Brain Reward Responses Research Articles

The Role of Glucocorticoid and Nicotinic Acetylcholine Receptors in the Reward-Enhancing Effects of Nicotine in the ICSS Procedure in Male and Female Rats.

Tobacco use disorder is a chronic disorder that affects more than one billion people worldwide and causes the death of millions each year. The rewarding properties of nicotine are critical for the initiation of smoking. Previous research has shown that the activation of glucocorticoid receptors (GRs) plays a role in nicotine self-administration in rats. However, the role of GRs in the acute rewarding effects of nicotine are unknown. In this study, we investigated the effects of the GR antagonist mifepristone and the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine on the reward-enhancing effects of nicotine using the intracranial self-stimulation (ICSS) procedure in adult male and female rats. The rats were prepared with ICSS electrodes in the medial forebrain bundle and then trained on the ICSS procedure. Nicotine lowered the brain reward thresholds and decreased response latencies similarly in male and female rats. These findings suggest that nicotine enhances the rewarding effects of ICSS and has stimulant properties. Treatment with the GR antagonist mifepristone did not affect the reward-enhancing effects of nicotine but increased response latencies, suggesting a sedative effect. Mecamylamine did not affect the brain reward thresholds or response latencies of the control rats, but prevented the nicotine-induced decrease in brain reward thresholds and reward latencies. These findings indicate that the rewarding effects of nicotine are mediated via the activation of nAChRs, and that the activation of GRs does not contribute to the acute rewarding effects of nicotine. These studies enhance our understanding of the neurobiological mechanisms underlying tobacco use disorder.

Blunted midbrain reward activation during smoking withdrawal: a preliminary study.

Tobacco smoking is the leading preventable cause of death, causing more than six million deaths annually worldwide, mainly due to cardiovascular disease and cancer. Many habitual smokers try to stop smoking but only about 7% are successful, despite widespread knowledge of the risks. Development of addiction to a range of substances is associated with progressive blunting of brain reward responses and sensitisation of stress responses, as described by the allostasis theory of addiction. There is pre-clinical evidence from rodents for a dramatic decrease in brain reward function during nicotine withdrawal. Here we tested the hypothesis that habitual smokers would also exhibit blunted reward function during nicotine withdrawal using a decision-making task and fMRI. Our findings supported this hypothesis, with midbrain reward-related responses particularly blunted. We also tested the hypothesis that smokers with a longer duration of smoking would have more pronounced abnormalities. Contrary to expectations, we found that a shorter duration of smoking in younger smokers was associated with the most marked abnormalities, with blunted midbrain reward related activation including the dopaminergic ventral tegmental area. Given the substantial mortality associated with smoking, and the small percent of people who manage to achieve sustained abstinence, further translational studies on nicotine addiction mechanisms are indicated.

Replication of neural responses to monetary incentives and exploration of reward-influenced network connectivity in fibromyalgia

Neuroimaging research has begun to implicate alterations of brain reward systems in chronic pain. Previously, using functional magnetic resonance imaging (fMRI) and a monetary incentive delay (MID) task, Martucci et al. (2018) showed that neural responses to reward anticipation and outcome are altered in fibromyalgia. In the present study, we aimed to test the replicability of these altered neural responses to reward in a separate fibromyalgia cohort. In addition, the present study was conducted at a distinct U.S. location but involved a similar study design. For the present study, 20 patients with fibromyalgia and 20 healthy controls participated in MID task fMRI scan procedures and completed clinical/psychological questionnaires. fMRI analyses comparing patient and control groups revealed a consistent trend of main results which were largely similar to the prior reported results. Specifically, in the replication fibromyalgia cohort, medial prefrontal cortex (MPFC) response was reduced during gain anticipation and was increased during no-loss (non-punishment) outcome compared to controls. Also consistent with previous findings, the nucleus accumbens response to gain anticipation did not differ in patients vs. controls. Further, results from similarly-designed behavioral, correlational, and exploratory analyses were complementary to previous findings. Finally, a novel network-based functional connectivity analysis of the MID task fMRI data across patients vs. controls implied enhanced connectivity within the default mode network in participants with fibromyalgia. Together, based on replicating prior univariate results and new network-based functional connectivity analyses of MID task fMRI data, we provide further evidence of altered brain reward responses, particularly in the MPFC response to reward outcomes, in patients with fibromyalgia.

