Interactions between emotions and eating behaviors: Main issues, neuroimaging contributions, and innovative preventive or corrective strategies.

Emotional eating is commonly defined as the tendency to (over)eat in response to emotion. Insofar as it involves the (over)consumption of high-calorie palatable foods, emotional eating is a maladaptive behavior that can lead to eating disorders, and ultimately to metabolic disorders and obesity. Emotional eating is associated with eating disorder subtypes and with abnormalities in emotion processing at a behavioral level. However, not enough is known about the neural pathways involved in both emotion processing and food intake. In this review, we provide an overview of recent neuroimaging studies, highlighting the brain correlates between emotions and eating behavior that may be involved in emotional eating. Interaction between neural and neuro-endocrine pathways (HPA axis) may be involved. In addition to behavioral interventions, there is a need for a holistic approach encompassing both neural and physiological levels to prevent emotional eating. Based on recent imaging, this review indicates that more attention should be paid to prefrontal areas, the insular and orbitofrontal cortices, and reward pathways, in addition to regions that play a major role in both the cognitive control of emotions and eating behavior. Identifying these brain regions could allow for neuromodulation interventions, including neurofeedback training, which deserves further investigation.

Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

This study explores the long-term effects of exposure to a maternal Western diet (WD) vs. standard diet (SD) in the Yucatan minipig, on the adult progeny at lean status ( n = 32), and then overweight status. We investigated eating behavior, cognitive abilities, brain basal glucose metabolism, dopamine transporter availability, microbiota activity, blood lipids, and glucose tolerance. Although both groups demonstrated similar cognitive abilities in a holeboard test, WD pigs expressed a higher stress level than did SD pigs (immobility, P < 0.05) and lower performance in an alley maze ( P = 0.06). WD pigs demonstrated lower dopamine transporter binding potential in the hippocampus and parahippocampal cortex ( P < 0.05 for both), as well as a trend in putamen ( P = 0.07), associated with lower basal brain activity in the prefrontal cortex and nucleus accumbens ( P < 0.05) compared with lean SD pigs. Lean WD pigs demonstrated a lower glucose tolerance than did SD animals (higher glucose peak, P < 0.05) and a tendency to a higher incremental area under the curve of insulin from 0 to 30 minutes after intravenous glucose injection ( P < 0.1). Both groups developed glucose intolerance with overweight, but WD animals were less impacted than SD animals. These results demonstrate that maternal diet shaped the offspring's brain functions and cognitive responses long term, even after being fed a balanced diet from weaning, but behavioral effects were only revealed in WD pigs under anxiogenic situation; however, WD animals seemed to cope better with the obesogenic diet from a metabolic standpoint.-Gautier, Y., Luneau, I., Coquery, N., Meurice, P., Malbert, C.-H., Guerin, S., Kemp, B., Bolhuis, J. E., Clouard, C., Le Huërou-Luron, I., Blat, S., Val-Laillet, D. Maternal Western diet during gestation and lactation modifies adult offspring's cognitive and hedonic brain processes, behavior, and metabolism in Yucatan minipigs.

Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Butyrate can improve gut functions, whereas histone deacetylase inhibitors might alleviate neurocognitive alterations. Our aim was to assess whether oral butyrate could modulate brain metabolism and plasticity and if this would relate to gut function. Sixteen pigs were subjected to sodium butyrate (SB) supplementation via beverage water or water only [control (C)]. All pigs had blood sampled after 2 and 3 wk of treatment, and were subjected to a brain positron emission tomography after 3 wk. Animals were euthanized after 4 wk to sample pancreas, intestine, and brain for gut physiology and anatomy measurements, as well as hippocampal histology, Ki67, and doublecortin (DCX) immunohistochemistry. SB compared with C treatment triggered basal brain glucose metabolism changes in the nucleus accumbens and hippocampus ( P = 0.003), increased hippocampal granular cell layer volume ( P = 0.006), and neurogenesis (Ki67: P = 0.026; DCX: P = 0.029). After 2 wk of treatment, plasma levels of glucose, insulin, lactate, glucagon-like peptide 1, and peptide tyrosine tyrosine remained unchanged. After 3 wk, plasma levels of lactate were lower in SB compared with C animals ( P = 0.028), with no difference for glucose and insulin. Butyrate intake impacted very little gut anatomy and function. These results demonstrate that oral SB impacted brain functions with little effects on the gut.-Val-Laillet, D., Guérin, S., Coquery, N., Nogret, I., Formal, M., Romé, V., Le Normand, L., Meurice, P., Randuineau, G., Guilloteau, P., Malbert, C.-H., Parnet, P., Lallès, J.-P., Segain, J.-P. Oral sodium butyrate impacts brain metabolism and hippocampal neurogenesis, with limited effects on gut anatomy and function in pigs.

