Reverse-translational identification of a cerebellar satiation network.

The brain is the seat of body weight homeostasis. However, our inability to control the increasing prevalence of obesity highlights a need to look beyond canonical feeding pathways to broaden our understanding of body weight control1-3. Here we used a reverse-translational approach to identify and anatomically, molecularly and functionally characterize a neural ensemble that promotes satiation. Unbiased, task-based functional magnetic resonance imaging revealed marked differences in cerebellar responses to food in people with a genetic disorder characterized by insatiable appetite. Transcriptomic analyses in mice revealed molecularly and topographically -distinct neurons in the anterior deep cerebellar nuclei (aDCN) that are activated by feeding or nutrient infusion in the gut. Selective activation of aDCN neurons substantially decreased food intake by reducing meal size without compensatory changes to metabolic rate. We found that aDCN activity terminates food intake by increasing striatal dopamine levels and attenuating the phasic dopamine response to subsequent food consumption. Our study defines a conserved satiation centre that may represent a novel therapeutic target for the management of excessive eating, and underscores the utility of a 'bedside-to-bench' approach for the identification of neural circuits that influence behaviour.

Modifying diet and exercise in multiple sclerosis (MoDEMS): A randomized controlled trial for behavioral weight loss in adults with multiple sclerosis and obesity.

BACKGROUND: Obesity is a risk factor for developing multiple sclerosis (MS) and MS-related disability. The efficacy of behavioral weight loss interventions among people with MS (pwMS) remains largely unknown. OBJECTIVE: Examine whether a group-based telehealth weight loss intervention produces clinically significant weight loss in pwMS and obesity. METHODS: Seventy-one pwMS were randomized to the weight loss intervention or treatment-as-usual (TAU). The 6-month program promoted established guidelines for calorie reduction and increased physical activity. Anthropometric measurements, mobility tasks, self-report questionnaires, and accelerometry were used to assess changes at follow-up. RESULTS: Mean percent weight loss in the treatment group was 8.6% compared to 0.7% in the TAU group (p < .001). Sixty-five percent of participants in the intervention achieved clinically meaningful weight loss (⩾ 5%). Participants in the treatment group engaged in 46.2 minutes/week more moderate-to-vigorous physical activity than TAU participants (p = .017) and showed improvements in quality of life (p = .012). Weight loss was associated with improved mobility (p = .003) and reduced fatiguability (p = .008). CONCLUSION: Findings demonstrate the efficacy of a behavioral intervention for pwMS and obesity, with clinically significant weight loss for two-thirds of participants in the treatment condition. Weight loss may also lead to improved mobility and quality of life.

Pediatric Tube Weaning: A Meta-Analysis of Factors Contributing to Success.

Approximately 3-10% of children have severe feeding issues, and some require enteral/tube nutrition to grow and thrive. For many children, tube feeding is temporary, making efficacious interventions for tube weaning essential. We conducted a systematic review and meta-analysis of tube weaning treatments. Outcomes included percentage of participants completely weaned from the tube, and mean percentage of kilocalories consumed orally following treatment. Data were extracted from 42 studies, including cohort studies and single-subject research design studies. We evaluated moderators of treatment success, including treatment setting, use of behavioral approaches, use of hunger provocation, and use of a multidisciplinary approach. Results indicated that, after treatment, children received significantly more calories orally, and 67-69% of children were fully weaned. These analyses suggest that current interventions are generally effective; however, variability within treatments exist. Prospective randomized clinical trials are needed to understand effective components of weaning interventions.

Unhealthy foods taste better among children with lower self-control.

Self-control is important for healthy eating. Achieving and maintaining healthy eating behaviors can be challenging for children. Susceptibility to palatable unhealthy foods with high sugar, fat, and/or salt is a biologically predisposed, dominant response that can hinder healthy eating decisions. Self-control can help adults to build automatized strategies for resisting susceptibility to unhealthy foods. Likewise, if self-control helps children to learn strategies for resisting susceptibility to unhealthy foods, susceptibility to unhealthy foods would be demonstrated in children with low self-control. Specifically, the association between unhealthiness and tastiness (i.e., unhealthy foods taste better) is one of the important mechanisms underlying susceptibility to unhealthy foods. We expected susceptibility to unhealthy foods to be indicated by the association between unhealthiness and tastiness, as well as better taste perception of unhealthy foods and unhealthy food preferences. In our study, fifty-nine children aged 8-13 years reported their perceived self-control, and completed computerized food rating tasks measuring their healthiness, taste, and preference ratings on 30 healthy and 30 unhealthy foods. Results showed that children with lower self-control demonstrated heightened susceptibility to unhealthy foods, but children with higher self-control did not. Our findings suggested that higher levels of self-control would help children to develop healthy eating strategies for regulating dispositional susceptibility to unhealthy foods.

