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

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

Reduced brain activation during spoken language processing in children with developmental language disorder and children with 22q11.2 deletion syndrome.

Language difficulties of children with Developmental Language Disorder (DLD) have been associated with multiple underlying factors and are still poorly understood. One way of investigating the mechanisms of DLD language problems is to compare language-related brain activation patterns of children with DLD to those of a population with similar language difficulties and a uniform etiology. Children with 22q11.2 deletion syndrome (22q11DS) constitute such a population. Here, we conducted an fMRI study, in which children (6-10yo) with DLD and 22q11DS listened to speech alternated with reversed speech. We compared language laterality and language-related brain activation levels with those of typically developing (TD) children who performed the same task. The data revealed no significant differences between groups in language lateralization, but task-related activation levels were lower in children with language impairment than in TD children in several nodes of the language network. We conclude that language impairment in children with DLD and in children with 22q11DS may involve (partially) overlapping cortical areas.

A Functional Magnetic Resonance Imaging Approach for Language Laterality Assessment in Young Children.

Functional magnetic resonance imaging (fMRI) is a usable technique to determine hemispheric dominance of language function, but high-quality fMRI images are difficult to acquire in young children. Here we aimed to develop and validate an fMRI approach to reliably determine hemispheric language dominance in young children. We designed two new tasks (story, SR; Letter picture matching, LPM) that aimed to match the interests and the levels of cognitive development of young children. We studied 32 healthy children (6-10 years old, median age 8.7 years) and seven children with epilepsy (7-11 years old, median age 8.6 years) and compared the lateralization index of the new tasks with those of a well-validated task (verb generation, VG) and with clinical measures of hemispheric language dominance. A conclusive assessment of hemispheric dominance (lateralization index ≤-0.2 or ≥0.2) was obtained for 94% of the healthy participants who performed both new tasks. At least one new task provided conclusive language laterality assessment in six out of seven participants with epilepsy. The new tasks may contribute to assessing language laterality in young and preliterate children and may benefit children who are scheduled for surgical treatment of disorders such as epilepsy.

Developmental differences in the brain response to unhealthy food cues: an fMRI study of children and adults.

BACKGROUND: Food cues are omnipresent and may trigger overconsumption. In the past 2 decades, the prevalence of childhood obesity has increased dramatically. Because children's brains are still developing, especially in areas important for inhibition, children may be more susceptible than adults to tempting food cues. OBJECTIVE: We examined potential developmental differences in children's and adults' responses to food cues to determine how these responses relate to weight status. DESIGN: We included 27 children aged 10-12 y and 32 adults aged 32-52 y. Functional magnetic resonance imaging data were acquired during a food-viewing task in which unhealthy and healthy food pictures were presented. RESULTS: Children had a stronger activation in the left precentral gyrus than did adults in response to unhealthy compared with healthy foods. In children, unhealthy foods elicited stronger activation in the right inferior temporal and middle occipital gyri, left precentral gyrus, bilateral opercular part of the inferior frontal gyrus, left hippocampus, and left middle frontal gyrus. Adults had stronger activation in the bilateral middle occipital gyrus and the right calcarine sulcus for unhealthy compared with healthy foods. Children with a higher body mass index (BMI) had lower activation in the bilateral dorsolateral prefrontal cortex while viewing unhealthy compared with healthy foods. In adults there was no correlation between BMI and neural response to unhealthy compared with healthy foods. CONCLUSIONS: Unhealthy foods might elicit more attention both in children and in adults. Children had stronger activation while viewing unhealthy compared with healthy foods in areas involved in reward, motivation, and memory. Furthermore, children activated a motivation and reward area located in the motor cortex more strongly than did adults in response to unhealthy foods. Finally, children with a higher BMI had less activation in inhibitory areas in response to unhealthy foods, which may mean they are more susceptible to tempting food cues. This trial was registered at www.trialregister.nl as NTR4255.

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

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

Supersize my brain: A cross-sectional voxel-based morphometry study on the association between self-reported dietary restraint and regional grey matter volumes.