Cluster versus ROI analysis to assess combined antiangiogenic therapy and radiotherapy in the F98 rat-glioma model.

For glioblastoma (GBM), current therapeutic approaches focus on the combination of several therapies, each of them individually approved for GBM or other tumor types. Many efforts are made to decipher the best sequence of treatments that would ultimately promote the most efficient tumor response. There is therefore a strong interest in developing new clinical in vivo imaging procedures that can rapidly detect treatment efficacy and allow individual modulation of the treatment. In this preclinical study, we propose to evaluate tumor tissue changes under combined therapies, tumor vascular normalization under antiangiogenic treatment followed by radiotherapy, using a voxel-based clustering approach. This approach was applied to a rat model of glioma (F98). Six MRI parameters were mapped: apparent diffusion coefficient, vessel wall permeability, cerebral blood volume fraction, cerebral blood flow, tissue oxygen saturation and vessel size index. We compared the classical region of interest (ROI)-based analysis with a cluster-based analysis. Five clusters, defined by their MRI features, were sufficient to characterize tumor progression and tumor changes during treatments. These results suggest that the cluster-based analysis was as efficient as the ROI-based analysis to assess tumor physiological changes during treatment, but also gave additional information regarding the voxels impacted by treatments and their localization within the tumor. Overall, cluster-based analysis appears to be a powerful tool for subtle monitoring of tumor changes during combined therapies.

A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

A suboptimal early nutritional environment (i.e., excess of energy, sugar, and fat intake) can increase susceptibility to diseases and neurocognitive disorders. The purpose of this study was to investigate in nonobese Yucatan minipigs (Sus scrofa) the impact of maternal diet [standard diet (SD) vs. Western diet (WD)] during gestation and 25 d of lactation on milk composition, blood metabolism, and microbiota activity of sows (n = 17) and their piglets (n = 65), and on spatial cognition (n = 51), hippocampal plasticity (n = 17), and food preferences/motivation (n = 51) in the progeny. Milk dry matter and lipid content, as well as plasma total cholesterol and free fatty acid (FFA) concentrations (P < 0.05) were higher in WD than in SD sows. Microbiota activity decreased in both WD sows and 100-d-old piglets (P < 0.05 or P < 0.10, depending on short-chain FAs [SCFAs]). At weaning [postnatal day (PND) 25], WD piglets had increased blood triglyceride and FFA levels (P < 0.01). Both SD and WD piglets consumed more of a known SD than an unknown high-fat and -sucrose (HFS) diet (P < 0.0001), but were quicker to obtain HFS rewards compared with SD rewards (P < 0.01). WD piglets had higher working memory (P = 0.015) and reference memory (P < 0.001) scores, which may reflect better cognitive abilities in the task context and a higher motivation for the food rewards. WD piglets had a smaller hippocampal granular cell layer (P = 0.03) and decreased neurogenesis (P < 0.005), but increased cell proliferation (P < 0.001). A maternal WD during gestation and lactation, even in the absence of obesity, has significant consequences for piglets' blood lipid levels, microbiota activity, gut-brain axis, and neurocognitive abilities after weaning.-Val-Laillet, D., Besson, M., Guérin, S., Coquery, N., Randuineau, G., Kanzari, A., Quesnel, H., Bonhomme, N., Bolhuis, J. E., Kemp, B., Blat, S., Le Huërou-Luron, I., Clouard, C. A maternal Western diet during gestation and lactation modifies offspring's microbiota activity, blood lipid levels, cognitive responses, and hippocampal neurogenesis in Yucatan pigs.

Emotional overeating is common and negatively associated with alcohol use in normal-weight female university students.