Food commercials do not affect energy intake in a laboratory meal but do alter brain responses to visual food cues in children.

Food commercials promote snack intake and alter food decision-making, yet the influence of exposure to food commercials on subsequent neural processing of food cues and intake at a meal is unclear. This study tested whether exposing children to food or toy commercials altered subsequent brain response to high- and low-energy dense food cues and influenced laboratory intake at a multi-item, ad libitum meal. Forty-one 7-9-year-old children (25 healthy weight; 16 with overweight/obesity) completed five visits as part of a within-subjects design where they consumed multi-item test-meals under three conditions: no exposure, food commercial exposure, and toy commercial exposure. On the fourth and fifth visits, functional magnetic resonance imaging (fMRI) was performed while children viewed low- and high-energy dense food images following exposure to either food or toy commercials. Linear mixed models tested for differences in meal energy intake by commercial condition. A whole-brain analysis was conducted to compare differences in response by commercial condition and child weight status. Meal intake did not differ by commercial condition (p = 0.40). Relative to toy commercials, food commercials reduced brain response to high-energy food stimuli in cognitive control regions, including bilateral superior temporal gyri, middle temporal gyrus, and inferior frontal gyrus. Commercial condition * weight status interactions were observed in orbitofrontal cortex, fusiform gyrus, and supramarginal gyrus. Children with overweight/obesity showed increased response in these regions to high-energy stimuli following food commercials. Food commercial exposure affected children's subsequent processing of food cues by reducing engagement of the prefrontal cortex, a region implicated in cognitive control. Even though food commercial exposure did not increase intake at a meal, the effect of reduced prefrontal cortical engagement on a broader range of consumption patterns warrants investigation.

Time spent looking at food during a delay of gratification task is positively associated with children's consumption at ad libitum laboratory meals.

Greater ability to delay gratification for an immediate food reward may protect against the development of obesity. However, it is not known if the behaviors children exhibit during a delay of gratification task are related to overeating in other contexts. The purpose of this analysis was to assess the relationship between observed child coping strategies during a delay of gratification task and laboratory intake from ad libitum test-meals. The sample consisted of 40, 7-9 year old children (40% (N = 16 with overweight/obesity). Across 5 laboratory visits, children consumed 3 identical test-meals presented after varying exposure conditions (i.e., no exposure, exposure to food commercials, exposure to toy commercials). On the first visit, children were recorded during a delay of gratification task which was coded for three behavioral themes: looking at vs. away from food, talking vs. staying silent, and fidgeting vs. sitting still. Pearson correlations and multiple regressions were run to look at the relationships between coping strategies and test-meal intake. Time spent looking away from food was negatively associated with ad libitum food consumption at the meals. Conversely, greater time spent looking at food was positively associated with ad libitum food consumption. These relationships were independent of covariates likely to influence intake (e.g., sex, age, weight status, parent income) and were more robust following food rather than toy commercial exposure. Children who spent more time looking at food and less time looking away during a delay of gratification task may be vulnerable to overeating in other contexts. Upon replication in larger samples, these behaviors could serve as modifiable targets in the development of childhood obesity prevention programs.

Calorie Labeling Promotes Dietary Self-Control by Shifting the Temporal Dynamics of Health- and Taste-Attribute Integration in Overweight Individuals.

Understanding why people make unhealthy food choices and how to promote healthier choices is critical to prevent obesity. Unhealthy food choices may occur when individuals fail to consider health attributes as quickly as taste attributes in their decisions, and this bias may be modifiable by health-related external cues. One hundred seventy-eight participants performed a mouse-tracking food-choice task with and without calorie information. With the addition of calorie information, participants made healthier choices. Without calorie information, the initial integration of health attributes in overweight individuals' decisions was about 230 ms delayed relative to the taste attributes, but calorie labeling promoted healthier choices by speeding up the integration of health attributes during a food-choice task. Our study suggests that obesogenic choices are related to the relative speed with which taste and health attributes are integrated into the decision process and that this bias is modifiable by external health-related cues.

