Obesity and acute stress modulate appetite and neural responses in food word reactivity task.

Obesity can result from excess intake in response to environmental food cues, and stress can drive greater intake and body weight. We used a novel fMRI task to explore how obesity and stress influenced appetitive responses to relatively minimal food cues (words representing food items, presented similarly to a chalkboard menu). Twenty-nine adults (16F, 13M), 17 of whom had obesity and 12 of whom were lean, completed two fMRI scans, one following a combined social and physiological stressor and the other following a control task. A food word reactivity task assessed subjective food approach (wanting) as well as food avoidant (restraint) responses, along with neural responses, to words denoting high energy-density (ED) foods, low-ED foods, and non-foods. A multi-item ad-libitum meal followed each scan. The obese and lean groups demonstrated differences as well as similarities in activation of appetitive and attention/self-regulation systems in response to food vs. non-food, and to high-ED vs. low-ED food words. Patterns of activation were largely similar across stress and non-stress conditions, with some evidence for differences between conditions within both obese and lean groups. The obese group ate more than the lean group in both conditions. Our results suggest that neural responses to minimal food cues in stressed and non-stressed states may contribute to excess consumption and adiposity.

Patterns of body weight change affect weight loss during a multidisciplinary intervention in adolescents with obesity.

AIM: The current pediatric obesity health challenge necessitates a better understanding of the factors affecting weight loss success during interventions. The aim of this observational study was to test the impact of the rate of initial weight loss and body weight variability on weight loss during a 9-month residential, multidisciplinary weight loss program in adolescents with obesity. METHODS: This retrospective study considered a whole sample of 510 adolescents with obesity (12-16 years, 435 girls). Body weight assessment was performed before (T0) and each week during the 9 months of a multidisciplinary weight loss program. Initial weight change (week 4-W4) and overall weight change at week 12 (T1) and the end of the intervention (T2) were considered. Participants were divided into three groups (tertiles), based on their percentage of weight loss between T0 and W4; and weight variability was expressed by the root mean square error (RMSE) around each participant's regression line at each considered period (W4, T1, T2). RESULTS: Adolescents with lower initial weight loss at W4 (tertile 3) displayed the lesser weight loss at T1 and T2 compared with adolescents in tertile 1 and 2. The RMSE was positively associated with the percentage of weight loss of the period considered, but when the analyses were adjusted for age and initial body weight, there was no more significant association. CONCLUSIONS: The rate of weight loss during the first few weeks is crucial for weight loss success, and weight variability is positively associated with weight loss in adolescents with obesity. Overall, results show that initial body weight is a determinant characteristic to consider during a lifestyle intervention. Further studies are thus needed to better understand the relationship between body weight change patterns and weight loss during the dynamic state that is adolescence.

Greater within-person weight variability during infancy predicts future increases in z-BMI.

OBJECTIVE: This study tested the hypothesis that greater weight variability (WV; measured as root mean square error [RMSE]) during the first year of life predicts weight gain at year two and greater WV during the second year of life predicts greater weight gain at year three. METHODS: This was a prospective study using mother and offspring data from the Avon Longitudinal Study of Parents and Children. Infant z-BMI (BMI z score) and WV scores were calculated separately during years one and two. Maternal demographic, weight, and nursing-related measures were also used in analyses. RESULTS: Sample sizes in year-one and year-two analyses were 814 (448 male; 366 female) and 783 (432 male; 351 female), respectively. RMSE in year one significantly predicted z-BMI change in year two (ß [SE]: 0.32 [0.12]; p = 0.01; adjusted R2 = 0.07), controlling for z-BMI change in year one and z-BMI at birth. Similar significant prediction was found using year-two RMSE for year-three z-BMI (ß [SE]: 0.33 [0.14]; p = 0.02; adjusted R2 = 0.10). Maternal characteristics were not related to RMSE in year one or year two. CONCLUSIONS: Previous findings that WV predicts subsequent increases in body mass in adults were, for the first time, extended to infants.