INTRODUCTION: Eating in response to specific emotional cues was hitherto investigated in relation to weight gain, eating disorders, and psychiatric and addictive disorders. Given the difficulties in treating established obesity, preventive interventions towards normal-weight subjects could be more appropriate and cost effective. In order to design such interventions, it is important to characterize emotional overeating in normal-weight subjects, especially young women. METHODS: Female university students aged 18-24 years with healthy Body Mass Index (comprised between 18.5 and 24.9) were asked to complete questionnaires while attending a medical consultation. Emotional Eating frequency in the last 28 days was assessed together with data on habitual physical activity, drinking patterns, substance abuse, suspected eating disorders and cognitive/behavioural components of eating. Sociodemographic data and tobacco use were also collected. RESULTS: Half of participants reported intermittent Emotional Overeating in the last 28 days, mostly during one to five days in the last 28 days, in response to Anxiety (51.3%), Loneliness (45.1%), Sadness (44.8%), and Happiness (43.6%), and to a lesser extent in response to Tiredness (27.4%) and Anger (14.6%). In multivariate analysis, Distress-Induced Overeating (DIO) correlated positively with inability to resist emotional cues, disordered eating symptoms, and loss of control over food intake. It correlated negatively with moderate and excessive drinking. CONCLUSION: A large proportion of normal-weight female students used intermittent overeating episodes as a time-limited response to emotional states, especially anxiety. DIO was negatively correlated with alcohol use, which suggests two distinct and somewhat exclusive ways of coping with negative emotions. It was higher in the minority of students with disordered eating symptoms and loss of control over food intake, highlighting the need for a systematic screening in all female students entering college.

Subjective feeling of control during fNIRS-based neurofeedback targeting the DL-PFC is related to neural activation determined with short-channel correction.

Neurofeedback (NF) training is a promising preventive and therapeutic approach for brain and behavioral impairments, the dorsolateral prefrontal cortex (DL-PFC) being a relevant region of interest. Functional near-infrared spectroscopy (NIRS) has recently been applied in NF training. However, this approach is highly sensitive to extra-cerebral vascularization, which could bias measurements of cortical activity. Here, we examined the feasibility of a NF training targeting the DL-PFC and its specificity by assessing the impact of physiological confounds on NF success via short-channel offline correction under different signal filtering conditions. We also explored whether the individual mental strategies affect the NF success. Thirty volunteers participated in a single 15-trial NF session in which they had to increase the oxy-hemoglobin (HbO2) level of their bilateral DL-PFC. We found that 0.01-0.09 Hz band-pass filtering was more suited than the 0.01-0.2 Hz band-pass filter to highlight brain activation restricted to the NF channels in the DL-PFC. Retaining the 10 out of 15 best trials, we found that 18 participants (60%) managed to control their DL-PFC. This number dropped to 13 (43%) with short-channel correction. Half of the participants reported a positive subjective feeling of control, and the "cheering" strategy appeared to be more effective in men (p<0.05). Our results showed successful DL-PFC fNIRS-NF in a single session and highlighted the value of accounting for extra cortical signals, which can profoundly affect the success and specificity of NF training.

Emotional overeating affected nine in ten female students during the COVID-19 university closure: A cross-sectional study in France.

OBJECTIVES: To estimate the proportion of female university students reporting overeating (EO) in response to emotions during the COVID-19 university closures, and to investigate social and psychological factors associated with this response to stress. DESIGN: Online survey gathered sociodemographic data, alcohol/drugs use disorders, boredom proneness and impulsivity using validated questionnaires, and EO using the Emotional Overeating Questionnaire (EOQ) assessing eating in response to six emotions (anxiety, sadness, loneliness, anger, fatigue, happiness), whose structure remains to be determined. PARTICIPANTS: Sample of 302 female students from Rennes University, France. MAIN OUTCOME MEASURE: Frequencies of emotional overeating. ANALYSIS: The frequency of emotional overeating was expressed for each emotion as percentages. Exploratory Factor analyses (EFA) were used to determine EOQ structure and provide an index of all EOQ items used for further analysis. Linear regression models were used to explore relationships between EO and others covariates. RESULTS: Nine in ten participants reported intermittent EO in the last 28 days, mostly during 6 to 12 days, in response to Anxiety (75.5%), Sadness (64.5%), Happiness (59.9%), Loneliness (57.9%), Tiredness (51.7%), and to a lesser extent to Anger (31.1%). EFA evidenced a one-factor latent variable reflecting "Distress-Induced Overeating" positively correlated with internal boredom proneness, tobacco use, attentional impulsivity, inability to resist emotional cues, and loss of control over food intake, and negatively with age and well-being. EO was unrelated to body mass index or substance abuse. CONCLUSION AND IMPLICATIONS: Nine in ten female students reported emotional overeating during the COVID-19 university closure. This response to stress was related to eating tendencies typical of young women, but also to personality/behavioral patterns such as boredom and impulsivity proneness. Better understanding of the mechanisms underlying EO in response to stress and lack of external/social stimulation would improve preventive interventions.

