healthier compared to regular product enhanced activation in the middle and superior frontal gyrus, which are implicated in inhibitory control, as well as the striatum and OFC, suggesting a cognitively driven preference for the healthier product. In conclusion, this paper provides evidence for the conditions under which package colour and taste properties modulate neural correlates related to reward and inhibition. Individual differences in health-interest and impulsivity influence package- and taste-related neural correlates and thus underscore the importance of taking participant characteristics into account in food research.

Top-down expectation effects of food labels on motivation.

Labels on food packages inform our beliefs, shaping our expectations of food properties, such as its expected taste and healthiness. These beliefs can influence the processing of caloric rewards beyond objective sensory properties and have the potential to impact decision making. However, no studies, within or beyond the food domain, have assessed how written information, such as food labels, affect implicit motivation to obtain rewards, even though choices in daily life might be strongly driven by implicit motivational biases. We investigated how written information affects implicit motivation to obtain caloric rewards in healthy young adults. We used food labels (high- and low-calorie), associated with an identical fruit-flavored sugar-sweetened beverage, to study motivation for caloric rewards during fMRI. In a joystick task, hungry participants (N = 31) were instructed to make fast approach or avoid movements to earn the cued beverages. Behaviorally, we found a general approach bias, which was stronger for the beverage that was most preferred during a subsequent choice test, i.e., the one labeled as low-calorie. This behavioral effect was accompanied by increased BOLD signal in the sensorimotor cortex during the response phase of the task for the preferred, low-calorie beverage compared with the non-preferred, high-calorie beverage. During the anticipation phase, the non-preferred, high-calorie beverage label elicited stronger fMRI signal in the right ventral anterior insula, a region associated with aversion and taste intensity, than the preferred, low-calorie label. Together, these data suggest that high-calorie labeling can increase avoidance of beverages and reduce neural activity in brain regions associated with motor control. In conclusion, we show effects of food labeling on fMRI responses during anticipation and subsequent motivated action and on behavior, in the absence of objective taste differences, demonstrating the influence of written information on implicit biases. These findings contribute to our understanding of implicit biases in real-life eating behavior.

Severity of olfactory deficits is reflected in functional brain networks-An fMRI study.

Even though deficits in olfactory function affect a considerable part of the population, the neuronal basis of olfactory deficits remains scarcely investigated. To achieve a better understanding of how smell loss affects neural activation patterns and functional networks, we set out to investigate patients with olfactory dysfunction using functional magnetic resonance imaging (fMRI) and olfactory stimulation. We used patients' scores on a standardized olfactory test as continuous measure of olfactory function. 48 patients (mean olfactory threshold discrimination identification (TDI) score = 16.33, SD = 6.4, range 6 - 28.5) were investigated. Overall, patients showed piriform cortex activation during odor stimulation compared to pure sniffing. Group independent component analysis indicated that the recruitment of three networks during odor stimulation was correlated with olfactory function: a sensory processing network (including regions such as insula, thalamus and piriform cortex), a cerebellar network and an occipital network. Interestingly, recruitment of these networks during pure sniffing was related to olfactory function as well. Our results support previous findings that sniffing alone can activate olfactory regions. Extending this, we found that the severity of olfactory deficits is related to the extent to which neural networks are recruited both during olfactory stimulation and pure sniffing. This indicates that olfactory deficits are not only reflected in changes in specific olfactory areas but also in the recruitment of occipital and cerebellar networks. These findings pave the way for future investigations on whether characteristics of these networks might be of use for the prediction of disease prognosis or of treatment success.

Men and Women Differ in Gastric Fluid Retention and Neural Activation after Consumption of Carbonated Beverages.