Brain reward response in adolescents and young adults with anorexia nervosa is moderated by changes in body weight and sweetness perception.

Anorexia nervosa (AN) is a severe psychiatric illness with complex etiology. Recently, we found elevated striatal brain response to sweet taste stimuli in adolescents and young adults with AN. Here, we tested the hypothesis that nutritional rehabilitation normalizes prediction error activation, a measure for dopamine-related reward circuit response, to salient caloric taste stimuli in AN. A total of 28 individuals with AN (age=16 ± 2 years; body mass index [BMI]=16 ± 1) who previously underwent brain imaging while performing a taste prediction error task using sucrose as salient caloric stimulus, participated in a second brain imaging scan (BMI=18 ± 1) after intensive specialized eating disorder treatment (41 ± 15 days). A total of 31 healthy controls (age=16 ± 3 years; BMI=21 ± 2) were also studied on two occasions. At baseline, individuals with AN demonstrated an elevated salience response in bilateral caudate head and nucleus accumbens, and right ventral striatum. At the second scan, elevated response was only found in the right nucleus accumbens. A moderator analysis indicated that greater increase in BMI and greater decrease in sweetness perception predicted lesser prediction error response at the second scan in AN. Consistent with the previously reported monetary stimulus-response, elevated taste prediction error response in AN was largely absent after weight restoration. This study indicates that changes in BMI and sweet taste perception are independent moderators of change of brain salience response in adolescents and young adults with AN. The study points toward dynamic changes in the brain reward circuitry in AN and highlights the importance of nutrition and weight restoration in that process. AN is a severe psychiatric illness. Biological factors that integrate neurobiology and behavior could become important targets to improve treatment outcome. This study highlights the importance of weight normalization and taste perception the normalization of brain function, and food type or taste-specific interventions could help in the recovery process. Furthermore, the study suggests that food-related and nonfood-related reward processing adapts to illness state in AN.

Efficacy of a food response and attention training treatment for obesity: A randomized placebo controlled trial

Elevated brain reward and attention region response, and weaker inhibitory region response to high-calorie foods has predicted future weight gain, suggesting that an intervention that reduces reward and attention region response and increases inhibitory region response to such foods might reduce overeating. We conducted a randomized controlled trial to test whether a multi-faceted food response and attention training protocol with personalized high- and low-calorie food images would reduce body fat and valuation and reward region response to high-calorie foods compared to a placebo control training protocol with non-food images in an effort to replicate findings from two past trials. Participants were community-recruited adults with overweight/obesity (N = 179; M age = 27.7 ± 7.0) who completed assessments at pretest, posttest, 3-month, 6-month, and 12-month follow-ups. Participants randomized to the food response inhibition and attention training showed significantly greater increases in palatability ratings of low-calorie foods than controls (d = 0.27) at posttest, but did not show body fat loss, reductions in palatability ratings and monetary valuation, or reward region response, to high-calorie foods. The lack of expected effects appears to be related to weaker learning compared to the learning in past trials, potentially because we used more heterogenous high-calorie and low-calorie food images in the present training.

More than Addiction—The Nucleus Accumbens Contribution to Development of Mental Disorders and Neurodegenerative Diseases

Stress and negative emotions evoked by social relationships and working conditions, frequently accompanied by the consumption of addictive substances, and metabolic and/or genetic predispositions, negatively affect brain function. One of the affected structures is nucleus accumbens (NAc). Although its function is commonly known to be associated with brain reward responses and addiction, a growing body of evidence also suggests its role in some mental disorders, such as depression and schizophrenia, as well as neurodegenerative diseases, such as Alzheimer’s, Huntington’s, and Parkinson’s. This may result from disintegration of the extensive connections based on numerous neurotransmitter systems, as well as impairment of some neuroplasticity mechanisms in the NAc. The consequences of NAc lesions are both morphological and functional. They include changes in the NAc’s volume, cell number, modifications of the neuronal dendritic tree and dendritic spines, and changes in the number of synapses. Alterations in the synaptic plasticity affect the efficiency of synaptic transmission. Modification of the number and structure of the receptors affects signaling pathways, the content of neuromodulators (e.g., BDNF) and transcription factors (e.g., pCREB, DeltaFosB, NFκB), and gene expression. Interestingly, changes in the NAc often have a different character and intensity compared to the changes observed in the other parts of the basal ganglia, in particular the dorsal striatum. In this review, we highlight the role of the NAc in various pathological processes in the context of its structural and functional damage, impaired connections with the other brain areas cooperating within functional systems, and progression of the pathological processes.