Familial Obesity Risk and Current Excess Weight Influence Brain Structure in Adolescents.

OBJECTIVE: Obesity risk transmits from parents to children. Underlying neural mechanisms were investigated in this study by evaluating influences of familial obesity risk defined by maternal obesity and influences of current overweight on three indices of brain structure in adolescents. METHODS: In total, 22 lean adolescents with lean mothers (lean low-risk), 25 lean adolescents with mothers with obesity/overweight (lean high-risk), and 36 adolescents with obesity/overweight underwent structural MRI scans for estimation of regional gray and white matter volume and cortical thickness. RESULTS: The lean high-risk compared with the lean low-risk group demonstrated lower gray and white matter volume and cortical thickness in the postcentral gyrus (somatosensory cortex), lower gray and white matter volume in the opercular cortex (taste cortex), lower gray matter volume and cortical thickness in the anterior cingulate cortex, and lower cortical thickness in the precuneus. Comparisons of the lean and obesity/overweight groups revealed further structural alterations in the postcentral gyrus, posterior cingulate gyrus, and middle temporal gyrus. CONCLUSIONS: Familial obesity risk and current obesity/overweight were associated with overlapping and distinct patterns of brain structure alterations. Longitudinal studies are warranted to investigate whether structural changes associated with familial obesity risk predict future weight trajectories.

Individual differences in within-subject weight variability: There's a signal in the noise.

Humans show a high degree of stability in their body weights over time, a phenomenon explained by powerful, redundant homeostatic mechanisms. Nonetheless, human populations are also highly susceptible to develop epidemic levels of overweight in an obesogenic environment. Relatively little is known about the process responsible for the transition from remarkable weight stability to relentless weight gain. We have been studying individual differences in within-subject variability in body weights to learn more about this transition. This research has revealed that those who show greater WV over time are more susceptible to future weight gain; greater WV in those losing weight also predicts poorer weight loss maintenance. All the above findings continue to hold when baseline BMI and weight change over the WV assessment period are controlled. The relation of these newer findings to several trends in existing research was considered; these include the relation of weight cycling and morbidity, WV and eating/affective dysregulation, WV and medical diseases and WV and variability in daily energy intake. It appears that elevated WV per se is a risk factor for unfavorable clinical outcomes but little is known about the mechanisms accounting for these associations.

Weight variability during self-monitored weight loss predicts future weight loss outcome.

BACKGROUND: Obesity treatments often do not produce long-term results. It is therefore critical to better understand biological and behavioral correlates or predictors of future weight change. OBJECTIVE: We tested the hypothesis that greater weight variability, independent of total body weight change, during early weight loss would predict degree of long-term success. SUBJECTS/METHODS: We included 24,009 American users of the Withings smart scale with over a year's worth of self-monitored weight data. Multilevel modeling was used to calculate weight variability as the root mean square error around participants' weight trajectory regression line, using weekly average weights from the first 12 weeks of weight loss. Linear regressions were then used to examine whether weight variability predicted weight change from week 12 to week 48, 72, and 96. RESULTS: Greater weight variability predicted less weight loss/more weight regain at week 48 (b ± SE: 1.18 ± 0.17, p < 0.001), week 72 (b ± SE: 1.45 ± 0.21, p < 0.001), and week 96 (b ± SE: 1.45 ± 0.23, p < 0.001), controlling for baseline BMI and overall weight change during the first 12 weeks. An interaction effect was found between weight variability and baseline BMI such that the relationship between weight variability and later weight change was stronger in individuals with lower baseline BMI. CONCLUSIONS: This study found that in a large population sample, weight variability early on during weight loss significantly predicted longer term weight loss outcomes. The results provide further support that weight variability be considered an important predictor of future weight change. Research is needed to understand the mechanisms underlying this effect.

Weight Suppression in Eating Disorders: a Research and Conceptual Update.

