Hedonic Brain Research Articles

Prebiotic diet changes neural correlates of food decision-making in overweight adults: a randomised controlled within-subject cross-over trial

ObjectiveAnimal studies suggest that prebiotic, plant-derived nutrients could improve homoeostatic and hedonic brain functions through improvements in microbiome–gut–brain communication. However, little is known if these results are applicable to humans....

Mapping the Homeostatic and Hedonic Brain Responses to Stevia Compared to Caloric Sweeteners and Water: A Double-Blind Randomised Controlled Crossover Trial in Healthy Adults.

Non-nutritive sweeteners have potential effects on brain function. We investigated neural correlates of responses to beverages differing in sweetness and calories. Healthy participants completed 4 randomised sessions: water vs. water with stevia, glucose, or maltodextrin. Blood-oxygenation level-dependent (BOLD) contrast was monitored for 30 min post-ingestion by functional Magnetic Resonance Imaging. A food visual probe task at baseline was repeated at 30 min. A significant interaction of taste-by-calories-by-time was demonstrated mainly in motor, frontal, and insula cortices. Consumption of the stevia-sweetened beverage resulted in greater BOLD decrease, especially in the 20–30 min period, compared to other beverages. There was a significant interaction of taste-by-time in BOLD response in gustatory and reward areas; sweet beverages induced greater reduction in BOLD compared to non-sweet. The interaction calories-by-time showed significantly greater incremental area under the curve in thalamic, visual, frontal, and parietal areas for glucose and maltodextrin 10–20 min post-consumption only, compared to water. In the visual cue task, the water demonstrated an increased response in the visual cortex to food images post-consumption; however, no difference was observed for the three sweet/caloric beverages. In conclusion, both sweet taste and calories exert modulatory effects, but stevia showed a more robust and prolonged effect.

Identification of an endocannabinoid gut-brain vagal mechanism controlling food reward and energy homeostasis.

The regulation of food intake, a sine qua non requirement for survival, thoroughly shapes feeding and energy balance by integrating both homeostatic and hedonic values of food. Unfortunately, the widespread access to palatable food has led to the development of feeding habits that are independent from metabolic needs. Among these, binge eating (BE) is characterized by uncontrolled voracious eating. While reward deficit seems to be a major contributor of BE, the physiological and molecular underpinnings of BE establishment remain elusive. Here, we combined a physiologically relevant BE mouse model with multiscale in vivo approaches to explore the functional connection between the gut-brain axis and the reward and homeostatic brain structures. Our results show that BE elicits compensatory adaptations requiring the gut-to-brain axis which, through the vagus nerve, relies on the permissive actions of peripheral endocannabinoids (eCBs) signaling. Selective inhibition of peripheral CB1 receptors resulted in a vagus-dependent increased hypothalamic activity, modified metabolic efficiency, and dampened activity of mesolimbic dopamine circuit, altogether leading to the suppression of palatable eating. We provide compelling evidence for a yet unappreciated physiological integrative mechanism by which variations of peripheral eCBs control the activity of the vagus nerve, thereby in turn gating the additive responses of both homeostatic and hedonic brain circuits which govern homeostatic and reward-driven feeding. In conclusion, we reveal that vagus-mediated eCBs/CB1R functions represent an interesting and innovative target to modulate energy balance and counteract food-reward disorders.

Amylin as a Future Obesity Treatment

Obesity is defined as abnormal or excessive fat accumulation that contributes to detrimental health impacts. One-third of the population suffers from obesity, and it is important to consider obesity as a chronic disease requiring chronic treatment. Amylin is co-secreted with insulin from β pancreatic cells upon nutrient delivery to the small intestine as a satiety signal, acts upon sub-cortical homeostatic and hedonic brain regions, slows gastric emptying, and suppresses post-prandial glucagon responses to meals. Therefore, new pharmacological amylin analogues can be used as potential anti-obesity medications in individuals who are overweight or obese. In this narrative review, we analyse the efficacy, potency, and safety of amylin analogues. The synthetic amylin analogue pramlintide is an approved treatment for diabetes mellitus which promotes better glycaemic control and small but significant weight loss. AM833 (cagrilintide), an investigational novel long-acting acylated amylin analogue, acts as a non-selective amylin receptor. This calcitonin G protein-coupled receptor agonist can serve as an attractive novel treatment for obesity, resulting in reduction of food intake and significant weight loss in a dose-dependent manner.