Restrained eaters do not eat less than their unrestrained counterparts. Proposed underlying mechanisms are that restrained eaters are more reward sensitive and that they have worse inhibitory control. Although fMRI studies assessed these mechanisms, it is unknown how brain anatomy relates to dietary restraint. Voxel-based morphometry was performed on anatomical scans from 155 normal-weight females to investigate how regional grey matter volume correlates with restraint. A positive correlation was found in several areas, including the parahippocampal gyrus, hippocampus, striatum and the amygdala (bilaterally, p<0.05, corrected). A negative correlation was found in several areas, including the inferior frontal gyrus, superior frontal gyrus, supplementary motor area, middle cingulate cortex and precentral gyrus (p<0.05, corrected). That higher restraint relates to higher grey matter volume in reward-related areas and lower grey matter volume in regions involved in inhibition, provides a neuroanatomical underpinning of theories relating restraint to increased reward sensitivity and reduced inhibitory capacity.

Standardized food images: A photographing protocol and image database.

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

Functional MRI of Challenging Food Choices: Forced Choice between Equally Liked High- and Low-Calorie Foods in the Absence of Hunger.

We are continuously exposed to food and during the day we make many food choices. These choices play an important role in the regulation of food intake and thereby in weight management. Therefore, it is important to obtain more insight into the mechanisms that underlie these choices. While several food choice functional MRI (fMRI) studies have been conducted, the effect of energy content on neural responses during food choice has, to our knowledge, not been investigated before. Our objective was to examine brain responses during food choices between equally liked high- and low-calorie foods in the absence of hunger. During a 10-min fMRI scan 19 normal weight volunteers performed a forced-choice task. Food pairs were matched on individual liking but differed in perceived and actual caloric content (high-low). Food choice compared with non-food choice elicited stronger unilateral activation in the left insula, superior temporal sulcus, posterior cingulate gyrus and (pre)cuneus. This suggests that the food stimuli were more salient despite subject's low motivation to eat. The right superior temporal sulcus (STS) was the only region that exhibited greater activation for high versus low calorie food choices between foods matched on liking. Together with previous studies, this suggests that STS activation during food evaluation and choice may reflect the food's biological relevance independent of food preference. This novel finding warrants further research into the effects of hunger state and weight status on STS, which may provide a marker of biological relevance.

Sweet lies: neural, visual, and behavioral measures reveal a lack of self-control conflict during food choice in weight-concerned women.

Despite their intentions, weight-concerned individuals generally fail to control their eating behavior. However, it is unknown whether this failure is due to a lack of effortful self-control, or to not experiencing an internal conflict between weight goals and food temptations. The present study used fMRI, eye tracking and reaction times to assess the degree of conflict experienced by weight-concerned women during food choices that posed either a self-control dilemma (i.e., requiring a choice between healthy and palatable foods), or not. Contrary to the common assumption in self-control theory that food choices posing a self-control dilemma evoke internal conflict, we found that choices requiring self-control induced no conflict, as demonstrated by lower reaction times, fixation durations, number of gaze switches between snacks, and lower activation of the anterior cingulate cortex. Our results suggest that self-control failure might be due to a lack of experienced conflict, rather than to failing to act upon the perception of such conflict. This implies that effectiveness of weight maintenance interventions might be improved if they also focus on increasing the ability to detect a self-control dilemma, in addition to the current focus on increasing self-regulatory capacity.

Food-induced brain responses and eating behaviour.

The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques that could be used to address these. The brain responses associated with sensory stimulation (sight, olfaction and taste), gastric distension, gut hormone administration and food consumption are the subject of increasing investigation. Nevertheless, only few studies have examined relations between brain responses and eating behaviour. However, the neural circuits underlying eating behaviour are to a large extent generic, including reward, self-control, learning and decision-making circuitry. These limbic and prefrontal circuits interact with the hypothalamus, a key homeostatic area. Target areas for further elucidating the regulation of food intake are: (eating) habit and food preference formation and modification, the neural correlates of self-control, nutrient sensing and dietary learning, and the regulation of body adiposity. Moreover, to foster significant progress, data from multiple studies need to be integrated. This requires standardisation of (neuroimaging) measures, data sharing and the application and development of existing advanced analysis and modelling techniques to nutritional neuroscience data. In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.