Exposure to a sensory functional ingredient in the pig model modulates the blood-oxygen-level dependent brain responses to food odor and acute stress during pharmacological MRI in the frontostriatal and limbic circuits.

Introduction: In the present study, we examined the effects of a supplementation with a sensory functional ingredient (FI, D16729, Phodé, France) containing vanillin, furaneol, diacetyl and a mixture of aromatic fatty acids on the behavioural and brain responses of juvenile pigs to acute stress. Methods: Twenty-four pigs were fed from weaning with a standard granulated feed supplemented with the functional ingredient D16729 (FS animals, N = 12) or a control formulation (CT animals, N = 12). After a feed transition (10 days after weaning), the effects of FI were investigated on eating behaviour during two-choice feed preference tests. Emotional reactivity to acute stress was then investigated during openfield (OF), novel suddenly moving object (NSO), and contention tests. Brain responses to the FI and the two different feeds' odour, as well as to an acute pharmacological stressor (injection of Synacthen®) were finally investigated with functional magnetic resonance imaging (fMRI). Results: FS animals tended to spend more time above the functional feed (p = 0.06) and spent significantly more time at the periphery of the arena during NSO (p < 0.05). Their latency to contact the novel object was longer and they spent less time exploring the object compared to CT animals (p < 0.05 for both). Frontostriatal and limbic responses to the FI were influenced by previous exposure to FI, with higher activation in FS animals exposed to the FI feed odor compared to CT animals exposed to a similarly familiar feed odor without FI. The pharmacological acute stress provoked significant brain activations in the prefrontal and thalamic areas, which were alleviated in FS animals that also showed more activity in the nucleus accumbens. Finally, the acute exposure to FI in naive animals modulated their brain responses to acute pharmacological stress. Discussion: Overall, these results showed how previous habituation to the FI can modulate the brain areas involved in food pleasure and motivation while alleviating the brain responses to acute stress.

Exploration of fMRI brain responses to oral sucrose after Roux-en-Y gastric bypass in obese yucatan minipigs in relationship with microbiota and metabolomics profiles.

BACKGROUND & AIMS: In most cases, Roux-en-Y gastric bypass (RYGBP) is an efficient intervention to lose weight, change eating behavior and improve metabolic outcomes in obese patients. We hypothesized that weight loss induced by RYGBP in obese Yucatan minipigs would induce specific modifications of the gut-brain axis and neurocognitive responses to oral sucrose stimulation in relationship with food intake control. METHODS: An integrative study was performed after SHAM (n = 8) or RYGBP (n = 8) surgery to disentangle the physiological, metabolic and neurocognitive mechanisms of RYGBP. BOLD fMRI responses to sucrose stimulations at different concentrations, brain mRNA expression, cecal microbiota, and plasma metabolomics were explored 4 months after surgery and integrated with WGCNA analysis. RESULTS: We showed that weight loss induced by RYGBP or SHAM modulated differently the frontostriatal responses to oral sucrose stimulation, suggesting a different hedonic treatment and inhibitory control related to palatable food after RYGBP. The expression of brain genes involved in the serotoninergic and cannabinoid systems were impacted by RYGBP. Cecal microbiota was deeply modified and many metabolite features were differentially increased in RYGBP. Data integration with WGCNA identified interactions between key drivers of OTUs and metabolites features linked to RYGBP. CONCLUSION: This longitudinal study in the obese minipig model illustrates with a systemic and integrative analysis the mid-term consequences of RYGBP on brain mRNA expression, cecal microbiota and plasma metabolites. We confirmed the impact of RYGBP on functional brain responses related to food reward, hedonic evaluation and inhibitory control, which are key factors for the success of anti-obesity therapy and weight loss maintenance.

Intrahippocampal transplantation of mesenchymal stromal cells promotes neuroplasticity.

