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.

Using telehealth to assess depression and suicide ideation and provide mental health interventions to groups of chronically ill adolescents and young adults.

Telehealth distance health care is a significant resource for young, chronically ill patient populations given their numerous medical complexities and their concomitant depression and/or suicide ideation experiences. This manuscript shares the telehealth methods used to prepare for a larger study of interventions for increasing adolescents' and young adults' chronic care resiliency and skills for preventing depression. The young patients in this study were prescribed lifelong home parenteral nutrition infusions, treatment for those with short gut bowel diseases. The training methods for our mental health nurse and psychologist to conduct depression and suicide ideation assessments from a distance are presented. The study implementation methods of group facilitated interventions and discussion are reviewed. The group discussions were conducted via audiovisual telehealth devices over encrypted firewall-protected connections with patients in their own homes and professionals in an office. The results of assessments of the 40 participants, 25% (n = 10) with depressive symptoms or suicide ideation, are described. Following participants' assessments, their subsequent depression measures were all in the normal range, without any suicide ideation, across the year of the study. Patient evaluation ratings were high in the areas of being able to connect with other young patients in similar situations, using the audiovisual equipment, and learning new useful information from the interventions. The methods developed for the study ensured that the safety and well-being of participants were supported through telehealth.

Discontinuing Treatment Against Medical Advice: The Role of Perceived Autonomy Support From Providers in Relapsing-Remitting Multiple Sclerosis.

BACKGROUND: Long-term medication adherence is problematic among patients with chronic medical conditions. To our knowledge, this was the first study to examine factors associated with nonadherence among patients with relapsing-remitting multiple sclerosis who discontinue disease-modifying treatments against medical advice. PURPOSE: To examine differences in perceived provider autonomy support between disease-modifying treatment-adherent relapsing-remitting multiple sclerosis patients and relapsing-remitting multiple sclerosis patients who discontinued disease-modifying treatments against medical advice. METHODS: Self-report questionnaires and a neurologic exam were administered to demographically matched adherent (n = 50) and nonadherent (n = 79) relapsing- remitting multiple sclerosis patients from the Midwest and Northeast USA. RESULTS: Adherent patients reported greater perceived autonomy support from their treatment providers, F(1, 124) = 28.170, p < .001, partial η2 = .185. This difference persisted after controlling for current multiple sclerosis healthcare provider, education, disease duration, Expanded Disability Status Scale, perceived barriers to adherence, and prevalence of side effects, F(1, 121) = 9.61, p = .002, partial η2 = .074. Neither depressive symptoms, F(1, 124) = 1.001, p > .05, partial η2 = .009, nor the occurrence of a major depressive episode, χ2(1, N = 129) = .288, p > .05, differed between adherent and nonadherent patients. CONCLUSIONS: Greater perceived autonomy support from treatment providers may increase adherence to disease-modifying treatments among patients who discontinue treatment against medical advice. Results may inform interventions for patients who discontinue treatment against medical advice.

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.

Reasons for nonadherence and response to treatment in an adherence intervention trial for relapsing-remitting multiple sclerosis patients.

OBJECTIVES: To explore whether patients in an adherence trial who appeared not to take disease modifying therapy (DMT) for avoidance reasons could be reliably identified, by observational coding, for their main reason of not taking DMT. To determine whether reason groups could be distinguished by clinical and self-report psychological characteristics and intervention outcomes. METHOD: Participants were multiple sclerosis patients (N = 78, 88.5% female, mean age 45.64) demotivated to take DMT. Audio recordings of the sessions were coded for the main reason of not taking DMT. Reason groups were compared based on patient characteristics and intervention outcomes. RESULTS: Avoidance and three other reasons for not taking DMT (side effects, cost, and mild course) were reliably identified (κ = 0.88). Patient characteristics failed to distinguish participants in the Avoidance group, which also had poorer outcomes (X2 [2, n = 73] = 6.35, p = 0.036). CONCLUSIONS: Patients not taking DMT for avoidance reasons may need novel methods to identify them and encourage (re-)initiation.

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.

Baseline predictors of DMT reinitiation among patients with multiple sclerosis following an MI-CBT intervention.

