Genetic associations with consumption of palatable foods in the absence of hunger in response to food cues in children.

OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations. METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms. RESULTS: Among 177 children, each FTO risk allele was associated with a 30% increase in gummy candy EAH (p = 0.025) in adjusted models. Food cue exposure exacerbated associations between the FTO variant with gummy candy EAH (p = 0.046). No statistically significant associations were found between MC4R and EAH. CONCLUSION: The results suggest children with the FTO rs9939609 risk allele may be predisposed to excess consumption of candy and that this association may be exacerbated by food cues.

Neural Responses to Auditory Food Stimuli Following Cognitive Behavioral Therapy for Binge-Eating Disorder.

OBJECTIVE: Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC). METHOD: Females with BED (N = 40) were randomized to CBT or WLC. Participants completed assessments at baseline and 16 weeks including measures of eating and appetite and functional magnetic resonance imaging (fMRI) to measure BOLD response while listening to personalized scripts of binge-eating and neutral-relaxing cues. Data were analyzed using general linear models with mixed effects. RESULTS: Overall retention rate was 87.5%. CBT achieved significantly greater reductions in binge-eating episodes than WLC (mean ± standard error decline of 14.6 ± 2.7 vs. 5.7 ± 2.8 episodes in the past 28 days, respectively; p = 0.03). CBT and WLC did not differ significantly in changes in neural responses to binge-eating stimuli during the fMRI sessions. Compared with WLC, CBT had significantly greater improvements in reward-based eating drive, disinhibition, and hunger as assessed by questionnaires (ps < 0.05). DISCUSSION: CBT was effective in reducing binge eating, but, contrary to our hypothesis, CBT did not improve BOLD response to auditory binge-eating stimuli in reward regions of the brain. Further studies are needed to assess mechanisms underlying improvements with CBT for BED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03604172.

The associations between attentional bias to food cues, parent-report appetitive traits, and concurrent adiposity among adolescents.

OBJECTIVE: To assess whether attentional bias to food cues and appetitive traits are independently and interactively associated with adiposity in adolescents. METHOD: Eighty-five adolescents, 14-17-years had their attentional bias to food images measured in a sated state by computing eye tracking measures of attention (first fixation duration, cumulative fixation duration) to food and control distractor images that bordered a computer game. Parents reported adolescent appetitive traits including the food approach domains of enjoyment of food, food responsiveness, emotional overeating, and the food avoidance domains of satiety responsiveness and emotional overeating through the Children's Eating Behavior Questionnaire. RESULTS: First fixation bias to food cues was positively associated with enjoyment of food, and negatively associated with satiety responsiveness. In a series of regression models adjusted for relevant covariates, first fixation bias to food cues (ß = 0.83, p = 0.007), higher food responsiveness (ß = 0.74, p < 0.001), higher emotional overeating (ß = 0.51, p = 0.002), and a composite appetite score (ß = 1.42, p < 0.001) were each significantly associated with greater BMI z-scores. In models assessing the interactive effects between attentional bias and appetitive traits, higher first fixation bias to food cues interacted synergistically with food responsiveness and emotional overeating in relation to BMI z-score. A synergistic interaction between first fixation bias to food cues and the composite appetite score in relation to BMI z-score was also observed. CONCLUSION: Individuals with high attentional bias to food cues and obesogenic appetitive traits may be particularly susceptible to weight gain.

The impact of poor fetal growth and chronic hyperpalatable diet exposure in adulthood on hippocampal function and feeding patterns in male rats.