BACKGROUND AIMS: Multipotent mesenchymal stromal cells (MSC) secrete soluble factors that stimulate the surrounding microenvironment. Such paracrine effects might underlie the potential benefits of many stem cell therapies. We tested the hypothesis that MSC are able to enhance intrinsic cellular plasticity in the adult rat hippocampus. METHODS: Rat bone marrow-derived MSC were labeled with very small superparamagnetic iron oxide particles (VSOP), which allowed for non-invasive graft localization by magnetic resonance imaging (MRI). Moreover, MSC were transduced with lentiviral vectors to express the green fluorescent protein (GFP). The effects of bilateral MSC transplantation on hippocampal cellular plasticity were assessed using the thymidine analogs 5-bromo-2'-deoxyuridine (BrdU) and 5-iodo-2'-deoxyuridine (IdU). Behavioral testing was performed to examine the consequences of intrahippocampal MSC transplantation on locomotion, learning and memory, and anxiety-like and depression-like behavior. RESULTS: We found that intrahippocampal transplantation of MSC resulted in enhanced neurogenesis despite short-term graft survival. In contrast, systemic administration of the selective serotonin re-uptake inhibitor citalopram increased cell survival but did not affect cell proliferation. Intrahippocampal transplantation of MSC did not impair behavioral functions in rats, but only citalopram exerted anti-depressant effects. CONCLUSIONS: This is the first study to examine the effects of intrahippocampal transplantation of allogeneic MSC on hippocampal structural plasticity and behavioral functions in rats combined with non-invasive cell tracking by MRI. We found that iron oxide nanoparticles can be used to detect transplanted MSC in the brain. Although graft survival was short, intrahippocampal transplantation of MSC resulted in long-term changes in hippocampal plasticity. Our results suggest that MSC can be used to stimulate adult neurogenesis.

Acute Effects of Different Electroacupuncture Point Combinations to Modulate the Gut-Brain Axis in the Minipig Model.

This study aimed to compare the gut-brain axis responses to acute electroacupuncture (EA) at different acupoint combinations in the minipig model. Four adult Yucatan minipigs were subjected twice to four acute EA treatments (25-minute acute sessions) including sham (false acupoints) and control (no EA), during anesthesia and according to a Latin-square design paradigm. Acupoint combinations (4 loci each) are head-abdomen (#70 Dafengmen, #35 Sanwan), back (bilateral #27 Pishu, #28 Weishu), leg (bilateral #79 Hangou, #63 Housanli), and sham (2 bilateral points that are not acupoints). Electrocardiograms were performed to explore heart rate variability (HRV). Infrared thermography was used to measure skin temperature at the stimulation points. Saliva (cortisol) and blood samples (leptin, total/active ghrelin, insulin, and glucose) were collected for further analyses before and after acute EA. All animals were also subjected to BOLD fMRI to investigate the brain responses to EA. Acute EA significantly modulated several physiological and metabolic parameters compared to basal, sham, and/or control conditions, with contrasting effects in terms of BOLD responses in brain regions involved in the hedonic and cognitive control of food intake. The head-abdomen combination appeared to be the most promising combination in terms of brain modulation of the corticostriatal circuit, with upregulation of the dorsolateral prefrontal cortex, dorsal striatum, and anterior cingulate cortex. It also induced significantly lower plasma ghrelin levels compared to sham, suggesting anorectic effects, as well as no temperature drop at the stimulation site. This study opens the way to a further preclinical trial aimed at investigating chronic EA in obese minipigs.

Brain Responses to Food Choices and Decisions Depend on Individual Hedonic Profiles and Eating Habits in Healthy Young Women.

The way different food consumption habits in healthy normal-weight individuals can shape their emotional and cognitive relationship with food and further disease susceptibility has been poorly investigated. Documenting the individual consumption of Western-type foods (i.e., high-calorie, sweet, fatty, and/or salty) in relation to psychological traits and brain responses to food-related situations can shed light on the early neurocognitive susceptibility to further diseases and disorders. We aimed to explore the relationship between eating habits, psychological components of eating, and brain responses as measured by blood oxygen level-dependent functional magnetic resonance imaging (fMRI) during a cognitive food choice task and using functional connectivity (FC) during resting-state fMRI (rsfMRI) in a population of 50 healthy normal-weight young women. A Food Consumption Frequency Questionnaire (FCFQ) was used to classify them on the basis of their eating habits and preferences by principal component analysis (PCA). Based on the PCA, we defined two eating habit profiles, namely, prudent-type consumers (PTc, N = 25) and Western-type consumers (WTc, N = 25), i.e., low and high consumers of western diet (WD) foods, respectively. The first two PCA dimensions, PCA1 and PCA2, were associated with different psychological components of eating and brain responses in regions involved in reward and motivation (striatum), hedonic evaluation (orbitofrontal cortex, OFC), decision conflict (anterior cingulate cortex, ACC), and cognitive control of eating (prefrontal cortex). PCA1 was inversely correlated with the FC between the right nucleus accumbens and the left lateral OFC, while PCA2 was inversely correlated with the FC between the right insula and the ACC. Our results suggest that, among a healthy population, distinct eating profiles can be detected, with specific correlates in the psychological components of eating behavior, which are also related to a modulation in the reward and motivation system during food choices. We could detect different patterns in brain functioning at rest, with reduced connectivity between the reward system and the frontal brain region in Western-type food consumers, which might be considered as an initial change toward ongoing modified cortico-striatal control.