Background: The most commonly consumed carbonated beverages are soda and beer. Carbon dioxide increases gastric volume, which can lead to epigastric discomfort. Women are more susceptible to this; however, correlations with neural activity and gastric distention are unknown. Objective: This study sought to determine the subjective, gastric, and neural correlates of epigastric discomfort in men and women. Methods: Thirty-four healthy, normal-weight adults [17 women; mean ± SD body mass index (BMI; kg/m2): 22.3 ± 1.9; 17 men; BMI: 22.8 ± 1.8] participated in a randomized crossover study with 2 treatments: ingestion of 500 mL beer or soda. Before and after consumption, gastric content and brain activity were measured with magnetic resonance imaging (MRI). Participants rated fullness, bloating, hunger, and nausea at baseline and at t = 0, 10, 20, and 30 min together with gastric MRI. Brain activity [cerebral blood flow (CBF)] was measured at baseline and at t = 5 and 35 min. Liquid, gas, and total gastric volume (TGV) were segmented from gastric MRI. Ratings and gastric content areas under the curve (AUCs) were tested with a mixed model with sex and drink as factors. Results: For subjective ratings, only nausea in the beer condition scored significantly greater for women (9.4-point increase; P = 0.045). Liquid stomach content was significantly greater for women (2525 mL × min increase; P = 0.019). In both men and women, the strongest correlation for bloating was with TGV (r = 0.45, P < 0.01) and for nausea was with the liquid fraction AUC (r = 0.45, P < 0.01). CBF changes did not differ between the drinks. Men showed greater CBF than women in the left precentral and postcentral gyri at t = 5 min. Conclusions: There are differences between sexes when it comes to appetite ratings, gastric fluid retention, and neural activation. Discomfort in women may be related to fluid rather than gas in the stomach, because they retain more fluid than men. Differences between men and women should be considered when studying digestion. This study was registered with the Dutch Trial Registry as NTR5418 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5418).

Considering healthiness promotes healthier choices but modulates medial prefrontal cortex differently in children compared with adults.

Childhood obesity is a rising problem worldwide mainly caused by overconsumption, which is driven by food choices. In adults, food choices are based on a value signal encoded in the medial prefrontal cortex (mPFC). This signal is modulated by the dorsolateral prefrontal cortex (dlPFC), which is involved in self-control. We aimed to examine the neural correlates of food choice in children, and how considering healthiness affects neural activity and choice behavior. 24 children and 28 adults performed a food choice task while being scanned with fMRI and provided health and taste ratings of the foods afterwards. During the choice task participants considered either the healthiness or tastiness of the food or chose naturally. Health rating was a positive predictor of choice in adults, but a negative predictor in children. Children had weaker dlPFC activation than adults during yes vs. no independent of health or taste condition. Both children and adults made healthier choices when considering healthiness. Taste rating modulated mPFC activation in both children and adults. When considering the healthiness, health rating positively modulated mPFC activation in adults, but negatively in children. Considering the healthiness increased connectivity between dlPFC and mPFC in adults, but not in children. In conclusion, considering healthiness can promote healthier choices in both children and adults, but is accompanied by an opposing pattern of brain activation in the mPFC. Since the absolute number of healthy choices remained lower in children, this suggests that children may not yet be geared to modify their choices away from their natural tendency to choose unhealthy tasty foods. Thus, this study suggests that it may be promising to develop interventions that increase children's preference for healthy food, for example by increasing the habitual consumption of healthy foods from a young age.

Food Decision-Making: Effects of Weight Status and Age.

Food decisions determine energy intake. Since overconsumption is the main driver of obesity, the effects of weight status on food decision-making are of increasing interest. An additional factor of interest is age, given the rise in childhood obesity, weight gain with aging, and the increased chance of type 2 diabetes in the elderly. The effects of weight status and age on food preference, food cue sensitivity, and self-control are discussed, as these are important components of food decision-making. Furthermore, the neural correlates of food anticipation and choice and how these are affected by weight status and age are discussed. Behavioral studies show that in particular, poor self-control may have an adverse effect on food choice in children and adults with overweight and obesity. Neuroimaging studies show that overweight and obese individuals have altered neural responses to food in brain areas related to reward, self-control, and interoception. Longitudinal studies across the lifespan will be invaluable to unravel the causal factors driving (changes in) food choice, overconsumption, and weight gain.

Standardized food images: A photographing protocol and image database.