Poor fetal growth affects eating behavior and the mesocorticolimbic system; however, its influence on the hippocampus has been less explored. Brain insulin sensitivity has been linked to developmental plasticity in response to fetal adversity and to cognitive performance following high-fat diet intake. We investigated whether poor fetal growth and exposure to chronic hyperpalatable food in adulthood could influence the recognition of environmental and food cues, eating behavior patterns, and hippocampal insulin signaling. At 60 days of life, we assigned male offspring from a prenatal animal model of 50% food restriction (FR) to receive either a high-fat and -sugar (HFS) diet or standard chow (CON) diet. Behavioral tests were conducted at 140 days, then tissues were collected. HFS groups showed a diminished hippocampal pAkt/Akt ratio. FR-CON and FR-HFS groups had higher levels of suppressor of cytokine signaling 3, compared to control groups. FR groups showed increased exploration of a novel hyperpalatable food, independent of their diet, and HFS groups exhibited overall lower entropy (less random, more predictable eating behavior) when the environment changed. Poor fetal growth and chronic HFS diet in adulthood altered hippocampal insulin signaling and eating patterns, diminishing the flexibility associated with eating behavior in response to extrinsic changes in food availability in the environment.

Does 'portion size' matter? Brain responses to food and non-food cues presented in varying amounts.

Larger portions of food elicit greater intake than smaller portions of food, particularly when foods are high in energy density (kcal/g; ED). The neural mechanisms underlying this effect remain unclear. The present study used fMRI to assess brain activation to food (higher-ED, lower-ED) and non-food (office supplies) images presented in larger and smaller (i.e., age-appropriate) amounts in 61, 7-8-year-olds (29 male, 32 female) without obesity. Larger amounts of food increased activation in bilateral visual and right parahippocampal areas compared to smaller amounts; greater activation to food amount (larger > smaller) in this cluster was associated with smaller increases in food intake as portions increased. Activation to amount (larger > smaller) was stronger for food than office supplies in primary and secondary visual areas, but, for office supplies only, extended into bilateral parahippocampus, inferior parietal cortex, and additional visual areas (e.g., V7). Activation was greater for higher-vs. lower-ED food images in ventromedial prefrontal cortex for both larger and smaller amounts of food; however, this activation extended into left lateral orbital frontal cortex for smaller amounts only. Activation to food cues did not differ by familial risk for obesity. These results highlight potentially distinct neural pathways for encoding food energy content and quantity.

CRH neurons in the lateral hypothalamic area regulate feeding behavior of mice.

Food cues serve as pivotal triggers for eliciting physiological responses that subsequently influence food consumption. The magnitude of response induced by these cues stands as a critical determinant in the context of obesity risk. Nonetheless, the underlying neural mechanism that underpins how cues associated with edible food potentiate feeding behaviors remains uncertain. In this study, we revealed that corticotropin-releasing hormone (CRH)-expressing neurons in the lateral hypothalamic area played a crucial role in promoting consummatory behaviors in mice, shedding light on this intricate process. By employing an array of diverse assays, we initially established the activation of these neurons during feeding. Manipulations using optogenetic and chemogenetic assays revealed that their activation amplified appetite and promoted feeding behaviors, whereas inhibition decreased them. Additionally, our investigation identified downstream targets, including the ventral tegmental area, and underscored the pivotal involvement of the CRH neuropeptide itself in orchestrating this regulatory network. This research casts a clarifying light on the neural mechanism underlying the augmentation of appetite and the facilitation of feeding behaviors in response to food cues. VIDEO ABSTRACT.

Energy deficiency promotes rhythmic foraging behavior by activating neurons in paraventricular hypothalamic nucleus.

Background: Dysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood. Methods: Home-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity. Results: We described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior. Discussion: These results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders.

No effect of hunger on attentional capture by food cues: Two replication studies.