Glutamatergic projections from homeostatic to hedonic brain nuclei regulate intake of highly palatable food

Food intake is a complex behavior regulated by discrete brain nuclei that integrate homeostatic nutritional requirements with the hedonic properties of food. Homeostatic feeding (i.e. titration of caloric intake), is typically associated with hypothalamic brain nuclei, including the paraventricular nucleus of the hypothalamus (PVN). Hedonic feeding is driven, in part, by the reinforcing properties of highly palatable food (HPF), which is mediated by the nucleus accumbens (NAc). Dysregulation of homeostatic and hedonic brain nuclei can lead to pathological feeding behaviors, namely overconsumption of highly palatable food (HPF), that may drive obesity. Both homeostatic and hedonic mechanisms of food intake have been attributed to several brain regions, but the integration of homeostatic and hedonic signaling to drive food intake is less clear, therefore we aimed to identify the neuroanatomical, functional, and behavioral features of a novel PVN → NAc circuit. Using viral tracing techniques, we determined that PVN → NAc has origins in the parvocellular PVN, and that PVN → NAc neurons express VGLUT1, a marker of glutamatergic signaling. Next, we pharmacogenetically stimulated PVN → NAc neurons and quantified both gamma-aminobutyric acid (GABA) and glutamate release and phospho-cFos expression in the NAc and observed a robust and significant increase in extracellular glutamate and phospho-cFos expression. Finally, we pharmacogenetically stimulated PVN → NAc which decreased intake of highly palatable food, demonstrating that this glutamatergic circuitry regulates aspects of feeding.

Intragastric fructose administration interacts with emotional state in homeostatic and hedonic brain regions

ABSTRACT Background: Interoceptive properties of food may influence emotional state and its neural basis, as shown for fatty acids but remains unstudied for carbohydrates. Objectives: To study the effects of fructose and its interaction with sad emotion on brain activity in homeostatic and hedonic regions and investigate whether gut hormone responses can explain effects. Design: In 15 healthy subjects, brain activity for 40min after intragastric infusion of fructose (25g) or water was recorded using a cross-over pharmacological magnetic resonance imaging (phMRI) paradigm. Sad or neutral emotional states were induced by classical music and emotional facial expressions. Emotional state was assessed using the Self-Assessment Manikin. Blood samples were taken to assess gut hormone levels. Brain responses to fructose versus placebo, sad versus neutral emotion, and their interaction were analyzed over time in a single mask of a priori defined regions of interest at a voxel-level threshold of pFWEcorrected <0.05. Effects on emotion and hormones were tested using linear mixed models. Results: No main effects of fructose, emotion, or fructose-by-emotion interaction on emotional ratings were observed. Main effects of fructose, emotion and aninteraction effect were found on brain activity (medulla, midbrain, hypothalamus, basal ganglia, anterior insula, orbitofrontal cortex, anterior cingulate cortex and amygdala). An increase in circulating GLP-1 after fructose in neutral emotion was abolished during sad emotion (fructose-by-emotion-by-time, p=0.041). Ghrelin levels were higher in sad emotion (time-by-emotion, p=0.037). Conclusions: Emotional state interacts with brain and endocrine responses to intragastric infusion of 25 g of fructose, however such an effect was not found at behavioral level. Trial registration: ClinicalTrials.gov identifier: NCT02946983.

