Abstract
Diminished motivation to pursue and obtain primary and secondary rewards has been demonstrated in anorexia nervosa (AN). However, the neurobehavioral mechanisms underlying the behavioral activation component of aberrant reward motivation remains incompletely understood. This work aims to explore this underexplored facet of reward motivation in AN. We recruited female adolescents with AN, restricting type (n = 32) and a healthy control group (n = 28). All participants underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. Diffusion MRI data was also collected to examine the reward motivation circuit's structural connectivity. Behavioral results demonstrated slower speed of reward-seeking behavior in those with AN compared with controls. Accompanying this was lower functional connectivity and reduced white matter structural integrity of the connection between the ventral tegmental area/substantia nigra pars compacta and the nucleus accumbens within the mesolimbic circuit. Further, there was evidence of neurobehavioral decoupling in AN between reward-seeking behavior and mesolimbic regional activation and functional connectivity. Aberrant activity of the bed nucleus of the stria terminalis (BNST) and its connectivity with the mesolimbic system was also evident in AN during the reward motivation period. Our findings suggest functional and structural dysconnectivity within a mesolimbic reward circuit, neurofunctional decoupling from reward-seeking behavior, and abnormal BNST function and circuit interaction with the mesolimbic system. These results show behavioral indicators of aberrant reward motivation in AN, particularly in its activational component. This is mediated neuronally by mesolimbic reward circuit functional and structural dysconnectivity as well as neurobehavioral decoupling. Based on these findings, we suggest a novel circuit-based mechanism of impaired reward processing in AN, with the potential for translation to developing more targeted and effective treatments in this difficult-to-treat psychiatric condition.
Highlights
Anorexia nervosa (AN) has one of the highest mortality rates among all mental illnesses [1]
Participants with AN had significantly lower BMI compared to controls (BMI percentile: AN group = 26.0 ± 17.2, control group = 66.4 ± 21.0, t = 7.93 P < 0.0001; raw BMI: AN group = 18.2 ± 1.39, control group = 22.3 ± 1.40, t = 8.80, P < 0.0001) as well as significantly higher eating disorder symptom severity determined by YBCEDS and Eating Disorder Examination (EDE) scores
We found that the connectivity of right VTA\SNc-to-sphere seed during the reward motivation period was significantly lower in the AN group compared to controls (HC = 0.21 ± 0.42, AN = −0.002 ± 0.25, F = 5.021, p = 0.03, 95% CI: −0.477 to −0.026, observed power = 0.59, ANCOVA controlling for age, Pubertal Development Scale (PDS) score and anxiety level after scan, Figure 3B) but showed no significant association with BMI value
Summary
Anorexia nervosa (AN) has one of the highest mortality rates among all mental illnesses [1]. Classified as an eating disorder, AN is characterized by self-imposed starvation, physical emaciation, an intense fear of weight gain, and a profound disturbance in the way one’s shape and weight is experienced [2]. One of the putative disease mechanisms in AN is impairment in reward processing. Disturbances in the experience of reward are evident for rewards related to food and eating but extend to other types of reward such as sex and social rewards [3–5]. Even premorbidly, diminished novelty seeking has been observed [6], raising the possibility of phenotypic reward-related abnormalities as potential contributors to the development of the disorder. In affected individual with AN, aberrant processing of rewards could manifest as the appearance of an anhedonic state [7–9]
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