Food cues potently capture human attention, and it has been suggested that hunger increases their propensity to do so. However, the evidence for such hunger-related attentional biases is weak. We focus on one recent study that did show significantly greater attentional capture by food cues when participants were hungry, using an Emotional Blink of Attention (EBA) task [Piech, Pastorino, & Zald, 2010. Appetite, 54, 579-582]. We conducted online (N = 29) and in-person (N = 28) replications of this study with British participants and a Bayesian analytical approach. For the EBA task, participants tried to identify a rotated target image in a Rapid Serial Visual Presentation (RSVP). Targets were preceded by "neutral", "romantic", or "food" distractor images. Participants completed the task twice, 6-11 days apart, once hungry (overnight plus 6h fast) and once sated (after a self-selected lunch in the preceding 1h). We predicted that food images would create a greater attentional blink when participants were hungry than when they were sated, but romantic and neutral images would not. We found no evidence that hunger increased attentional capture by food cues, despite our experiments passing manipulation and quality assurance checks. Our sample and stimuli differed from the study we were replicating in several ways, but we were unable to identify any specific factor responsible for the difference in results. The original finding may not be generalisable. The EBA is more sensitive to the physical distinctiveness of distractors from filler and target images than their emotional valence, undermining the sensitivity of the EBA task for picking up subtle changes in motivational state. Moreover, hunger-related attentional bias shifts may not be substantial over the intensities and durations of hunger typically induced in laboratory experiments.

Effects of a health versus hedonic mindset on daily-life snacking behaviour.

BACKGROUND: In today's obesogenic environment high-caloric palatable foods are omnipresent, making it hard for many to reach and maintain a healthy body weight. This study investigates the effects of a health versus hedonic mindset on daily-life snacking behaviour. The hypothesis is that a health mindset leads to reduced snacking behaviour compared to a hedonic mindset. This effect is expected to be most pronounced with high dietary restraint and least pronounced with high trait self-control. METHODS: For 3 weeks, degree of craving and amount of snacks that were craved and consumed were assessed four times a day, using smartphone Ecological Momentary Assessment (EMA). A total of 111 female participants (body mass index range: 20-23.5) were randomly assigned to a 1-week health (n = 53) or hedonic (n = 58) mindset, occurring in week 2 of the EMA protocol. The mindset manipulations consisted of text messages, focusing either on the enjoyment of tasty food (hedonic) or on healthy living and eating (health). RESULTS: contrary to our hypotheses, mindset did not affect snacking behaviour. Instead, degree of craving and intake of snacks reduced significantly over time, not moderated by mindset, dietary restraint (Restraint Scale) or trait self-control (Brief Self-Control Scale). Importantly, this was not due to reduced compliance. Possibly, the reduced craving and snacking behaviour were due to monitoring and/or socially desirable answering tendencies. Additional time point analyses showed that craving was strongest in the late afternoon (3:30-5:00 PM), and-across mindset conditions-degree of craving correlated negatively with trait self-control. CONCLUSIONS: future studies could manipulate degree of monitoring and design individually tailored manipulations.

Attentional bias for high-calorie food cues by the level of hunger and satiety in individuals with binge eating behaviors.

Introduction: The abnormal hyperreactivity to food cues in individuals with binge eating behaviors could be regulated by hedonic or reward-based system, overriding the homeostatic system. The aim of the present study was to investigate whether attentional bias for food cues is affected by the level of hunger, maintaining the normal homeostatic system in individuals with binge eating behaviors. Methods: A total of 116 female participants were recruited and divided into four groups: hungry-binge eating group (BE) (n = 29), satiated BE (n = 29), hungry-control (n = 29), satiated control (n = 29). While participants completed a free-viewing task on high or low-calorie food cues, visual attentional processes were recorded using an eye tracker. Results: The results revealed that BE group showed longer initial fixation duration toward high-calorie food cues in both hunger and satiety condition in the early stage, whereas the control group showed longer initial fixation duration toward high-calorie food cues only in hunger conditions. Moreover, in the late stage, the BE group stared more at the high-calorie food cue, compared to control group regardless of hunger and satiety. Discussion: The findings suggest that automatic attentional bias for food cues in individuals with binge eating behaviors occurred without purpose or awareness is not affected by the homeostatic system, while strategic attention is focused on high-calorie food. Therefore, the attentional processing of food cues in binge eating group is regulated by hedonic system rather than homeostatic system, leading to vulnerability to binge eating.