Bacteroides uniformis CECT 7771 Modulates the Brain Reward Response to Reduce Binge Eating and Anxiety-Like Behavior in Rat

Food addiction (FA) is characterized by behavioral and neurochemical changes linked to loss of food intake control. Gut microbiota may influence appetite and food intake via endocrine and neural routes. The gut microbiota is known to impact homeostatic energy mechanisms, but its role in regulating the reward system is less certain. We show that the administration of Bacteroides uniformis CECT 7771 (B. uniformis) in a rat FA model impacts on the brain reward response, ameliorating binge eating and decreasing anxiety-like behavior. These effects are mediated, at least in part, by changes in the levels of dopamine, serotonin, and noradrenaline in the nucleus accumbens and in the expression of dopamine D1 and D2 receptors in the prefrontal cortex and intestine. B. uniformis reverses the fasting-induced microbiota changes and increases the abundance of species linked to healthy metabolotypes. Our data indicate that microbiota-based interventions might help to control compulsive overeating by modulating the reward response.

Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders

Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking. To assess brain response during unexpected receipt or omission of a salient sweet stimulus across a large sample of individuals with eating disorders and healthy controls and test for evidence of whether this brain response is associated with the ventral striatal-hypothalamic circuitry, which has been associated with food intake control, and whether salient stimulus response and eating disorder related behaviors are associated. In this cross-sectional functional brain imaging study, young adults across the eating disorder spectrum were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classic conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error. Dynamic effective connectivity during expected sweet taste receipt was studied to investigate hierarchical brain activation between food intake relevant brain regions. The study was conducted from June 2014 to November 2019. Data were analyzed from December 2019 to February 2020. Prediction error brain reward response across insula and striatum; dynamic effective connectivity between hypothalamus and ventral striatum; and demographic and behavior variables and their correlations with prediction error brain response and connectivity edge coefficients. Of 317 female participants (197 with eating disorders and 120 healthy controls), the mean (SD) age was 23.8 (5.6) years and mean (SD) body mass index was 20.8 (5.4). Prediction error response was elevated in participants with anorexia nervosa (Wilks λ, 0.843; P = .001) and in participants with eating disorders inversely correlated with body mass index (left nucleus accumbens: r = -0.291; 95% CI, -0.413 to -0.167; P < .001; right dorsal anterior insula: r = -0.228; 95% CI, -0.366 to -0.089; P = .001), eating disorder inventory-3 binge eating tendency (left nucleus accumbens: r = -0.207; 95% CI, -0.333 to -0.073; P = .004; right dorsal anterior insula: r = -0.220; 95% CI, -0.354 to -0.073; P = .002), and trait anxiety (left nucleus accumbens: r = -0.148; 95% CI, -0.288 to -0.003; P = .04; right dorsal anterior insula: r = -0.221; 95% CI, -0.357 to -0.076; P = .002). Ventral striatal to hypothalamus directed connectivity was positively correlated with ventral striatal prediction error in eating disorders (r = 0.189; 95% CI, 0.045-0.324; P = .01) and negatively correlated with feeling out of control after eating (right side: r = -0.328; 95% CI, -0.480 to -0.164; P < .001; left side: r = -0.297; 95% CI, -0.439 to -0.142; P = .001). The results of this cross-sectional imaging study support that body mass index modulates prediction error and food intake control circuitry in the brain. Once altered, this circuitry may reinforce eating disorder behaviors when paired with behavioral traits associated with overeating or undereating.