The regulation of food intake has gained much research interest because of the current obesity epidemic. For research purposes, food images are a good and convenient alternative for real food because many dietary decisions are made based on the sight of foods. Food pictures are assumed to elicit anticipatory responses similar to real foods because of learned associations between visual food characteristics and post-ingestive consequences. In contemporary food science, a wide variety of images are used which introduces between-study variability and hampers comparison and meta-analysis of results. Therefore, we created an easy-to-use photographing protocol which enables researchers to generate high resolution food images appropriate for their study objective and population. In addition, we provide a high quality standardized picture set which was characterized in seven European countries. With the use of this photographing protocol a large number of food images were created. Of these images, 80 were selected based on their recognizability in Scotland, Greece and The Netherlands. We collected image characteristics such as liking, perceived calories and/or perceived healthiness ratings from 449 adults and 191 children. The majority of the foods were recognized and liked at all sites. The differences in liking ratings, perceived calories and perceived healthiness between sites were minimal. Furthermore, perceived caloric content and healthiness ratings correlated strongly (r ≥ 0.8) with actual caloric content in both adults and children. The photographing protocol as well as the images and the data are freely available for research use on http://nutritionalneuroscience.eu/. By providing the research community with standardized images and the tools to create their own, comparability between studies will be improved and a head-start is made for a world-wide standardized food image database.

What you see is what you eat: an ALE meta-analysis of the neural correlates of food viewing in children and adolescents.

Food cues are omnipresent and may enhance overconsumption. In the last two decades the prevalence of childhood obesity has increased dramatically all over the world, largely due to overconsumption. Understanding children's neural responses to food may help to develop better interventions for preventing or reducing overconsumption. We aimed to determine which brain regions are concurrently activated in children/adolescents in response to viewing food pictures, and how these relate to adult findings. Two activation likelihood estimation (ALE) meta-analyses were performed: one with studies in normal weight children/adolescents (aged 8-18, 8 studies, 137 foci) and one with studies in normal weight adults (aged 18-45, 16 studies, 178 foci). A contrast analysis was performed for children/adolescents vs. adults. In children/adolescents, the most concurrent clusters were in the left lateral orbitofrontal cortex (OFC), the bilateral fusiform gyrus, and the right superior parietal lobule. In adults, clusters in similar areas were found. Although the number of studies for a direct statistical comparison between the groups was relatively low, there were indications that children/adolescents may not activate areas important for cognitive control. Overall, the number of studies that contributed to the significant clusters was moderate (6-75%). In summary, the brain areas most consistently activated in children/adolescents by food viewing are part of the appetitive brain network and overlap with those found in adults. However, the age range of the children studied was rather broad. This study offers important recommendations for future research; studies making a direct comparison between adults and children in a sufficiently narrow age range would further elucidate how neural responses to food cues change during development.

Milk coagulation and gastric emptying in women experiencing gastrointestinal symptoms after ingestion of cow's milk.

BACKGROUND: Gastrointestinal symptoms after drinking milk are often attributed to lactose intolerance or cow's milk allergy. However, some individuals without either condition still report gastrointestinal symptoms after drinking milk. This may be caused by gastric emptying (GE) rate or gastric protein coagulation. This study aimed to compare GE rate and protein coagulation after milk consumption between individuals reporting gastrointestinal symptoms and those without symptoms using a novel gastric MRI approach. METHODS: Thirty women were included in this case-control study, of whom 15 reported gastrointestinal symptoms after drinking milk and 15 were controls. Participants underwent gastric MRI before and up to 90 min after consumption of 250 mL cow's milk. Gastric content volume and image texture of the stomach contents were used to determine GE and changes in the degree of coagulation. KEY RESULTS: GE half-time did not differ between the groups (gastrointestinal symptom group 66 ± 18 min; control group 61 ± 14 min, p = 0.845). The gastrointestinal symptom group reported symptoms from 30 min onwards and rated pain highest at 90 min. The control group reported no symptoms. Image texture analyses showed a significantly higher percentage of coagulum and lower percentage of liquid in the group in the GI symptom group (MD 11%, 95% CI [3.9, 17], p = 0.003). In vitro data suggests that pH and proteolytic enzyme activity influence the coagulum structure. CONCLUSIONS AND INFERENCES: Gastric milk coagulation and emptied fraction of stomach content may differ between individuals experiencing symptoms after milk consumption, possibly due to differences in pH and proteolytic enzyme activity.