PURPOSE OF REVIEW: Weight suppression, the discrepancy between an individual's highest past weight at adult height and his or her current weight, is related to many characteristics of individuals with eating disorders. This paper reviews research findings from the past 5 years, draws several implications regarding the mechanism underlying these effects, and proposes new approaches to measuring weight suppression. RECENT FINDINGS: Studies were reviewed under the categories of anorexia nervosa, bulimia nervosa, and mixed or miscellaneous samples, with more studies falling into the last category than in the first two. Recent findings have continued to show that weight suppression is related to a wide variety of biological and behavioral features in both diagnosed and sub-clinical samples. Weight suppression promotes weight gain which is anathema to individuals with eating disorders, putting them in a biobehavioral bind that appears to prolong their disorder. Priorities for future research are to understand the mechanisms underlying the effects of weight suppression, evaluate new ways of defining weight suppression, and study its implications for modifying treatment.

Neural correlates of familial obesity risk and overweight in adolescence.

BACKGROUND: Rates of adolescent obesity and overweight are high. The offspring of overweight parents are at increased risk of becoming obese later in life. Investigating neural correlates of familial obesity risk and current overweight status in adolescence could help identify biomarkers that predict future obesity and that may serve as novel targets for obesity interventions. OBJECTIVE: Our primary aim was to use functional MRI to compare neural responses to words denoting high or low energy density (ED) foods and non-foods, in currently lean adolescents at higher compared with lower familial risk for obesity, and in overweight compared with lean adolescents. Secondary aims were to assess group differences in subjective appetite when viewing food and non-food words, and in objective ad libitum intake of high-ED foods in a laboratory setting. DESIGN: We recruited 36 adolescents (14-19y), of whom 10 were (obese/overweight "overweight"), 16 lean with obese/overweight mothers (lean high-risk, "lean-HR"), and 10 lean with lean mothers (lean low-risk, "lean-LR"). All underwent fMRI scanning while they viewed words representing high-ED foods, low-ED foods, or non-foods, and provided appetitive ratings in response to each word stimulus. They then consumed a multi-item ad libitum buffet meal. RESULTS: Food compared with non-food words activated a distributed emotion/reward system including insula and pregenual anterior cingulate cortex (ACC). Participants who were at increasing risk for obesity exhibited progressively weaker activation of an attentional/regulatory system including dorsolateral prefrontal cortex (PFC), dorsal ACC, and basal ganglia nuclei (activation was greatest in lean-LR, intermediate in lean-HR, and weakest in the overweight group). These group differences were most apparent for neural responses to high-compared with low-ED foods. Lean-HR (compared with lean-LR and overweight) adolescents reported greater desire for high-ED foods. Meal intake was greatest for the overweight, then lean-HR, then lean-LR groups. CONCLUSIONS: Adolescents at higher obesity risk exhibited reduced neural responses to high-ED food cues in a neural system that subserves attention and self-regulation. They also reported heightened appetitive responses to high-ED cues. Interventions that promote the capacity for self-regulation could prevent youth who have a familial predisposition for obesity from translating risk into reality.

Behind binge eating: A review of food-specific adaptations of neurocognitive and neuroimaging tasks.

Recurrent binge eating, or overeating accompanied by a sense of loss of control, is a major public health concern. Identifying similarities and differences among individuals with binge eating and those with other psychiatric symptoms and characterizing the deficits that uniquely predispose individuals to eating problems are essential to improving treatment. Research suggests that altered reward and control-related processes may contribute to dysregulated eating and other impulsive behaviors in binge-eating populations, but the best methods for reliably assessing the contributions of these processes to binge eating are unclear. In this review, we summarize standard neurocognitive and neuroimaging tasks that assess reward and control-related processes, describe adaptations of these tasks used to study eating and food-specific responsivity and deficits, and consider the advantages and limitations of these tasks. Future studies integrating both general and food-specific tasks with neuroimaging will improve understanding of the neurocognitive processes and neural circuits that contribute to binge eating and could inform novel interventions that more directly target or prevent this transdiagnostic behavior.

Greater anterior cingulate activation and connectivity in response to visual and auditory high-calorie food cues in binge eating: Preliminary findings.