Persistence, Reward Dependence, and Sensitivity to Reward Are Associated With Unexpected Salience Response in Girls but Not in Adult Women: Implications for Psychiatric Vulnerabilities

BackgroundAdolescence is a critical period for the development of not only personality but also psychopathology. These processes may be specific to sex, and brain reward circuits may have a role. Here, we studied how reward processing and temperament associations differ across adolescent and adult females. MethodsA total of 29 adolescent girls and 41 adult women completed temperament assessments and performed a classical taste conditioning paradigm during brain imaging. Data were analyzed for the dopamine-related prediction error response. In addition, unexpected stimulus receipt or omission and expected receipt response were also analyzed. Heat maps identified cortical-subcortical brain response associations. ResultsAdolescents showed stronger prediction error and unexpected receipt and omission responses (partial η2 = 0.063 to 0.166; p = .001 to .043) in insula, orbitofrontal cortex (OFC), and striatum than adults. Expected stimulus receipt response was similar between groups. In adolescents versus adults, persistence was more strongly positively related to prediction error (OFC, insula, striatum; Fisher’s z = 1.704 to 3.008; p = .001 to .044) and unexpected stimulus receipt (OFC, insula; Fisher’s z = 1.843 to 2.051; p = .014 to .033) and negatively with omission (OFC, insula, striatum; Fisher’s z = −1.905 to −3.069; p = .001 to .028). Reward sensitivity and reward dependence correlated more positively with unexpected stimulus receipt and more negatively with stimulus omission response in adolescents. Adolescents showed significant correlations between the striatum and FC for unexpected stimulus receipt and omission that correlated with persistence but were absent in adults. ConclusionsAssociations between temperamental traits and brain reward response may provide neurotypical markers that contribute to developing adaptive or maladaptive behavior patterns when transitioning from adolescence to adulthood.

In the nose or on the tongue? Contrasting motivational effects of oral and intranasal oxytocin on arousal and reward during social processing

Intranasal oxytocin exerts wide-ranging effects on socioemotional behavior and is proposed as a potential therapeutic intervention in psychiatric disorders. However, following intranasal administration, oxytocin could penetrate directly into the brain or influence its activity via increased peripheral concentrations crossing the blood–brain barrier or influencing vagal projections. In the current randomized, placebo-controlled, pharmaco-imaging clinical trial we investigated effects of 24IU oral (lingual) oxytocin spray, restricting it to peripherally mediated blood-borne and vagal effects, on responses to face emotions in 80 male subjects and compared them with 138 subjects treated intranasally with 24IU. Oral, but not intranasal oxytocin administration increased both arousal ratings for faces and associated brain reward responses, the latter being partially mediated by blood concentration changes. Furthermore, while oral oxytocin increased amygdala and arousal responses to face emotions, after intranasal administration they were decreased. Thus, oxytocin can produce markedly contrasting motivational effects in relation to socioemotional cues when it influences brain function via different routes. These findings have important implications for future therapeutic use since administering oxytocin orally may be both easier and have potentially stronger beneficial effects by enhancing responses to emotional cues and increasing their associated reward.

A duodenal sleeve bypass device added to intensive medical therapy for obesity with type 2 diabetes: a RCT