O5.5. THE NEUROBIOLOGY OF NEGATIVE SYMPTOMS IN SCHIZOPHRENIA: MULTI-MODAL PET AND FMRI FINDINGS

BackgroundThe neurobiological mechanisms underlying anhedonia and other negative symptoms in schizophrenia are unknown. Understanding this would help identify treatments for these symptoms. Pre-clinical and human evidence shows the mu-opioid receptor plays a key role in reward processing and anhedonia. However, the contribution of Mu Opioid Receptor (MOR) signalling to negative symptoms and the reward processing abnormalities in schizophrenia is unknown. Here, we investigated for the first time in vivo in patients whether MOR availability is altered in schizophrenia and if this is associated with the neural processes underlying reward anticipation in patients with schizophrenia using multimodal neuroimaging.MethodsForty volunteers (n=20 patients with schizophrenia and 20 age and sex-matched healthy controls) received an [11C]-carfentanil PET scan to measure MOR availability, a structural MRI scan and a functional MRI scan while performing the Monetary Incentive Delay (MID) task to measure the neural response to reward anticipation. All the patients met criteria for persistent negative symptoms. Our primary ROI for the PET analysis was the striatum. In addition, we analysed MOR availability in brain regions in the hedonic network (the striatum, insula and anterior cingulate cortex). The fMRI analysis focused on brain regions in this hedonic network as these have previously associated with MOR mediated reward processing in humans and preclinical studies. Brain volumes of regions of interest (ROIs) were also extracted.ResultsThe analysis showed significantly lower MOR availability in the striatum of patients with schizophrenia relative to controls (patients vs. controls (mean binding potential (BPND) ± SEM): 1.54 ± 0.06 vs. 1.7 ± 0.05, Cohen’s d= 0.7, t=-2.2, df (37), p<0.05). There was also a significant effect of both group (F (5, 222) = 334.5, p<0.05) and ROI (F (1, 222) = 5.65, p<0.05) on BPND measures in the hedonic brain network. The group* ROI interaction was not significant (F (5, 222) = 0.2167, p>0.05). There were no significant differences in the volume of the striatum or other brain regions between groups (patients vs controls: mean ± SEM (mm3) 13019 ± 302 vs 12937 ± 327 respectively, p = 0.86).Reward anticipation in controls was associated with increased neural activation in a widespread network of brain regions including the ventral striatum and insula. The activation in the ventral striatum was significantly lower in patients compared to healthy controls. MOR availability was positively correlated with neural activation in the insula during reward anticipation in controls (spearman’s rho=0.6, p=0.006) but not in patients (spearman’s rho=0.13, p=0.57). In contrast, MOR availability in the striatum was not associated with neural activation in the striatum.DiscussionThese data show for the first time in vivo that mu-opioid receptor availability is lower in schizophrenia across the hedonic brain network. Moreover, patients with schizophrenia show altered coupling between mu-opioid signalling in the insula and brain activation during reward anticipation. These findings identify the mu-opioid receptor as a potential therapeutic target for reward dysfunction in schizophrenia.

Expression of neural markers of gustatory signaling are differentially altered by continuous and intermittent feeding patterns

Food intake patterns are regulated by signals from the gustatory neural circuit, a complex neural network that begins at the tongue and continues to homeostatic and hedonic brain regions involved in eating behavior. The goal of the current study was to investigate the short-term effects of continuous access to a high fat diet (HFD) versus limited access to dietary fat on the gustatory neural circuit. Male Sprague-Dawley rats were fed a chow diet, a HFD (56% kcal from fat), or provided limited, daily (2 h/day) or limited, intermittent (2 h/day, 3 times/week) access to vegetable shortening for 2 weeks. Real time PCR was used to determine mRNA expression of markers of fat sensing/signaling (e.g. CD36) on the circumvallate papillae, markers of homeostatic eating in the mediobasal hypothalamus (MBH) and markers of hedonic eating in the nucleus accumbens (NAc). Continuous HFD increased mRNA levels of lingual CD36 and serotonin signaling, altered markers of homeostatic and hedonic eating. Limited, intermittent access to dietary fat selectively altered the expression of genes associated with the regulation of dopamine signaling. Overall, these data suggest that short-term, continuous access to HFD leads to altered fat taste and decreased expression of markers of homeostatic and hedonic eating. Limited, intermittent access, or binge-like, consumption of dietary fat led to an overall increase in markers of hedonic eating, without altering expression of lingual fat sensors or homeostatic eating. These data suggest that there are differential effects of meal patterns on gustatory neurocircuitry which may regulate the overconsumption of fat and lead to obesity.