Correction: Gastric coagulation and postprandial amino acid absorption of milk is affected by mineral composition: a randomized crossover trial.

Correction for 'Gastric coagulation and postprandial amino acid absorption of milk is affected by mineral composition: a randomized crossover trial' by Elise J. M. van Eijnatten et al., Food Funct., 2024, 15, 3098-3107, https://doi.org/10.1039/D3FO04063A.

Context matters: Neural processing of food-flavored e-cigarettes and the influence of smoking.

E-cigarettes are harmful, addictive, and popular. In e-cigarettes, nicotine is often paired with food-flavors. How this pairing of nicotine and food cues influences neural processing warrants investigation, as in smokers, both types of cues activate similar brain regions. Additionally, while most e-cigarettes are sweet, savory e-cigarettes are seemingly absent, although savory flavors are commonly liked in food. To understand how smoking status and type of flavor modulate reactions to food-flavored e-cigarettes, in comparison to actual food, neural and subjective responses to food odors were measured in a 2 (sweet vs. savory odor) x2 (food vs. e-cigarette context) x2 (smokers vs. non-smokers) design in 22 occasional/light smokers and 25 non-smokers. During fMRI scanning, participants were exposed to sweet and savory odors and pictures creating the two contexts. Liking and wanting were repeatedly measured on a 100-unit visual-analogue-scale. Results show that sweet e-cigarettes were liked (Δ = 14.2 ± 1.7) and wanted (Δ = 39.5 ± 3.1) more than savory e-cigarettes, and their cues activated the anterior cingulate more (cluster-level qFDR = 0.003). Further, we observed context-dependent variations in insula response to odors (cluster-level qFDR = 0.023, and = 0.030). Savory odors in an e-cigarette context were wanted less than the same odors in a food-context (Δ = 32.8 ± 3.1). Smokers and non-smokers reacted similarly to flavored product cues. Our results indicate that the principles of flavor preference in food cannot directly be applied to e-cigarettes and that it is challenging to design sweet and savory e-cigarettes to appeal to smokers only.

Gastric coagulation and postprandial amino acid absorption of milk is affected by mineral composition: a randomized crossover trial.

Background: In vitro studies suggest that casein coagulation of milk is influenced by its mineral composition, and may therefore affect the dynamics of protein digestion, gastric emptying and appearance of amino acids (AA) in the blood, but this remains to be confirmed in vivo. Objective: This study aimed to compare gastrointestinal digestion between two milks with the same total calcium content but different casein mineralization (CM). Design: Fifteen males (age 30.9 ± 13.8 years, BMI 22.5 ± 2.2 kg m-2) participated in this randomized cross-over study with two treatments. Participants underwent gastric magnetic resonance imaging (MRI) scans at the baseline and every 10 min up to 90 min after consumption of 600 ml milk with low or high CM. Blood samples were taken at the baseline and up to 5 hours postprandially. Primary outcomes were postprandial plasma AA concentrations and gastric emptying rate. Secondary outcomes were postprandial glucose and insulin levels, gastric coagulation as estimated by image texture metrics, and appetite ratings. Results: Gastric content volume over time was similar for both treatments. However, gastric content image analysis suggested that the liquid fraction emptied quicker in the high CM milk, while the coagulum emptied slower. Relative to high CM, low CM showed earlier appearance of AAs that are more dominant in casein, such as proline (MD 4.18 µmol L-1, 95% CI [2.38-5.98], p < 0.001), while there was no difference in appearance of AAs that are more dominant in whey protein, such as leucine. The image texture metrics homogeneity and busyness differed significantly between treatments (MD 0.007, 95% CI [0.001, 0.012], p = 0.022; MD 0.005, 95% CI [0.001, 0.010], p = 0.012) likely because of a reduced coagulation in the low CM milk. Conclusions: Mineral composition of milk can influence postprandial serum AA kinetics, likely due to differences in coagulation dynamics. The clinical trial registry number is NL8959 (https://clinicaltrials.gov).