Obese individuals show altered neural responses to high-calorie food cues. Individuals with binge eating [BE], who exhibit heightened impulsivity and emotionality, may show a related but distinct pattern of irregular neural responses. However, few neuroimaging studies have compared BE and non-BE groups. To examine neural responses to food cues in BE, 10 women with BE and 10 women without BE (non-BE) who were matched for obesity (5 obese and 5 lean in each group) underwent fMRI scanning during presentation of visual (picture) and auditory (spoken word) cues representing high energy density (ED) foods, low-ED foods, and non-foods. We then compared regional brain activation in BE vs. non-BE groups for high-ED vs. low-ED foods. To explore differences in functional connectivity, we also compared psychophysiologic interactions [PPI] with dorsal anterior cingulate cortex [dACC] for BE vs. non-BE groups. Region of interest (ROI) analyses revealed that the BE group showed more activation than the non-BE group in the dACC, with no activation differences in the striatum or orbitofrontal cortex [OFC]. Exploratory PPI analyses revealed a trend towards greater functional connectivity with dACC in the insula, cerebellum, and supramarginal gyrus in the BE vs. non-BE group. Our results suggest that women with BE show hyper-responsivity in the dACC as well as increased coupling with other brain regions when presented with high-ED cues. These differences are independent of body weight, and appear to be associated with the BE phenotype.

Overlapping neurobehavioral circuits in ADHD, obesity, and binge eating: evidence from neuroimaging research.

Attention-deficit/hyperactivity disorder (ADHD) and conditions involving excessive eating (eg, obesity, binge/loss of control eating) are increasingly prevalent within pediatric populations, and correlational and some longitudinal studies have suggested inter-relationships between these disorders. In addition, a number of common neural correlates are emerging across conditions, eg, functional abnormalities within circuits subserving reward processing and executive functioning. To explore this potential cross-condition overlap in neurobehavioral underpinnings, we selectively review relevant functional neuroimaging literature, specifically focusing on studies probing (i) reward processing, (ii) response inhibition, and (iii) emotional processing and regulation, and we outline 3 specific shared neurobehavioral circuits. Based on our review, we also identify gaps within the literature that would benefit from further research.

Amodal brain activation and functional connectivity in response to high-energy-density food cues in obesity.

OBJECTIVE: The obesogenic environment is pervasive, yet only some people become obese. The aim was to investigate whether obese individuals show differential neural responses to visual and auditory food cues, independent of cue modality. METHODS: Obese (BMI 29-41, n = 10) and lean (BMI 20-24, n = 10) females underwent fMRI scanning during presentation of auditory (spoken word) and visual (photograph) cues representing high-energy-density (ED) and low-ED foods. The effect of obesity on whole-brain activation, and on functional connectivity with the midbrain/VTA, was examined. RESULTS: Obese compared with lean women showed greater modality-independent activation of the midbrain/VTA and putamen in response to high-ED (vs. low-ED) cues, as well as relatively greater functional connectivity between the midbrain/VTA and cerebellum (P < 0.05 corrected). CONCLUSIONS: Heightened modality-independent responses to food cues within the midbrain/VTA and putamen, and altered functional connectivity between the midbrain/VTA and cerebellum, could contribute to excessive food intake in obese individuals.

Parent feeding behavior and child appetite: associations depend on feeding style.

OBJECTIVE: Eating behavior traits measured in early life predict eating behavior and weight trajectories later in development, and may be associated with certain parental feeding behaviors. Our goal was to investigate the relationship between a range of feeding behaviors, and preschoolers' appetitive traits. METHOD: Four hundred thirty-nine parents of UK 3-5 year olds completed scales measuring authoritarian vs. authoritative forms of limiting (Restriction vs. Monitoring) and promoting (Pressuring vs. Prompting) intake, as well as Emotional and Instrumental Feeding. Parents also completed scales measuring child Food responsiveness and Satiety responsiveness. Child BMI z-scores were calculated based on measured heights and weights. RESULTS: Parental Restriction was significantly associated with greater child Food responsiveness (p < .001), but parental Monitoring was not. Parental Pressuring was significantly associated with greater child Satiety responsiveness (p < .001), while parental Prompting was not. Parental Instrumental and Emotional feeding were both associated with greater child Food responsiveness (p < .001). All relationships were independent of child BMI z-score. DISCUSSION: Prospective data are needed to determine whether the parent-child feeding relationships identified here promote, or protect against, the development of eating pathology in children. However, our results suggest that cross-sectional associations depend on the style (e.g., authoritarian vs. authoritative), as well as the type of feeding behavior measured.

