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

BACKGROUND: Adolescence 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. METHODS: A 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. RESULTS: Adolescents 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. CONCLUSIONS: Associations 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.

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

Importance: Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking. Objective: 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. Design, Setting, and Participants: 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. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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.

Understanding Neuronal Architecture in Obesity through Analysis of White Matter Connection Strength.

Despite the prevalence of obesity, our understanding of its neurobiological underpinnings is insufficient. Diffusion weighted imaging and calculation of white matter connection strength are methods to describe the architecture of anatomical white matter tracts. This study is aimed to characterize white matter architecture within taste-reward circuitry in a population of obese individuals. Obese (n = 18, age = 28.7 ± 8.3 years) and healthy control (n = 24, age = 27.4 ± 6.3 years) women underwent diffusion weighted imaging. Using probabilistic fiber tractography (FSL PROBTRACKX2 toolbox) we calculated connection strength within 138 anatomical white matter tracts. Obese women (OB) displayed lower and greater connectivity within taste-reward circuitry compared to controls (Wilks' λ < 0.001; p < 0.001). Connectivity was lower in white matter tracts connecting insula, amygdala, prefrontal cortex (PFC), orbitofrontal cortex (OFC) and striatum. Connectivity was greater between the amygdala and anterior cingulate cortex (ACC). This study indicates that lower white matter connectivity within white matter tracts of insula-fronto-striatal taste-reward circuitry are associated with obesity as well as greater connectivity within white matter tracts connecting the amygdala and ACC. The specificity of regions suggests sensory integration and reward processing are key associations that are altered in and might contribute to obesity.

Greater Insula White Matter Fiber Connectivity in Women Recovered from Anorexia Nervosa.

Anorexia nervosa is a severe psychiatric disorder associated with reduced drive to eat. Altered taste-reward circuit white matter fiber organization in anorexia nervosa after recovery could indicate a biological marker that alters the normal motivation to eat. Women recovered from restricting-type anorexia (Recovered AN, n = 24, age = 30.3 ± 8.1 years) and healthy controls (n = 24, age = 27.4 ± 6.3 years) underwent diffusion weighted imaging of the brain. Probabilistic tractography analyses calculated brain white matter connectivity (streamlines) as an estimate of fiber connections in taste-reward-related white matter tracts, and microstructural integrity (fractional anisotropy, FA) was assessed using tract-based spatial statistics. Recovered AN showed significantly (range P<0.05-0.001, Bonferroni corrected) greater white matter connectivity between bilateral insula regions and ventral striatum, left insula and middle orbitofrontal cortex (OFC), and right insula projecting to gyrus rectus and medial OFC. Duration of illness predicted connectivity of tracts projecting from the insula to ventral striatum and OFC. Microstructural integrity was lower in Recovered AN in most insula white matter tracts, as was whole-brain FA in parts of the anterior corona radiata, external capsule, and cerebellum (P<0.05, family-wise error-corrected). This study indicates higher structural white matter connectivity, an estimate of fibers connections, in anorexia after recovery in tracts that connect taste-reward processing regions. Greater connectivity together with less-fiber integrity could indicate altered neural activity between those regions, which could interfere with normal food-reward circuit function. Correlations between connectivity and illness duration suggest that connectivity could be a marker for illness severity. Whether greater connectivity can predict prognosis of the disorder requires further study.