Associations between behavioral self-regulation and external food cue responsiveness (EFCR) in preschool-age children and evidence of modification by parenting style.

Decreased behavioral regulation is hypothesized to be a risk factor for excess weight gain among children, possibly via reduced appetite-specific regulation. Little research has specifically focused on behavioral regulation and food cue responsiveness, a conditioned precursor to eating, at a young age. This study examined the association between behavioral regulation and external food cue responsiveness among preschool-age children and explored if a more structured parenting style moderated that association. Baseline data from a prospective study on media use among preschool-age children (n = 83) in Northern New England were used. Parents reported on three domains of children's behavioral regulation (attentional focusing, inhibitory control, and emotional self-regulation), the children's external food cue responsiveness (EFCR), and their parenting styles (authoritative and permissive) via validated questionnaires. Mean age among children was 4.31 (SD 0.91) years, 57% of children were male, 89% were non-Hispanic white, and 26.2% had overweight or obesity. In a series of adjusted linear regression models, lower attentional focusing (standardized ß, ßs = -0.35, p = 0.001), inhibitory control (ßs = -0.30, p = 0.008), and emotional self-regulation (standardized beta, ßs = -0.38, p < 0.001) were each significantly associated with greater EFCR. In exploratory analyses, a more structured parenting style (more authoritative or less permissive) mitigated the associations between inhibitory control and EFCR (Bonferroni-adjusted p-interaction < 0.017). Findings support that lower attentional focusing, inhibitory control, and emotional self-regulation relate to greater ECFR in preschool-age children. The association between inhibitory control and EFCR may be modified by parenting style. Further research is needed to understand if children's responsiveness to external food cues may account for reported associations between lower behavioral regulation and adiposity gain over time.

The influence of physical activity on neural responses to visual food cues in humans: A systematic review of functional magnetic resonance imaging studies.

This systematic review examined whether neural responses to visual food-cues measured by functional magnetic resonance imaging (fMRI) are influenced by physical activity. Seven databases were searched up to February 2023 for human studies evaluating visual food-cue reactivity using fMRI alongside an assessment of habitual physical activity or structured exercise exposure. Eight studies (1 exercise training, 4 acute crossover, 3 cross-sectional) were included in a qualitative synthesis. Structured acute and chronic exercise appear to lower food-cue reactivity in several brain regions, including the insula, hippocampus, orbitofrontal cortex (OFC), postcentral gyrus and putamen, particularly when viewing high-energy-density food cues. Exercise, at least acutely, may enhance appeal of low-energy-density food-cues. Cross-sectional studies show higher self-reported physical activity is associated with lower reactivity to food-cues particularly of high-energy-density in the insula, OFC, postcentral gyrus and precuneus. This review shows that physical activity may influence brain food-cue reactivity in motivational, emotional, and reward-related processing regions, possibly indicative of a hedonic appetite-suppressing effect. Conclusions should be drawn cautiously given considerable methodological variability exists across limited evidence.

Eliciting real cravings with virtual food: Using immersive technologies to explore the effects of food stimuli in virtual reality.

In this paper, we explore the current technical possibilities of eating in virtual reality (VR) and show how this could be used to influence eating behaviors. Cue-based exposure therapy is a well-known method used to treat eating disorders. There are several benefits to using VR in combination with cue-based therapy. However, before VR-based cue-exposure can be used for therapeutic purposes, the ability of the VR environment to elicit craving responses in participants must be assessed. This was the objective of the first part of the study, where we assessed whether our VR environment elicited food craving responses in participants. Results showed that our VR environment elicited food craving responses: Salivation Magnitude, Food Craving State and Urge to Eat was significantly different from the neutral baseline. In addition, results showed that food cravings measured through the salivation magnitude in response to the virtual condition were not significantly different from the real condition, thus showing that VR had a comparable effect on producing food cravings. The second part of the study was conducted to determine whether the addition of olfactory and interaction cues in VR increased the development of food cravings. The results of this part showed that adding synthetic olfactory cues, paired with visual cues, to our system, provided a significant further increase in food cravings. Our results demonstrate that the use of food cues in VR can increase the development of food cravings and that it is possible to provide a simple yet convincing eating experience in VR. Inevitably, food interaction in VR is still underexplored territory and further research is needed to improve utility and application in disciplines related to food and eating.

