Mesolimbic Neurobehavioral Mechanisms of Reward Motivation in Anorexia Nervosa: A Multimodal Imaging Study
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.
Additional Information© 2022 Tadayonnejad, Majid, Tsolaki, Rane, Wang, Moody, Pauli, Pouratian, Bari, Murray, O'Doherty and Feusner. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 31 October 2021; Accepted: 10 February 2022; Published: 07 March 2022. This work was supported by National Institute of Mental Health (JDF R01MH093535). RT research was supported by National Institute of Mental Health (K23MH116117 and R01MH121089) and Brain & Behavior Research Foundation (NARSAD-27111). Author Contributions. RT, JO'D, and JF contributed to the conception and design of the work. RT, D-AM, ET, RR, HW, TM, and WP contributed to the data analysis. RT, NP, AB, SM, JO'D, and JF contributed to the interpretation of the results. RT wrote the main manuscript text. All authors reviewed the manuscript. Data Availability Statement. The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. Ethics Statement. The studies involving human participants were reviewed and approved by UCLA IRB. The patients/participants provided their written informed consent to participate in this study. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Published - fpsyt-13-806327.pdf