Appetitive traits from infancy to adolescence: using behavioral and neural measures to investigate obesity risk.

We come into the world with enduring predispositions towards food, which interact with environmental factors to influence our eating behaviors and weight trajectories. But our fates are not sealed - by learning more about this process we can identify ways to intervene. To advance this goal this we need to be able to assess appetitive traits such as food cue responsiveness and satiety sensitivity at different developmental stages. Assessment methods might include behavioral measures (e.g. eating behavior tests, psychometric questionnaires), but also biomarkers such as brain responses to food cues measured using fMRI. Evidence from infants, children and adolescents suggests that these indices of appetite differ not only with body weight, but also with familial obesity risk as assessed by parent weight, which reflects both genetic and environmental influences, and may provide a useful predictor of obesity development. Behavioral and neural approaches have great potential to inform each other: examining eating behavior can help us identify meaningful appetitive endophenotypes whose neural bases can be probed, while increasing knowledge of the shared neurobiology underlying appetite, obesity, and related behaviors and disorders may ultimately lead to innovative generalized interventions. Another challenge will be to combine comprehensive behavioral and neural assessments of appetitive traits with measures of relevant genetic and environmental factors within long-term prospective studies. This approach may help to identify the biobehavioral precursors of obesity, and lay the foundations for targeted neurobehavioral interventions that can interrupt the pathway to excess weight.

Cortical control of adaptive locomotion in wild-type mice and mutant mice lacking the ephrin-Eph effector protein alpha2-chimaerin.

In voluntary control, supraspinal motor systems select the appropriate response and plan movement mechanics to match task constraints. Spinal circuits translate supraspinal drive into action. We studied the interplay between motor cortex (M1) and spinal circuits during voluntary movements in wild-type (WT) mice and mice lacking the α2-chimaerin gene (Chn1(-/-)), necessary for ephrinB3-EphA4 signaling. Chn1(-/-) mice have aberrant bilateral corticospinal systems, aberrant bilateral-projecting spinal interneurons, and disordered voluntary control because they express a hopping gait, which may be akin to mirror movements. We addressed three issues. First, we determined the role of the corticospinal system in adaptive control. We trained mice to step over obstacles during treadmill locomotion. We compared performance before and after bilateral M1 ablation. WT mice adaptively modified their trajectory to step over obstacles, and M1 ablation increased substantially the incidence of errant steps over the obstacle. Chn1(-/-) mice randomly stepped or hopped during unobstructed locomotion but hopped over the obstacle. Bilateral M1 ablation eliminated this obstacle-dependent hop selection and increased forelimb obstacle contact errors. Second, we characterized the laterality of corticospinal action in Chn1(-/-) mice using pseudorabies virus retrograde transneuronal transport and intracortical microstimulation. We showed bilateral connections between M1 and forelimb muscles in Chn1(-/-) and unilateral connections in WT mice. Third, in Chn1(-/-) mice, we studied adaptive responses before and after unilateral M1 ablation. We identified a more important role for contralateral than ipsilateral M1 in hopping over the obstacle. Our findings suggest an important role for M1 in the mouse in moment-to-moment adaptive control, and further, using Chn1(-/-) mice, a role in mediating task-dependent selection of mirror-like hopping movements over the obstacle. Our findings also stress the importance of subcortical control during adaptive locomotion because key features of the trajectory remained largely intact after M1 ablation.