Monitoring blood-brain barrier status in a rat model of glioma receiving therapy: dual injection of low-molecular-weight and macromolecular MR contrast media.

PURPOSE: To evaluate the sequential injection of a low-molecular-weight (gadoterate meglumine [Gd-DOTA], 0.5 kDa) and a macromolecular (P846, 3.5 kDa) contrast media in monitoring the effect of antitumor therapies (antiangiogenic therapy and/or microbeam radiation therapy [MRT]) on healthy brain tissue and implanted tumors. MATERIALS AND METHODS: Animal use was compliant with official French guidelines and was assessed by the local Internal Evaluation Committee for Animal Welfare and Rights. Eighty male rats bearing 9L gliosarcoma were randomized into four groups: untreated, antiangiogenic (sorafenib) therapy, MRT, and both treatments. Magnetic resonance (MR) imaging was performed 1 day before and 1, 5, and 8 days after the start of the treatment. At all time points, vascular integrity to a macromolecular contrast medium (P846) and, 11 minutes 30 seconds later, to low-molecular-weight contrast medium (Gd-DOTA) was evaluated by using a dynamic contrast material-enhanced MR imaging approach. To quantify vessel wall integrity, areas under the signal intensity curves were computed for each contrast medium. Unpaired t tests and one-way analysis of variance were used for statistical analyses. RESULTS: Tumor vessels receiving antiangiogenic therapy became less permeable to the macromolecular contrast medium, but their permeability to the low-molecular-weight contrast medium remained unchanged. Healthy double-irradiated vessels became permeable to the low-molecular-weight contrast medium but not to the macromolecular contrast medium. CONCLUSION: Antiangiogenic therapy and MRT generate different effects on the extravasation of contrast medium in tumoral and healthy tissues. This study indicates that the use of a low-molecular-weight contrast medium and a macromolecular contrast medium provides complementary information and suggests that the use of two contrast media within the same MR imaging session is feasible.

A maternal Western diet during gestation and lactation modifies offspring's microglial cell density and morphology in the hippocampus and prefrontal cortex in Yucatan minipigs.

Changes in microglial development and morphology can be induced by inflammatory conditions and associated with eating or mood disorders, such as hyperphagia or depression. In a previous paper in the minipig model, we showed that maternal Western diet during gestation and lactation decreased hippocampus neurogenesis and food-rewarded cognitive abilities in the progeny. Whether these alterations are concomitant with a central inflammatory process in brain structures involved in learning and memory (hippocampus, HPC), cognitive (prefrontal cortex, PFC), or hedonic (orbitofrontal cortex, OFC) control of food intake is still unknown. In the present study, Yucatan minipigs (Sus scrofa) sows were exposed to two different diets during gestation and lactation (standard, SD N = 7 vs. Western diet, WD N = 9). Iba1 is a calcium-binding protein specifically expressed in microglia in the brain, which plays an important role in the regulation of the microglia function. Iba1 expression was examined by immunohistochemical analyses in the PFC, OFC and HPC of piglets. The density of microglial cells, as well as their morphology, were assessed in order to have an indirect insight of microglial cell activation state possibly in relationship with neuroinflammation. The density of Iba1-positive cells was higher in the PFC but not in the HPC of WD compared to SD piglets (p < 0.001). In the HPC, anterior and dorsolateral PFC, WD piglets had more unipolar cells, contrary to SD that had more multipolar cells (P < 0.0001). Opposite effects were observed in the OFC, with SD presenting more unipolar (P < 0.001) microglial cells compared to WD. We showed here that maternal diet during pregnancy and lactation had significant effects on morphological changes of microglial cells in the offspring, and that these effects differed between the HPC and PFC, suggesting different response mechanisms to the early nutritional environment.

