Eye blink and reward prediction error response in anorexia nervosa.

BACKGROUND: Functional brain imaging has been used to study brain reward function and behavioral traits in anorexia nervosa (AN). Here we tested whether eye blink relates to behavior and brain imaging response as a method that is less costly and more accessible. METHOD: We recruited 26 women with AN and 50 healthy matched controls. All underwent a reward-learning prediction error task during functional magnetic resonance imaging. In addition, eye blink was measured for spontaneous blink rate, baseline blink amplitude, and startle response to an auditory stimulus. RESULTS: Baseline blink rate, amplitude and startle response were similar between groups. In AN, there were significant positive correlations between spontaneous blink rate and bulimia symptoms, and baseline blink amplitude and prediction error response in right-sided caudate, insula, and nucleus accumbens. Correlations between eye blink measures and body dissatisfaction or harm avoidance were no longer significant after multiple comparison adjustments. DISCUSSION: This study provides evidence that measures of eye blink response can be related to brain prediction error response and eating disorder behavior in AN. The catecholamine dopamine contributes to both eye blink and prediction error response providing indirect evidence that it could be a neurobiological correlate that contributes to behaviors relevant to AN.

The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa.

OBJECTIVE: Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience-based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine-related reward circuits are hypersensitive and could provide a treatment target. METHODS: Here, we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program. RESULTS: The results show that aripiprazole treatment was associated with greater increase in body mass index (BMI) during treatment. DISCUSSION: The use of dopamine receptor agonists may support treatment success in anorexia nervosa and should be further investigated.

The Neurobiology of Eating Disorders.

Eating disorders are severe psychiatric illnesses with a typical age of onset in adolescence. Brain research in youth and young adults may help us identify specific neurobiology that contributes to onset and maintenance of those disorders. This article provides a state-of-the-art review of our current understanding of the neurobiology of anorexia nervosa and bulimia nervosa. This includes brain structure and function studies to understand food restriction, binge-eating or purging behaviors, cognitive and emotional factors, as well as interoception. Binge-eating disorder and avoidant restrictive food intake disorder are also discussed, but the literature is still very small.

Recent advances in understanding anorexia nervosa.

Anorexia nervosa is a complex psychiatric illness associated with food restriction and high mortality. Recent brain research in adolescents and adults with anorexia nervosa has used larger sample sizes compared with earlier studies and tasks that test specific brain circuits. Those studies have produced more robust results and advanced our knowledge of underlying biological mechanisms that may contribute to the development and maintenance of anorexia nervosa. It is now recognized that malnutrition and dehydration lead to dynamic changes in brain structure across the brain, which normalize with weight restoration. Some structural alterations could be trait factors but require replication. Functional brain imaging and behavioral studies have implicated learning-related brain circuits that may contribute to food restriction in anorexia nervosa. Most notably, those circuits involve striatal, insular, and frontal cortical regions that drive learning from reward and punishment, as well as habit learning. Disturbances in those circuits may lead to a vicious cycle that hampers recovery. Other studies have started to explore the neurobiology of interoception or social interaction and whether the connectivity between brain regions is altered in anorexia nervosa. All together, these studies build upon earlier research that indicated neurotransmitter abnormalities in anorexia nervosa and help us develop models of a distinct neurobiology that underlies anorexia nervosa.

Motivation to eat and not to eat - The psycho-biological conflict in anorexia nervosa.

Anorexia nervosa is a severe psychiatric illness with high mortality. Brain imaging research has indicated altered reward circuits in the disorder. Here we propose a disease model for anorexia nervosa, supported by recent studies, that integrates psychological and biological factors. In that model, we propose that there is a conflict between the conscious motivation to restrict food, and a body-homeostasis driven motivation to approach food in response to weight loss. These opposing motivations trigger anxiety, which maintains the vicious cycle of ongoing energy restriction and weight loss.

Neural correlates of taste reward value across eating disorders.

Individuals with eating disorders (ED) make extreme food choices, raising the possibility of altered food-value computation. We utilized an associative taste reward learning paradigm to test whether value signaling differs between participants with EDs vs. healthy controls (HC). We followed up on previous work examining prediction error (PE) signaling, which is a brain response to violation of a learned reward contingency. Expected value (EV) signal is a trial-by-trial assessment of reward significance accounting for error signaling, reward-likelihood, and learning rate. Adult female participants (N = 111) performed a temporal difference (TD) fMRI taste task, which is a specific type of associative reward learning paradigm, to determine EV signal: Anorexia Nervosa-ill (N = 28), Anorexia Nervosa-recovered (N = 20), Bulimia Nervosa (BN) (N = 20), and HC (N= 43). Anatomical region-of-interest (ROI) analyses were performed utilizing EV regressors derived via algorithm, with ROIs based on prior EV analyses: orbitofrontal cortex, anterior cingulate (ACC), amygdala, and striatum. EV signal was elevated in the bilateral ACC in AN-ill vs. HC and BN. Intolerance of uncertainty negatively correlated with EV in AN-ill. BMI and EV were negatively-correlated across groups. Altered ACC EV computation in response to food stimuli could contribute to food restriction in AN-ill.

Dopamine D2 -141C Ins/Del and Taq1A polymorphisms, body mass index, and prediction error brain response.

The prediction error model is a widely used paradigm that is conceptually based on neuronal dopamine function. However, whether dopamine receptor gene alleles contribute to human neuroimaging prediction error results is uncertain. Recent research implicated the dopamine D2 receptor in behavior response during a prediction error paradigm and we expected that polymorphisms of that receptor would contribute to prediction error brain response. In this study, healthy female participants in the early follicular phase of the menstrual cycle underwent a taste prediction error paradigm during functional magnetic resonance imaging. Participants were also genotyped for dopamine receptor polymorphisms. Our data suggest that the dopamine D2 receptor -141C Ins/Del and Taq1A polymorphisms together with body mass index selectively explain putamen prediction error response. This was true using a region of interest analysis as well as for a whole-brain analysis (FWE corrected). Polymorphisms for dopamine D1 or D4 receptors, dopamine transporter, or COMT did not significantly contribute to prediction error activation. The prediction error model is a computational reward-learning paradigm that is important in psychiatric research and has been associated with dopamine. The results from this study indicate that dopamine D2 receptor polymorphisms together with body mass index are important determinants to include in research that tests prediction error response of the brain. Psychiatric disorders are frequently associated with elevated or reduced body weight. Adding BMI to genetic information in brain-imaging studies that use reward and the prediction error paradigm may be important to increase validity and reliability of results.

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

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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. Conclusions and Relevance: 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.