The potential for clinical application of automatic quantification of olfactory bulb volume in MRI scans using convolutional neural networks.

The olfactory bulbs (OBs) play a key role in olfactory processing; their volume is important for diagnosis, prognosis and treatment of patients with olfactory loss. Until now, measurements of OB volumes have been limited to quantification of manually segmented OBs, which is a cumbersome task and makes evaluation of OB volumes in large scale clinical studies infeasible. Hence, the aim of this study was to evaluate the potential of our previously developed automatic OB segmentation method for application in clinical practice and to relate the results to clinical outcome measures. To evaluate utilization potential of the automatic segmentation method, three data sets containing MR scans of patients with olfactory loss were included. Dataset 1 (N = 66) and 3 (N = 181) were collected at the Smell and Taste Center in Ede (NL) on a 3 T scanner; dataset 2 (N = 42) was collected at the Smell and Taste Clinic in Dresden (DE) on a 1.5 T scanner. To define the reference standard, manual annotation of the OBs was performed in Dataset 1 and 2. OBs were segmented with a method that employs two consecutive convolutional neural networks (CNNs) that the first localize the OBs in an MRI scan and subsequently segment them. In Dataset 1 and 2, the method accurately segmented the OBs, resulting in a Dice coefficient above 0.7 and average symmetrical surface distance below 0.3 mm. Volumes determined from manual and automatic segmentations showed a strong correlation (Dataset 1: r = 0.79, p < 0.001; Dataset 2: r = 0.72, p = 0.004). In addition, the method was able to recognize the absence of an OB. In Dataset 3, OB volumes computed from automatic segmentations obtained with our method were related to clinical outcome measures, i.e. duration and etiology of olfactory loss, and olfactory ability. We found that OB volume was significantly related to age of the patient, duration and etiology of olfactory loss, and olfactory ability (F(5, 172) = 11.348, p < 0.001, R2 = 0.248). In conclusion, the results demonstrate that automatic segmentation of the OBs and subsequent computation of their volumes in MRI scans can be performed accurately and can be applied in clinical and research population studies. Automatic evaluation may lead to more insight in the role of OB volume in diagnosis, prognosis and treatment of olfactory loss.

Anterior cingulate taste activation predicts ad libitum intake of sweet and savory drinks in healthy, normal-weight men.

After food consumption, the motivation to eat (wanting) decreases and associated brain reward responses change. Wanting-related brain responses and how these are affected by consumption of specific foods are ill documented. Moreover, the predictive value of food-induced brain responses for subsequent consumption has not been assessed. We aimed to determine the effects of consumption of sweet and savory foods on taste activation in the brain and to assess how far taste activation can predict subsequent ad libitum intake. Fifteen healthy men (age: 27 ± 2 y, BMI: 22.0 ± 1.5 kg/m2) participated in a randomized crossover trial. After a >3-h fast, participants were scanned with the use of functional MRI before and after consumption of a sweet or savory preload (0.35 L fruit or tomato juice) on two occasions. After the scans, the preload juice was consumed ad libitum. During scanning, participants tasted the juices and rated their pleasantness. Striatal taste activation decreased after juice consumption, independent of pleasantness. Sweet and savory taste activation were not differentially affected by consumption. Anterior cingulate taste activation predicted subsequent ad libitum intake of sweet (r = -0.78; P < 0.001(uncorrected)) as well as savory juice (r = -0.70; P < 0.001(uncorrected)). In conclusion, we showed how taste activation of brain reward areas changes following food consumption. These changes may be associated with the food's physiological relevance. Further, the results suggest that anterior cingulate taste activation reflects food-specific satiety. This extends our understanding of the representation of food specific-appetite in the brain and shows that neuroimaging may provide objective and more accurate measures of food motivation than self-report measures.