The Influence of Televised Food Commercials on Children's Food Choices: Evidence from Ventromedial Prefrontal Cortex Activations.

OBJECTIVE: To investigate how food commercials influence children's food choices. STUDY DESIGN: Twenty-three children ages 8-14 years provided taste and health ratings for 60 food items. Subsequently, these children were scanned with the use of functional magnetic resonance imaging while making food choices (ie, "eat" or "not eat") after watching food and nonfood television commercials. RESULTS: Our results show that watching food commercials changes the way children consider the importance of taste when making food choices. Children did not use health values for their food choices, indicating children's decisions were largely driven by hedonic, immediate rewards (ie, "tastiness"); however, children placed significantly more importance on taste after watching food commercials compared with nonfood commercials. This change was accompanied by faster decision times during food commercial trials. The ventromedial prefrontal cortex, a reward valuation brain region, showed increased activity during food choices after watching food commercials compared with after watching nonfood commercials. CONCLUSION: Overall, our results suggest watching food commercials before making food choices may bias children's decisions based solely on taste, and that food marketing may systematically alter the psychological and neurobiologic mechanisms of children's food decisions.

Being Kind to Your Future Self: Probability Discounting of Health Decision-Making.

INTRODUCTION: Nearly 50 % of patients with chronic medical illness exhibit poor treatment adherence. When making treatment decisions, these patients must balance the probability of current side effects against the probability of long-term benefits. This study examines if the behavioral economic construct of probability discounting can be used to explain treatment decisions in chronic disease. METHODS: Thirty-eight nonadherent and 39 adherent patients with multiple sclerosis (MS) completed a series of hypothetical treatment scenarios with varied risk and benefit probabilities. RESULTS: As described by a hyperbolic probability discounting model, all patients reported decreased medication initiation as the probability of treatment efficacy decreased and the probability of treatment side effects increased. When compared to adherent patients, nonadherent patients significantly devalued treatment efficacy and inflated treatment risk. DISCUSSION: The methods in this study can be used to identify optimal risk/benefit ratios for treatment development and inform the process by which patients make treatment decisions.

Healthy eating decisions require efficient dietary self-control in children: A mouse-tracking food decision study.

Learning how to make healthy eating decisions, (i.e., resisting unhealthy foods and consuming healthy foods), enhances physical development and reduces health risks in children. Although healthy eating decisions are known to be challenging for children, the mechanisms of children's food choice processes are not fully understood. The present study recorded mouse movement trajectories while eighteen children aged 8-13 years were choosing between eating and rejecting foods. Children were inclined to choose to eat rather than to reject foods, and preferred unhealthy foods over healthy foods, implying that rejecting unhealthy foods could be a demanding choice. When children rejected unhealthy foods, mouse trajectories were characterized by large curvature toward an eating choice in the beginning, late decision shifting time toward a rejecting choice, and slowed response times. These results suggested that children exercised greater cognitive efforts with longer decision times to resist unhealthy foods, providing evidence that children require dietary self-control to make healthy eating-decisions by resisting the temptation of unhealthy foods. Developmentally, older children attempted to exercise greater cognitive efforts for consuming healthy foods than younger children, suggesting that development of dietary self-control contributes to healthy eating-decisions. The study also documents that healthy weight children with higher BMIs were more likely to choose to reject healthy foods. Overall, findings have important implications for how children make healthy eating choices and the role of dietary self-control in eating decisions.

Can't wait to lose weight? Characterizing temporal discounting parameters for weight-loss.

Obesity is often related to steeper temporal discounting, that is, higher decision impulsivity for immediate rewards over delayed rewards. However, previous studies have measured temporal discounting parameters through monetary rewards. The aim of this study was to develop a temporal discounting measure based on weight-loss rewards, which may help to understand decision-making mechanisms more closely related to body weight regulation. After having their heights and weights measured, healthy young adults completed the Monetary Choice Questionnaire (MCQ), and an adapted version of the MCQ, with weight-loss as a reward. Participants also completed self-reports that measure obesity-related cognitive variables. For 42 participants who expressed a desire to lose weight, weight-loss rewards were discounted over time and had a positive correlation with temporal discounting for monetary rewards. Higher temporal discounting for weight loss rewards (i.e., preference for immediate weight loss) showed correlations with beliefs that obesity is under obese persons' control and largely due to lack of willpower, while temporal discounting parameters for monetary rewards did not. Taken together, our weight loss temporal discounting measure demonstrated both convergent and divergent validity, which can be utilized for future obesity research and interventions.