BackgroundThe EndoBarrier®(GI Dynamics Inc., Boston, MA, USA) is an endoluminal duodenal–jejunal bypass liner developed for the treatment of patients with obesity and type 2 diabetes mellitus. Meta-analyses of its effects on glycaemia and weight have called for larger randomised controlled trials with longer follow-up.ObjectivesThe primary objective was to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level reduction of ≥ 20%. The secondary objectives were to compare intensive medical therapy with a duodenal–jejunal bypass liner with intensive medical therapy without a duodenal–jejunal bypass liner, comparing effectiveness on the metabolic state as defined by the International Diabetes Federation as a glycated haemoglobin level of &lt; 42 mmol/mol, blood pressure of &lt; 135/85 mmHg, and the effectiveness on total body weight loss. Additional secondary outcomes were to investigate the cost-effectiveness and mechanism of action of the effect of a duodenal–jejunal bypass liner on brain reward system responses, insulin sensitivity, eating behaviour and metabonomics.DesignA multicentre, open-label, randomised controlled trial.SettingImperial College Healthcare NHS Trust and University Hospital Southampton NHS Foundation Trust.ParticipantsPatients aged 18–65 years with a body mass index of 30–50 kg/m2and with inadequately controlled type 2 diabetes mellitus who were on oral glucose-lowering medications.InterventionsParticipants were randomised equally to receive intensive medical therapy alongside a duodenal–jejunal bypass liner device (n = 85) or intensive medical therapy alone for 12 months (n = 85), and were followed up for a further 12 months.ResultsThere was no significant difference between groups in the percentage of patients achieving the glycaemic primary or secondary outcomes [primary outcome at 12 months: duodenal–jejunal bypass liner group 54.5% vs. control group 55.2% (odds ratio 0.93, 95% confidence interval 0.44 to 1.98;p = 0.85); primary outcome at 24 months: duodenal–jejunal bypass liner group 39.7% vs. control group 36.5% (odds ratio 1.13, 95% confidence interval 0.52 to 2.47;p = 0.75)]. Significantly more patients in the duodenal–jejunal bypass liner group than in the control group lost &gt; 15% of their total body weight (duodenal–jejunal bypass liner group 24.2% vs. control group 3.7%; odds ratio 8.33, 95% confidence interval 1.78 to 39.0;p = 0.007) and achieved blood pressure targets (duodenal–jejunal bypass liner group 68.2% vs. control group 44.4%; odds ratio 2.57, 95% confidence interval 1.21 to 5.48;p = 0.014). These differences were observed at 12 months but not at 24 months. There were more adverse events in the duodenal–jejunal bypass liner group, including one liver abscess. The increase in peripheral insulin sensitivity was superior in the duodenal–jejunal bypass liner group. Spectroscopic analyses of plasma, urine and faeces revealed several distinct metabolic perturbations in the duodenal–jejunal bypass liner group but not in the control group. Brain reward responses to food cues were not different between groups. The number of mean quality-adjusted life-years gained was similar in both groups and the additional costs of the duodenal–jejunal bypass liner may outweigh the value of the health benefits by £2560 per patient treated.ConclusionsThe results show that the endoluminal duodenal–jejunal bypass liner was not superior to intensive medical therapy for glycaemic control and was associated with more adverse events. The duodenal–jejunal bypass liner was associated with significant weight loss and improvement in cardiometabolic parameters at 12 months but not at 24 months. Economic evaluation showed that the bypass liner was not cost-effective for glycaemic control or for weight loss.Trial registrationCurrent Controlled Trials ISRCTN30845205.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnership. This will be published in full inEfficacy and Mechanism Evaluation; Vol. 7, No. 6. See the NIHR Journals Library website for further project information. This study was executed with the support of GI Dynamics Inc. and with the kind support of Nutricia Advanced Medical Nutrition for providing oral nutritional supplements.

149-OR: In Utero Exposure to Gestational Diabetes Mellitus Is Associated with Increased Food Intake and Orbital Frontal Cortex Responses to Food Cues

Children exposed to gestational diabetes mellitus (GDM) in utero have an increased propensity of developing obesity. Little is known about the mechanisms underlying this propensity. Here we examine the relationship between GDM exposure and its timing on energy intake (EI) and brain reward responses to food cues in children. Participants were 142 children (39% boys; 56% GDM-exposed) aged from 7 to 11 years old. GDM status was extracted from EMR. Adiposity measurements were collected. Repeated 24-hour recalls were conducted to assess mean daily EI (kcal/day). A subset (n=89) of children completed an MRI session where they viewed food and non-food cues. %signal change in the orbital frontal cortex (OFC), insula and amygdala for food vs. non-food contrast was measure of interest. GDM exposure was modeled by: 1) yes vs. no at any time in pregnancy and 2) GDM diagnosed at &amp;lt;= 26 weeks (early exposed), &amp;gt; 26 weeks (late exposed) and unexposed. GDM exposure (vs. unexposed) was associated with greater EI (mean difference ±SE: 169 ±65, P=0.01) and OFC food cue reactivity (0.19±0.09, P=0.04). Results were strengthened after adjusting for age, sex, physical activity, SES and pre-pregnancy BMI (EI: P=0.008; OFC: P=0.024). In the adjusted models, both subgroups (early exposed(N=27): 178 ± 92, P=0.055; late exposed (N=53): 173±72, P=0.018) had greater EI than controls. Early exposed group had greater OFC food cue reactivity than controls (0.30±0.15, P=0.048) and the difference between late exposed and controls was marginally significant (0.20±0.11, P=0.07). Children exposed to GDM (vs. unexposed) had larger WHR (0.02±0.01, P=0.03), and this was driven by the difference between early exposed vs. controls (0.04±0.01, P=0.006). Exposure to GDM in utero, in particular before 26 weeks gestation, is associated with increased energy intake, enhanced OFC food cue reactivity and increased WHR. Whether these changes predict development of obesity remains to be determined. Disclosure S.H. Luo: None. B.C. Angelo: None. T. Chow: None. J. Alves: None. T.A. Buchanan: None. A. Xiang: None. K.A. Page: None. Funding National Institutes of Health (K01DK11563)