Heightened sensitivity to high-calorie foods in children at risk for obesity: insights from behavior, neuroimaging, and genetics.

Pediatric obesity is a major public health concern. Genetic susceptibility and increased availability of energy-dense food are known risk factors for obesity. However, the extent to which these factors jointly bias behavior and neural circuitry towards increased adiposity in children remains unclear. While undergoing fMRI, 108 children (ages 5-11y) performed a food-specific go/no-go task. Participants were instructed to either respond ("go") or inhibit responding ("no-go") to images of food or toys. Half of the runs depicted high-calorie foods (e.g., pizza) whereas the other half depicted low-calorie foods (e.g., salad). Children were also genotyped for a DNA polymorphism associated with energy intake and obesity (FTO rs9939609) to examine the influence of obesity risk on behavioral and brain responses to food. Participants demonstrated differences in behavioral sensitivity to high- and low-calorie food images depending on task demands. Participants were slower but more accurate at detecting high- (relative to low-) calorie foods when responding to a neutral stimulus (i.e., toys) and worse at detecting toys when responding to high-calorie foods. Inhibition failures were accompanied by salience network activity (anterior insula, dorsal anterior cingulate cortex), which was driven by false alarms to food images. Children at a greater genetic risk for obesity (dose-dependent model of the FTO genotype) demonstrated pronounced brain and behavioral relationships such that genetic risk was associated with heightened sensitivity to high-calorie food images and increased anterior insula activity. These findings suggest that high-calorie foods may be particularly salient to children at risk for developing eating habits that promote obesity.

Perceived stress increases susceptibility to visual food cues in fast-food menu selections.

Individuals who report perceived stress often eat more unhealthy foods and more calories than those with lower stress levels, though individual differences and contexts are important. This study investigated how visual food cues on fast-food menus may increase calorie consumption intentions due to their potential motivational influences. A 2 (presence or absence of visual cues) x 4 (exemplar fast-food restaurant menu) fractionated experiment administered online (N = 325) indicated that when participants viewed menus with visual cues, they selected a greater number of calories to consume. Additionally, data showed an interaction effect of perceived stress and visual cues revealing that visual elements incentivized participants reporting higher stress to select more calories whereas visual cues did not have this effect for people reporting lower levels of perceived stress. Though important limitations exist, a key takeaway is that food cue exposure is another important factor to consider when predicting how stress may affect eating decisions.

Corrigendum: Differential neural reward reactivity in response to food advertising medium in children.

[This corrects the article DOI: 10.3389/fnins.2023.1052384.].

Differential neural reward reactivity in response to food advertising medium in children.

