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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Frank reported grants from National Institute of Mental Health Grant for the study, no conflict of interest during the conduct of the study. Dr Stoddard reported grants from NIMH RO1MH103436 and grants from NIMH K23MH113731 during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Effective Connectivity Maps Across Study Groups

The yellow arrow indicates effective dynamic connectivity in opposite directions between ventral striatum and hypothalamus. ACC, anterior cingulate cortex; BA/BLA, basolateral amygdala; CAN, central nucleus of the amygdala; HYP, hypothalamus; L, left; OFC, orbitofrontal cortex; PFC, prefrontal cortex; R, right; SN, substantia nigra; VMP, ventral midbrain/pons.

Figure 2.. Model for Interaction Between Behaviors, Body Mass Index, and Brain Function

The solid lines indicate proposed mechanistic relationships; the broken lines indicate indirect associations. Numeric values report Pearson correlation values. BDI indicates Beck Depression Inventory 2; BMI, body mass index; EDI, Eating Disorder Inventory-3; EEI, Eating Expectancy Inventory; IUS, Intolerance of Uncertainty Scale; PE, prediction error; Sensitivity to Punishment and Sensitivity to Reward Questionnaire; SP, Sensitivity to Punishment subscale; TCI indicates Temperament and Character Inventory–novelty seeking; VS, ventral striatum. aP < .001. bP < .01. Specific values available in eTable 2 in the Supplement. cP < .05. Specific values available in eTable 2 in the Supplement.