Patients with multiple sclerosis (MS) are often nonadherent to their disease modifying therapy (DMT). While recent studies demonstrate enhanced DMT adherence following intervention grounded in motivational interviewing (MI), little is known about how to address DMT reinitiation among MS patients who have prematurely discontinued DMT against medical advice and do not intend to reinitiate. We examined baseline predictors of DMT reinitiation among patients with MS who discontinued medications against medical advice following a telephone-based MI and Cognitive Behavioral Therapy (MI-CBT) intervention. Following MI-CBT intervention, 66 patients reported whether or not they opted to reinitiate DMT. Rate of disease progression (ß = 0.295) and perceived personal control (ß = - 0.131) emerged as unique significant predictors of DMT reinitiation following intervention. Clinical characteristics and health-related beliefs may be used to prospectively identify patients most likely to reinitiate DMT following MI-CBT intervention, furthering the goal of preserving brain health and preventing neurologic decline in MS via appropriate DMT utilization. Further study is warranted to delineate potential mediators and moderators of DMT reinitiation outcomes.

Characterization of speech and language phenotype in children with NRXN1 deletions.

Neurexin 1 gene (NRXN1) deletions are associated with several neurodevelopmental disorders. Communication difficulties have been reported, yet no study has examined specific speech and language features of individuals with NRXN1 deletions. Here, we characterized speech and language phenotypes in 21 children (14 families), aged 1.8-17 years, with NRXN1 deletions. Deletions ranged from 74 to 702 kb and consisted mostly of either exons 1-3 or 1-5. Speech sound disorders were frequent (69%), although few were severe. The majority (57%) of children had difficulty with receptive and/or expressive language, although no homogeneous profiles of deficit were seen across semantic, morphological, or grammatical systems. Social language difficulties were seen in over half the sample (53%). All but two individuals with language difficulties also had intellectual disability/developmental delay. Overall, while speech and language difficulties were common, there was substantial heterogeneity in the severity and type of difficulties observed and no striking communication phenotype was seen. Rather, the speech and language deficits are likely part of broader concomitant neurodevelopmental profiles (e.g., intellectual disability, social skill deficits). Nevertheless, given the high rate of affectedness, it is important speech/language development is assessed so interventions can be applied during childhood in a targeted and timely manner.

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.

A Randomized Controlled Trial of an Outpatient Protocol for Transitioning Children from Tube to Oral Feeding: No Need for Amitriptyline.

OBJECTIVE: To assess the role of amitriptyline in the effectiveness of an outpatient protocol for weaning medically complicated children from tube to oral feeding. STUDY DESIGN: Twenty-one children seen in multidisciplinary outpatient feeding teams across 4 sites were recruited to a randomized placebo-controlled trial of a 6-month outpatient treatment protocol with behavioral, oral-motor, nutrition, and medication components. RESULTS: All of the children who completed the 6-month program (73%) were weaned to receive only oral feeding, regardless of group assignment. The transition from tube to oral feeding resulted in decreases in body mass index percentile and pain, some improvements in quality of life, and no statistically significant changes in cost. CONCLUSIONS: Amitriptyline is not a key component of this otherwise effective outpatient, interdisciplinary protocol for weaning children from tube to oral feeding. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01206478.

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.

A pilot study to improve adherence among MS patients who discontinue treatment against medical advice.

Between 30 and 50% of MS patients may prematurely discontinue disease modifying therapies. Little research has examined how to best talk with patients who have discontinued treatment against medical advice. The aim of this pilot study was to determine whether telephone counseling increases disease modifying therapy (DMT) re-initiation among nonadherent patients with multiple sclerosis (MS). Participants were eligible if they had relapsing-remitting disease, had stopped taking a DMT, and had no plan to re-initiate treatment despite a provider recommendation. Following a baseline assessment, 81 patients were randomly assigned to either five 20 min, weekly sessions of Motivational Interviewing/Cognitive Behavioral Therapy (MI-CBT) or Treatment as Usual (TAU) with brief education. At 10 weeks, patients initially assigned to TAU switched over to MI-CBT. Compared to patients in the TAU group, patients undergoing MI-CBT were significantly more likely to indicate they were re-initiating DMT (41.7 vs. 14.3%). These significant results were replicated among patients crossing over from TAU to MI-CBT. Treatment satisfaction was high, with 97% of participants reporting that they would recommend MI-CBT to other patients with MS. Results of this pilot study provide initial support for the use of MI-CBT among MS patients who have discontinued treatment against medical advice.Clinicaltrials.gov: NCT01925690.

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.