Apples or candy? Internal and external influences on children's food choices.

The goal of this concise narrative review is to examine the current literature regarding endogenous and exogenous influences on youth food choices. Specifically, we discuss internal factors such as interoception (self-awareness) of pain and hunger, and neural mechanisms (neurofunctional aspects) of food motivation. We also explore external factors such as early life feeding experiences (including parenting), social influences (peers), and food marketing (advertising). We conclude with a discussion of the overlap of these realms and future directions for the field of pediatric food decision science.

Robust relation between temporal discounting rates and body mass.

When given the choice between $100 today and $110 in 1 week, certain people are more likely to choose the immediate, yet smaller reward. The present study examined the relations between temporal discounting rate and body mass while accounting for important demographic variables, depressive symptoms, and behavioral inhibition and approach. After having their heights and weights measured, 100 healthy adults completed the Monetary Choice Questionnaire, the Beck Depression Inventory-II, and the Behavioral Inhibition Scale/Behavioral Approach Scale. Overweight and obese participants exhibited higher temporal discounting rates than underweight and healthy weight participants. Temporal discounting rates decreased as the magnitude of the delayed reward increased, even when other variables known to impact temporal discounting rate (i.e., age, education level, and annual household income) were used as covariates. A higher body mass was strongly related to choosing a more immediate monetary reward. Additional research is needed to determine whether consideration-of-future-consequences interventions, or perhaps cognitive control interventions, could be effective in obesity intervention or prevention programs.

Food and non-alcoholic beverage marketing in children and adults: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

Food marketing impacts the food behaviors of children and adults, but the underpinning neural mechanisms are poorly understood. This systematic review and meta-analysis pooled evidence from neuroimaging studies of exposure to food marketing stimuli (vs. control) on brain activations in children and adults to clarify regions associated with responding. Databases were searched for articles published to March 2022. Inclusion criteria included human functional magnetic resonance imaging (fMRI) studies employing a contrast between a food marketing stimulus and a non-food/non-exposure control, published in English in a peer-reviewed journal, reporting whole brain (not Region of Interest [ROI] only) co-ordinates. Eleven studies met inclusion criteria, of which eight were included in the quantitative synthesis (Activation Likelihood Estimation [ALE] meta-analysis). Food marketing exposures (vs. controls) produced greater activation in two clusters lying across the middle occipital gyrus, lingual gyrus, and cuneus (cluster 1), and the postcentral gyrus, precentral gyrus, and the inferior parietal lobule/supramarginal gyrus (cluster 2). Brain responses to food marketing are most consistently observed in areas relating to visual processing, attention, sensorimotor activity, and emotional processing. Subgroup analyses (e.g., adults vs. children) were not possible because of the paucity of data, and sensitivity analyses highlighted some instability in the clusters; therefore, conclusions remain tentative pending further research.

Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study.

BACKGROUND: A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS. METHODS: Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI). RESULTS: Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05). CONCLUSIONS: The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.

Brain responses to food logos in obese and healthy weight children.

OBJECTIVE: To evaluate brain activation in response to common food and nonfood logos in healthy weight and obese children. STUDY DESIGN: Ten healthy weight children (mean body mass index in the 50th percentile) and 10 obese children (mean body mass index in the 97.9th percentile) completed self-report measures of self-control. They then underwent functional magnetic resonance imaging while viewing food and nonfood logos. RESULTS: Compared with the healthy weight children, obese children showed significantly less brain activation to food logos in the bilateral middle/inferior prefrontal cortex, an area involved in cognitive control. CONCLUSION: When shown food logos, obese children showed significantly less brain activation than the healthy weight children in regions associated with cognitive control. This provides initial neuroimaging evidence that obese children may be more vulnerable to the effects of food advertising.

Sensory processing issues in young children presenting to an outpatient feeding clinic.