Dissociation between the processing of humorous and monetary rewards in the \u2018motivation\u2019 and \u2018hedonic\u2019 brains

Humor elicits feelings of amusement and can be thought of as a social reward. We identified distinct mesolimbic reward system (MRS) processing patterns for monetary and humorous rewards. During both the reward anticipation and outcome phases, the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) were active in response to monetary cues and monetary gains, while the amygdala and midbrain showed a differential response to humorous rewards, apparently driven by the hedonic enjoyment and appreciation of humor consumption. Psychophysiological interaction analysis (PPI) further demonstrated the functional coupling of the amygdala-midbrain circuit in response to humorous gains during the reward outcome phase, while neural signaling was observed in the NAc-ACC circuit during both the reward anticipation and outcome phases in response to monetary rewards. This is consistent with a view in which the NAc plays a key role in the ‘motivation brain’, and the amygdala in the ‘hedonic brain’. The findings further suggest that the neural mechanisms underlying reward consumption are more modality-specific than those underlying reward anticipation. Our study contributes to a growing understanding of neural responses to social rewards and represent an important first step toward understanding the neural processing of humor as one significant type of social reward.

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.

Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms

Objectives: Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects.Methods: Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women. Appetite-related sensations, plasma levels of gastrointestinal hormones and hedonic food intake (ad libitum drink test) were assessed.Results: Lower octanoylated ghrelin (P<0.04), total ghrelin (P<0.01), and motilin (P<0.01) plasma levels were found after QHCl administration, along with lower prospective food consumption ratings (P<0.02) and hedonic food intake (P<0.05). QHCl increased neural activity in the hypothalamus and hedonic (anterior insula, putamen, caudate, pallidum, amygdala, anterior cingulate cortex, orbitofrontal cortex, midbrain) regions, but decreased activity in the homeostatic medulla (all pFWE-corrected<0.05). Differential brain responses to QHCl versus placebo covaried with subjective and hormonal responses and predicted differences in hedonic food intake.Discussion: Intragastric QHCl decreases prospective and actual food intake in healthy women by interfering with homeostatic and hedonic brain circuits in a ghrelin- and motilin-mediated fashion. These findings suggest a potential of bitter tastants to reduce appetite and food intake, through the gut-brain axis.

The habenula as a novel link between the homeostatic and hedonic pathways in cancer-associated weight loss: a pilot study.

BackgroundLittle is known about the brain mechanisms underlying cancer‐associated weight loss (C‐WL) in humans despite this condition negatively affecting their quality of life and survival. We tested the hypothesis that patients with C‐WL have abnormal connectivity in homeostatic and hedonic brain pathways together with altered brain activity during food reward.MethodsIn 12 patients with cancer and 12 healthy controls, resting‐state functional connectivity (RSFC, resting brain activity observed through changes in https://en.wikipedia.org/wiki/Cerebral_blood_flow in the brain which creates a https://en.wikipedia.org/wiki/Blood-oxygen-level_dependent signal that can be measured using https://en.wikipedia.org/wiki/Functional_magnetic_resonance_imaging) was used to compare three brain regions hypothesized to play a role in C‐WL: the hypothalamus (homeostatic), the nucleus accumbens (hedonic), and the habenula (an important regulator of reward). In addition, the brain reward response to juice was studied.Participants included 12 patients with histological diagnosis of incurable cancer (solid tumours), a European Cooperative Oncology Group performance status of 0–2, and a ≥5% involuntary body weight loss from pre‐illness over the previous 6 months and 12 non‐cancer controls matched for age, sex, and race. RSFC between the hypothalamus, nucleus accumbens, and habenula and brain striatum activity as measured by functional MRI during juice reward delivery events were the main outcome measures.ResultsAfter adjusting for BMI and compared with matched controls, patients with C‐WL were found to have reduced RSFC between the habenula and hypothalamus (P = 0.04) and between the habenula and nucleus accumbens (P = 0.014). Patients with C‐WL also had reduced juice reward responses in the striatum compared with controls.ConclusionsIn patients with C‐WL, reduced connectivity between both homeostatic and hedonic brain regions and the habenula and reduced juice reward were observed. Further research is needed to establish the relevance of the habenula and striatum in C‐WL.