Introduction: Food cues including food advertisements (ads) activate brain regions related to motivation and reward. These responses are known to correlate with eating behaviors and future weight gain. The objective of this study was to compare brain responses to food ads by different types of ad mediums, dynamic (video) and static (images), to better understand how medium type impacts food cue response. Methods: Children aged 9-12 years old were recruited to complete a functional magnetic resonance imaging (fMRI) paradigm that included both food and non-food dynamic and static ads. Anatomical and functional images were preprocessed using the fMRIPrep pipeline. A whole-brain analysis and a targeted region-of-interest (ROI) analysis for reward regions (nucleus accumbens, orbitofrontal cortex, amygdala, insula, hypothalamus, ventral tegmental area, substantia nigra) were conducted. Individual neural responses to dynamic and static conditions were compared using a paired t-test. Linear mixed-effects models were then constructed to test the differential response by ad condition after controlling for age, sex, BMI-z, physical activity, and % of kcal consumed of a participant's estimated energy expenditure in the pre-load prior to the MRI scan. Results: A total of 115 children (mean=10.9 years) completed the fMRI paradigm. From the ROI analyses, the right and left hemispheres of the amygdala and insula, and the right hemisphere of the ventral tegmental area and substantia nigra showed significantly higher responses for the dynamic food ad medium after controlling for covariates and a false discovery rate correction. From the whole-brain analysis, 21 clusters showed significant differential responses between food ad medium including the precuneus, middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus, and all regions remained significant after controlling for covariates. Discussion: Advertising medium has unique effects on neural response to food cues. Further research is needed to understand how this differential activation by ad medium ultimately affects eating behaviors and weight outcomes.

Sex Differences in Effects of Mood, Eating-Related Behaviors, and BMI on Food Appeal and Desire to Eat: A Cross-Sectional Survey Study.

Although sex differences in food intake have been observed consistently, contributing factors are not well understood. Using a cross-sectional online survey (n = 306; 151 men, 155 women), this study aimed to assess how sex impacts relationships between food ratings (appeal/desire to eat for high-calorie (HC) and low-calorie (LC) food images) and eating-related attitudes/behaviors, body mass index (BMI), and mood. Across participants, increased state- and trait-based hunger, disinhibition, and cravings were associated with both increased HC appeal and desire (p < 0.001). Increased state-based hunger and cravings were associated with greater LC desire (p < 0.001). Greater satiety was associated with decreased desire for both HC and LC (p < 0.001), while greater anxiety was associated with increased desire for both HC and LC (p < 0.001). Significant associations between BMI and food ratings were not observed. Women reported greater dietary restraint, trait-based hunger, disinhibition, eating disorder-related behaviors, depression, and stress compared to men, in addition to greater appeal and familiarity with LC foods (all p < 0.05). Significant effects of sex on the associations between food ratings and eating-related attitudes/behaviors, BMI, and mood were not observed, however. Findings support the importance of considering mood and eating-related attitudes/behaviors in investigations of food cue responsivity.

Development and validation of the food cue responsivity scale.

Food cues are ubiquitous in today's environment; however, there is heterogeneity as to the extent to which these cues impact eating behavior among individuals. This study examines the validity and reliability of the Food Cue Responsivity Scale (FCRS) to assess responsivity to distinct types of food cues. Items gathered from existing measures were combined in the FCRS to reflect two subdomains, uncontrolled eating behavior and cognitive rumination. The criterion validity of the FCRS was established using a paradigm that assesses psychophysiological responsivity to a craved food among adults with overweight or obesity. Higher overall FCRS scores were associated with greater physiological responsivity to food exposures. These findings may help identify specific phenotypes of individuals with overweight or obesity with high responsivity to food cues, which could be used to understand overeating and response to weight-loss programs.

Characterizing motor impulsivity of individuals classified as overweight to obese.

Deficits in the impulse control system are an important predictor of energy intake and body weight. Adults classified as overweight to obese may possess these deficits as a general behavioral trait or they may be food-specific. The present study assessed motor impulsivity (ability to suppress a pre-potent response) when presented with food and neutral (non-food) cues, testing if deficits in motor impulsivity is specific to food cues or a general trait among participants classified as overweight to obese. The proportion of inhibitory failures to no-go targets following food cues (10.8%) was significantly greater than the proportion of inhibitory failures to no-go targets following neutral cues (1.9%, p â€‹< â€‹0.001). These differences remained when covering for sex and hunger. This indicates deficits in food-specific impulse control (as opposed to general impulse control) are present in those classified as overweight to obese. Understanding the specific aspect of impulse control that is present in this population is needed for the development of future impulse control training interventions that seek to change eating behaviors as a means for weight control.