OBJECTIVES: The aim of the study was to describe the relation between sensory issues and medical complexity in a series of patients presenting to an outpatient multidisciplinary feeding team for evaluation, by a standardized measure of sensory-processing abilities. METHODS: A retrospective chart review of all of the patients seen from 2004 to 2009 on 2 key variables: medical diagnostic category and short sensory profile (SSP) score. RESULTS: On the SSP, 67.6% of children scored in the clinical ("definite difference") range. The most common diagnostic categories were developmental (n = 23), gastrointestinal (n = 16), and neurological (n = 13). Behavioral and cardiorespiratory medical diagnostic categories were significantly related to SSP total score and SSP definite difference score. CONCLUSIONS: Children who present for feeding evaluation do indeed tend to have clinically elevated scores regarding sensory processing, and these elevated scores are significantly related to certain medical diagnostic categories. Future research is needed to determine why these significant relations exist as well as their implications for treatment of feeding-related issues.

Neurocomputational mechanisms of food and physical activity decision-making in male adolescents.

We examined the neurocomputational mechanisms in which male adolescents make food and physical activity decisions and how those processes are influenced by body weight and physical activity levels. After physical activity and dietary assessments, thirty-eight males ages 14-18 completed the behavioral rating and fMRI decision tasks for food and physical activity items. The food and physical activity self-control decisions were significantly correlated with each other. In both, taste- or enjoyment-oriented processes were negatively associated with successful self-control decisions, while health-oriented processes were positively associated. The correlation between taste/enjoyment and healthy attribute ratings predicted actual laboratory food intake and physical activities (2-week activity monitoring). fMRI data showed the decision values of both food and activity are encoded in the ventromedial prefrontal cortex, suggesting both decisions share common reward value-related circuits at the time of choice. Compared to the group with overweight/obese, the group with normal weight showed stronger brain activations in the cognitive control, multisensory integration, and motor control regions during physical activity decisions. For both food and physical activity, self-controlled decisions utilize similar computational and neurobiological mechanisms, which may provide insights into how to promote healthy food and physical activity decisions.

Pediatric Neural Changes to Physical and Emotional Pain After Intensive Interdisciplinary Pain Treatment: A Pilot Study.

Brain areas activated during pain can contribute to enhancing or reducing the pain experience, showing a potential connection between chronic pain and the neural response to pain in adolescents and youth. This study examined changes in brain activation associated with experiencing physical pain, and the observation of physical and emotional pain in others, by using functional magnetic resonance imaging (fMRI) before and after intensive interdisciplinary pain treatment (IIPT). Eighteen youth (age 14 to 18) with widespread chronic pain completed fMRI testing before and after IIPT to assess changes in brain activation in response to physical and emotional pain. Broadly, brain activation changes were observed in frontal, somatosensory, and limbic regions. These changes suggest improvements in descending pain modulation via thalamus and caudate, and the different pattern of brain activation after treatment suggests better discrimination between physical and emotional pain. Brain activation changes were also correlated with improvements in clinical outcomes of catastrophizing (reduced activation in right caudate, right mid-cingulate, and postcentral gyrus) and pain-related disability (increased activation in precentral gyrus, left hippocampus, right middle occipital cortex, and left superior frontal gyrus). These changes support interpretation that reduced brain protective responses to pain were associated with treatment-related improvements. This pilot study highlights the need for larger trials designed to better understand the brain mechanisms involved in pediatric widespread pain treatment.

Reinforcer pathology, probabilistic choice, and medication adherence in patients with multiple sclerosis.

The reinforcer pathology model posits that core behavioral economic mechanisms, including delay discounting and behavioral economic demand, underlie adverse health decisions and related clinical disorders. Extensions beyond substance use disorder and obesity, however, are limited. Using a reinforcer pathology framework, this study evaluates medical adherence decisions in patients with multiple sclerosis. Participants completed behavioral economic measures, including delay discounting, probability discounting, and a medication purchase task. A medical decision-making task was also used to evaluate how sensitivity to mild side effect risk and efficacy contributed to the likelihood of taking a hypothetical disease-modifying therapy. Less steep delay discounting and more intense (greater) medication demand were independently associated with greater adherence to the medication decision-making procedure. More generally, the pattern of interrelations between the medication-specific and general behavioral economic metrics was consistent with and contributes to the reinforcer pathology model. Additional research is warranted to expand these models to different populations and health behaviors, including those of a positive health orientation (i.e., medication adherence).