Regular exposure to a Citrus-based sensory functional food ingredient alleviates the BOLD brain responses to acute pharmacological stress in a pig model of psychosocial chronic stress.

Psychosocial chronic stress is a critical risk factor for the development of mood disorders. However, little is known about the consequences of acute stress in the context of chronic stress, and about the related brain responses. In the present study we examined the physio-behavioural effects of a supplementation with a sensory functional food ingredient (FI) containing Citrus sinensis extract (D11399, Phodé, France) in a pig psychosocial chronic stress model. Female pigs underwent a 5- to 6-week stress protocol while receiving daily the FI (FI, n = 10) or a placebo (Sham, n = 10). We performed pharmacological magnetic resonance imaging (phMRI) to study the brain responses to an acute stress (injection of Synacthen®, a synthetic ACTH-related agonist) and to the FI odour with or without previous chronic supplementation. The olfactory stimulation with the ingredient elicited higher brain responses in FI animals, demonstrating memory retrieval and habituation to the odour. Pharmacological stress with Synacthen injection resulted in an increased activity in several brain regions associated with arousal, associative learning (hippocampus) and cognition (cingulate cortex) in chronically stressed animals. This highlighted the specific impact of acute stress on the brain. These responses were alleviated in animals previously supplemented by the FI during the entire chronic stress exposure. As chronic stress establishes upon the accumulation of acute stress events, any attenuation of the brain responses to acute stress can be interpreted as a beneficial effect, suggesting that FI could be a viable treatment to help individuals coping with repeated stressful events and eventually to reduce chronic stress. This study provides additional evidence on the potential benefits of this FI, of which the long-term consequences in terms of behaviour and physiology need to be further investigated.

Western diet, obesity and bariatric surgery sequentially modulated anxiety, eating patterns and brain responses to sucrose in adult Yucatan minipigs.

Palatable sweet/fatty foods overconsumption is a major risk factor for obesity and eating disorders, also having an impact on neuro-behavioural hedonic and cognitive components comparable to what is described for substance abuse. We hypothesized that Yucatan minipigs would show hedonic, cognitive, and affective neuro-behavioral shifts when subjected to western diet (WD) exposure without weight gain, after the onset of obesity, and finally after weight loss induced by caloric restriction with (RYGB) or without (Sham) gastric bypass. Eating behavior, cognitive and affective abilities were assessed with a spatial discrimination task (holeboard test) and two-choice feed tests. Brain responses to oral sucrose were mapped using 18F-FDG positron emission tomography. WD exposure impaired working memory and led to an "addiction-type" neuronal pattern involving hippocampal and cortical brain areas. Obesity induced anxiety-like behavior, loss of motivation, and snacking-type eating behavior. Weight loss interventions normalized the motivational and affective states but not eating behavior patterns. Brain glucose metabolism increased in gustatory (insula) and executive control (aPFC) areas after weight loss, but RYGB showed higher responses in inhibition-related areas (dorsal striatum). These results showed that diet quality, weight loss, and the type of weight loss intervention differently impacted brain responses to sucrose in the Yucatan minipig model.

fMRI-Based Brain Responses to Olfactory Stimulation with Two Putatively Orexigenic Functional Food Ingredients at Two Different Concentrations in the Pig Model.

Natural plant extracts are increasingly used as functional feed ingredients in animal husbandry and food ingredients in human alternative medicine to improve welfare and health. We investigated in 20 growing pigs via functional magnetic resonance imaging (fMRI) the brain blood oxygen level-dependent (BOLD) responses to olfactory stimulation with two sensory functional feed ingredients, A and B, at two different concentrations. Functional ingredient A contained extracts from Citrus sinensis (60% to 80%), and ingredient B contained a mixture of extracts Oreganum vulgarae (40% to 55%) and Cymbopogon flexuosus (20% to 25%). Increased concentration of ingredients induced a higher activation in reward and cognitive areas compared to lower concentrations. Moreover, considering both ingredients at the highest concentration, the ingredient A elicited higher brain responses in brain areas involved in hedonism/pleasantness compared to ingredient B, and more specifically in the caudate nucleus and orbitofrontal cortex. Our findings shed new light in the scope of emotion regulation through olfactory modulation via sensory functional ingredients, which opens the way to further preclinical studies in animal models and translational research in the context of nutrition, welfare, and health. PRACTICAL APPLICATION: Functional food/feed ingredients are gaining interest for improving health and welfare in humans and animals. Besides representing an alternative to antibiotics for example, food ingredients and their sensory characteristics might have a positive impact on emotions and consequently on well-being. Functional brain imaging in large animals such as in the pig model is a promising approach to investigate the central and behavioural effects of food ingredients, and determine the most effective blends and concentrations to modulate internal and emotional states.