Tuning down the hedonic brain: Cognitive load reduces neural responses to high-calorie food pictures in the nucleus accumbens

The present research examined whether cognitive load modulates the neural processing of appetitive, high-calorie food stimuli. In a functional magnetic resonance imaging (fMRI) study, participants quickly categorized high-calorie and low-calorie food pictures versus object pictures as edible or inedible while they concurrently performed a digit-span task that varied between low and high cognitive load (memorizing six digits vs. one digit). In line with predictions, the digit-span task engaged the dorsolateral prefrontal cortex (DLPFC) when cognitive load was high compared to low. Moreover, exposure to high-calorie compared to low-calorie food pictures led to increased activation in the nucleus accumbens (NAcc), but only when cognitive load was low and not when it was high. In addition, connectivity analyses showed that load altered the functional coupling between NAcc and right DLPFC during presentation of the high-calorie versus low-calorie food pictures. Together, these findings indicate that loading the cognitive system moderates hedonic brain responses to high-calorie food pictures via interactions between NAcc and DLPFC. Our findings are consistent with the putative cognitive nature of food motivation. Implications for future research are discussed.

Obesity, body weight regulation and the brain: insights from fMRI.

Obesity constitutes a major global health threat. Despite the success of bariatric surgery in delivering sustainable weight loss and improvement in obesity-related morbidity, effective non-surgical treatments are urgently needed, necessitating an increased understanding of body weight regulation. Neuroimaging studies undertaken in people with healthy weight, overweight, obesity and following bariatric surgery have contributed to identifying the neurophysiological changes seen in obesity and help increase our understanding of the mechanisms driving the favourable eating behaviour changes and sustained weight loss engendered by bariatric surgery. These studies have revealed a key interplay between peripheral metabolic signals, homeostatic and hedonic brain regions and genetics. Findings from brain functional magnetic resonance imaging (fMRI) studies have consistently associated obesity with an increased motivational drive to eat, increased reward responses to food cues and impaired food-related self-control processes. Interestingly, new data link these obesity-associated changes with structural and connectivity changes within the central nervous system. Moreover, emerging data suggest that bariatric surgery leads to neuroplastic recovery. A greater understanding of the interactions between peripheral signals of energy balance, the neural substrates that regulate eating behaviour, the environment and genetics will be key for the development of novel therapeutic strategies for obesity. This review provides an overview of our current understanding of the pathoaetiology of obesity with a focus upon the role that fMRI studies have played in enhancing our understanding of the central regulation of eating behaviour and energy homeostasis.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Perinatal Western Diet Consumption Leads to Profound Plasticity and GABAergic Phenotype Changes within Hypothalamus and Reward Pathway from Birth to Sexual Maturity in Rat.

Perinatal maternal consumption of energy dense food increases the risk of obesity in children. This is associated with an overconsumption of palatable food that is consumed for its hedonic property. The underlying mechanism that links perinatal maternal diet and offspring preference for fat is still poorly understood. In this study, we aim at studying the influence of maternal high-fat/high-sugar diet feeding [western diet (WD)] during gestation and lactation on the reward pathways controlling feeding in the rat offspring from birth to sexual maturity. We performed a longitudinal follow-up of WD and Control offspring at three critical time periods (childhood, adolescence, and adulthood) and focus on investigating the influence of perinatal exposure to palatable diet on (i) fat preference, (ii) gene expression profile, and (iii) neuroanatomical/architectural changes of the mesolimbic dopaminergic networks. We showed that WD feeding restricted to the perinatal period has a clear long-lasting influence on the organization of homeostatic and hedonic brain circuits but not on fat preference. We demonstrated a period specific evolution of the preference for fat that we correlated with specific brain molecular signatures. In offspring from WD fed dams, we observed during childhood the existence of fat preference associated with a higher expression of key gene involved in the dopamine (DA) systems; at adolescence, a high-fat preference for both groups, progressively reduced during the 3 days test for the WD group and associated with a reduced expression of key gene involved in the DA systems for the WD group that could suggest a compensatory mechanism to protect them from further high-fat exposure; and finally at adulthood, a preference for fat that was identical to control rats but associated with profound modification in key genes involved in the γ-aminobutyric acid network, serotonin receptors, and polysialic acid–NCAM-dependent remodeling of the hypothalamus. Altogether, these data reveal that maternal WD, restricted to the perinatal period, has no sustained impact on energy homeostasis and fat preference later in life even though a strong remodeling of the hypothalamic homeostatic and reward pathway involved in eating behavior occurred. Further functional experiments would be needed to understand the relevance of these circuits remodeling.