Food or money? Children's brains respond differently to rewards regardless of weight status.

Brain responses to both food and monetary rewards have been linked to weight gain and obesity in adults, suggesting that general sensitivity to reward contributes to overeating. However, the relationship between brain reward response and body weight in children is unclear. The objective of this study was to assess the brain's response to multiple rewards and the relationship to body weight in children. We tested this by performing functional magnetic resonance imaging while children (7- to 11-years-old; healthy weight [n=31], overweight/obese [n=30]) played a modified card-guessing task to assess blood-oxygen-level-dependent (BOLD) response to anticipating and winning food and money rewards. Functional magnetic resonance imaging data were analysed using a region of interest and exploratory whole-brain approach. Region of interest results demonstrated increased BOLD response in the striatum to anticipating food vs. neutral (control) and winning money vs. neutral. Whole-brain data showed that winning money vs. food was associated with increased activation in the striatum, as well as regions associated with cognitive control and emotion. Notably, for both approaches, these effects were independent of child weight status. Additionally, children's reported food responsiveness and emotional overeating were negatively correlated with the BOLD response in the left cingulate gyrus for winning food vs. money. Overall, findings from this study show that regions associated with reward, cognitive control and emotion may play a role in the brain's response to food and money rewards, independently of how much the child weighs. These findings provide insight into reward sensitivity in children, which may have implications for understanding overeating and the development of obesity.

Association of Brain Reward Learning Response With Harm Avoidance, Weight Gain, and Hypothalamic Effective Connectivity in Adolescent Anorexia Nervosa

Anorexia nervosa (AN) is associated with adolescent onset, severe low body weight, and high mortality as well as high harm avoidance. The brain reward system could have an important role in the perplexing drive for thinness and food avoidance in AN. To test whether brain reward learning response to taste in adolescent AN is altered and associated with treatment response, striatal-hypothalamic connectivity, and elevated harm avoidance. In this cross-sectional multimodal brain imaging study, adolescents and young adults with AN were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classical conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error (PE). Dynamic effective connectivity during sweet taste receipt was studied to investigate hierarchical brain activation across the brain network that regulates eating. The study was conducted from July 2012 to May 2017, and data were analyzed from June 2017 to December 2017. Prediction error brain reward response across the insula, caudate, and orbitofrontal cortex; dynamic effective connectivity between hypothalamus and ventral striatum; and treatment weight gain, harm avoidance scores, and salivary cortisol levels and their correlations with PE brain response. Of 56 female participants with AN included in the study, the mean (SD) age was 16.6 (2.5) years, and the mean (SD) body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 15.9 (0.9); of 52 matched female controls, the mean (SD) age was 16.0 (2.8) years, and the mean (SD) BMI was 20.9 (2.1). Prediction error response was elevated in participants with AN in the caudate head, nucleus accumbens, and insula (multivariate analysis of covariance: Wilks λ, 0.707; P = .02; partial η2 = 0.296), which correlated negatively with sucrose taste pleasantness. Bilateral AN orbitofrontal gyrus rectus PE response was positively correlated with harm avoidance (right ρ, 0.317; 95% CI, 0.091 to 0.539; P < .02; left ρ, 0.336; 95% CI, 0.112 to 0.550; P < .01) but negatively correlated with treatment BMI change (right ρ, -0.282; 95% CI, -0.534 to -0.014; P < .04; left ρ, -0.268; 95% CI, -0.509 to -0.018; P < .045). Participants with AN showed effective connectivity from ventral striatum to hypothalamus, and connectivity strength was positively correlated with insula and orbitofrontal PE response. Right frontal cortex PE response was associated with cortisol, which correlated with body dissatisfaction. These results further support elevated PE signal in AN and suggest a link between PE and elevated harm avoidance, brain connectivity, and weight gain in AN. Prediction error may have a central role in adolescent AN in driving anxiety and ventral striatal-hypothalamus circuit-controlled food avoidance.