Implementation of a New Food Picture Database in the Context of fMRI and Visual Cognitive Food-Choice Task in Healthy Volunteers.

This pilot study aimed at implementing a new food picture database in the context of functional magnetic resonance imaging (fMRI) cognitive food-choice task, with an internal conflict or not, in healthy normal-weight adults. The database contains 170 photographs including starters, main courses, and desserts; it presents a broad-spectrum of energy content and is provided with portion weight and nutritional information. It was tested in 16 participants who evaluated the energy density and gave a liking score for all food pictures via numerical scales. First, volunteers were segregated into two groups according to their eating habits according to a food consumption frequency questionnaire (FCFQ) to assess whether the database might elicit different appreciations according to individual eating habits. Second, participants underwent fMRI cognitive food-choice task (van der Laan et al., 2014), using our picture database, in which they had to choose between high-energy (HE) and low-energy (LE) foods, under a similar liking (SL, foods with similar hedonic appraisals) condition or a different liking (DL, foods with different hedonic appraisals) condition. Participants evaluated correctly the caloric content of dishes (from r = 0.72 to r = 0.79, P < 0.001), confirming a good perception of the caloric discrepancies between food pictures. Two subgroups based on FCFQ followed by a principal component analysis (PCA) and a hierarchical ascendant classification (HAC) were defined, that is, Prudent-type (PTc, N = 9) versus Western-type (WTc, N = 7) consumers, where the WTc group showed higher consumption of HE palatable foods than PTc (P < 0.05). The WTc group showed a higher correlation between liking and caloric evaluation of the food pictures as compared to PTc (r = 0.77 and r = 0.36, respectively, P < 0.001), confirming that food pictures elicited variable responses according to contrasted individual eating habits. The fMRI analyses showed that the DL condition elicited the activation of dorsal anterior cingulate cortex (dACC), involved in internal conflict monitoring, whereas SL condition did not, and that LE food choice involved high-level cognitive processes with higher activation of the hippocampus (HPC) and fusiform gyrus compared to HE food choice. Overall, this pilot study validated the use of the food picture database and fMRI-based procedure assessing decision-making processing during a food choice cognitive task with and without internal conflict.

Validation of a Psychosocial Chronic Stress Model in the Pig Using a Multidisciplinary Approach at the Gut-Brain and Behavior Levels.

Psychological chronic stress is an important risk factor for major depressive disorder, of which consequences have been widely studied in rodent models. This work aimed at describing a pig model of chronic stress based on social isolation, environmental impoverishment and unpredictability. Three groups of animals of both sexes were constituted. Two were exposed to the psychosocial stressors while receiving (SF, n = 12) or not (SC, n = 22) the antidepressant fluoxetine, and a third group (NSC, n = 22) remained unstressed. Animals were observed in home pens and during dedicated tests to assess resignation and anxiety-like behaviors. Brain structure and function were evaluated via proton MRS and fMRI. Hippocampal molecular biology and immunodetection of cellular proliferation (Ki67+) and neuron maturation (DCX+) in the dentate gyrus were also performed. Salivary cortisol, fecal short-chain fatty acids (SCFAs), and various plasmatic and intestinal biomarkers were analyzed. Compared to NSC, SC animals showed more resignation (p = 0.019) and had a higher level of salivary cortisol (p = 0.020). SC brain responses to stimulation by a novel odor were lower, similarly to their hippocampal neuronal density (p = 0.015), cellular proliferation (p = 0.030), and hippocampal levels of BDNF and 5-HT1AR (p = 0.056 and p = 0.007, respectively). However, the number of DCX+ cells was higher in the ventral dentate gyrus in this group (p = 0.025). In addition, HOMA-IR was also higher (p < 0.001) and microbiota fermentation activity was lower (SCFAs, SC/NSC: p < 0.01) in SC animals. Fluoxetine partially or totally reversed several of these effects. Exposure to psychosocial stressors in the pig model induced effects consistent with the human and rodent literature, including resignation behavior and alterations of the HPA axis and hippocampus. This model opens the way to innovative translational research exploring the mechanisms of chronic stress and testing intervention strategies with good face validity related to human.