Food Addiction: A Short Review

Neurotransmitters are essential for humans' body to work properly. There is a hedonic brain circuit composed of centers that work together to enable these neurotransmitters to control the state of pleasure: dopamine and serotonin. All drug abuse increases dopamine levels in the extracellular medium. Several times dependence occur behaviorally, and in a less proportion by substance. On this review is going to be approached food addiction.

Deficits in autonomic indices of emotion regulation and reward processing associated with prescription opioid use and misuse.

Prescription opioid misuse and high-dose opioid use may result in allostatic dysregulation of hedonic brain circuitry, leading to reduced emotion regulation capacity. In particular, opioid misuse may blunt the ability to experience and upregulate positive affect from natural rewards. The purpose of this study was to examine associations between opioid use/misuse and autonomic indices of emotion regulation capability in a sample of chronic pain patients receiving prescription opioid pharmacotherapy. Chronic pain patients taking long-term opioid analgesics (N=40) completed an emotion regulation task while heart rate variability (HRV) was recorded, and also completed self-report measures of opioid misuse, craving, pain severity, and emotional distress. Based on a validated cut-point on the Current Opioid Misuse Measure, participants were grouped as opioid misusers or non-misusers. Opioid misuse status and morphine equivalent daily dose (MEDD) were examined as predictors of HRV and self-reports of emotion regulation. Opioid misusers exhibited significantly less HRV during positive and negative emotion regulation, and significantly less positive effect, than non-misusers, after controlling for confounders including pain severity and emotional distress. MEDD was inversely associated with positive emotion regulation efficacy. Findings implicate the presence of reward processing deficits among chronic pain patients with opioid-misusing behaviors, and opioid dosage was associated with deficient emotion regulation, suggesting the presence of compromised top-down cognitive control over bottom-up hedonic processes. Emotion regulation among opioid misusers may represent an important treatment target.

The hedonic and hungry brain: Nutritional, hormonal, surgical and genetic modulation of human food reward

The hedonic and hungry brain: Nutritional, hormonal, surgical and genetic modulation of human food reward

Altered Brain Response to Drinking Glucose and Fructose in Obese Adolescents.

Increased sugar-sweetened beverage consumption has been linked to higher rates of obesity. Using functional MRI, we assessed brain perfusion responses to drinking two commonly consumed monosaccharides, glucose and fructose, in obese and lean adolescents. Marked differences were observed. In response to drinking glucose, obese adolescents exhibited decreased brain perfusion in brain regions involved in executive function (prefrontal cortex [PFC]) and increased perfusion in homeostatic appetite regions of the brain (hypothalamus). Conversely, in response to drinking glucose, lean adolescents demonstrated increased PFC brain perfusion and no change in perfusion in the hypothalamus. In addition, obese adolescents demonstrated attenuated suppression of serum acyl-ghrelin and increased circulating insulin level after glucose ingestion; furthermore, the change in acyl-ghrelin and insulin levels after both glucose and fructose ingestion was associated with increased hypothalamic, thalamic, and hippocampal blood flow in obese relative to lean adolescents. Additionally, in all subjects there was greater perfusion in the ventral striatum with fructose relative to glucose ingestion. Finally, reduced connectivity between executive, homeostatic, and hedonic brain regions was observed in obese adolescents. These data demonstrate that obese adolescents have impaired prefrontal executive control responses to drinking glucose and fructose, while their homeostatic and hedonic responses appear to be heightened. Thus, obesity-related brain adaptations to glucose and fructose consumption in obese adolescents may contribute to excessive consumption of glucose and fructose, thereby promoting further weight gain.