Enhancing Natural Reward Responsiveness Among Opioid Users Predicts Chronic Pain Relief: EEG Analyses From a Trial of Mindfulness-Oriented Recovery Enhancement.

Although opioid-treated chronic pain patients evidence blunted responsiveness to natural rewards, focusing on naturally rewarding stimuli can produce analgesia in these patients. A prior randomized controlled trial (RCT) demonstrated that a social work intervention-Mindfulness-Oriented Recovery Enhancement (MORE)-enhanced natural reward processing as indicated by event-related brain potentials (ERPs). The aim of the present study was to perform a secondary data analysis on ERPs collected in this RCT to explore whether improvements in electrocortical response to natural reward predicted pain relief. The sample for this secondary analysis included opioid-treated chronic pain patients with complete ERP data (N = 29). Participants were randomized to 8 weeks of MORE or a support group control condition, and ERPs to images representing naturally rewarding stimuli were measured before and after 8 weeks of treatment. We explored associations between changes in brain reward response, chronic pain symptoms, and pain coping. Increases in ERP reward response were significantly associated with decreased pain severity from pretreatment to posttreatment (β = -.48, p = .007) and improvements in pain catastrophizing (β = -.36, p = .05) and diverting attention as a means of pain coping (β = .38, p = .043). Increased ERP reward response predicted decreased pain interference by 3-month follow-up (β = -.37, p = .048). Chronic pain may be alleviated by enhancing brain response to natural rewards.

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.

Does the Brain's Reward Response Occur Even Without Actual Reward? A Response to Fielding et al. (2017).

A recent paper by Fielding et al. (J Gamb Stud, 2017) argued that the brain's reward response could occur without the presentation of actual reward. We suggest that since (a) the event-related potentials reported in this paper are atypical of the previous literature, and, (b) a simpler account of the data in terms of sensitivity to outcome frequency cannot be ruled out, the extent to which the brain's reward response can occur without the presentation of actual reward should remain an open question.

Brain Reward Responses Are Behaviorally Relevant: The Authors Respond

Brain Reward Responses Are Behaviorally Relevant: The Authors Respond

Brain Reward Responses Are Behaviorally Relevant: The Authors Respond

Brain Reward Responses Are Behaviorally Relevant: The Authors Respond

Brain reward responses to food stimuli among female monozygotic twins discordant for BMI

Obese individuals are characterized by altered brain reward responses to food. Despite the latest discovery of obesity-associated genes, the contribution of environmental and genetic factors to brain reward responsiveness to food remains largely unclear. Sixteen female monozygotic twin pairs with a mean BMI discordance of 3.96 ± 2.1 kg/m2 were selected from the Netherlands Twin Register to undergo functional MRI scanning while watching high- and low-calorie food and non-food pictures and during the anticipation and receipt of chocolate milk. In addition, appetite ratings, eating behavior and food intake were assessed using visual analog scales, validated questionnaires and an ad libitum lunch. In the overall group, visual and taste stimuli elicited significant activation in regions of interest (ROIs) implicated in reward, i.e. amygdala, insula, striatum and orbitofrontal cortex. However, when comparing leaner and heavier co-twins no statistically significant differences in ROI-activations were observed after family wise error correction. Heavier versus leaner co-twins reported higher feelings of hunger (P = 0.02), cravings for sweet food (P = 0.04), body dissatisfaction (P < 0.05) and a trend towards more emotional eating (P = 0.1), whereas caloric intake was not significantly different between groups (P = 0.3). Our results suggest that inherited rather than environmental factors are largely responsible for the obesity-related altered brain responsiveness to food. Future studies should elucidate the genetic variants underlying the susceptibility to reward dysfunction and obesity.Clinical Trial Registration Number: NCT02025595.