Mesolimbic Neurobehavioral Mechanisms of Reward Motivation in Anorexia Nervosa: A Multimodal Imaging Study

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.

White matter microstructure in habit and reward circuits in anorexia nervosa: Insights from a neurite orientation dispersion and density imaging study

“…One speculation is that the set of findings in the AN group of less dense, under‐myelinated, and less dispersed VTA‐NAcc tracts might signify underutilization of this part of the reward circuit. This is supported by a previous analysis in the same sample of AN participants who engaged in a reward fMRI task, in which we observed reduced functional connectivity in VTA‐NAcc and delayed response times for reward motivation—evidence for lower activity in this circuit 26 . Further, in the current study, those with lower orientation dispersion in the VTA‐NAcc—“straighter” fiber tracts—had lower BAS reward responsiveness.…”

“…Our group's recent seed-to-seed tractography analyses of white matter tracts between sensory motor area (SMA) to putamen, a circuit known to be implicated in habitual decision-making (25), found that the volume of tracts in this circuit were associated with the severity of ritualized behaviors (25). A separate study revealed delayed response time in adolescents with AN when anticipating potential rewards (26).…”

“… 25 A separate study revealed delayed response time in adolescents with AN when anticipating potential rewards. 26 Also in that study, probabilistic tractography illustrated reduced integrity in white matter tracts connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAcc)—a major mesolimbic dopaminergic projections pathway implicated in reward. As well, there was reduced VTA‐NAc functional connectivity in those with AN.…”

“…Our group's recent seed‐to‐seed tractography analyses of white matter tracts between sensory motor area (SMA) to putamen, a circuit known to be implicated in habitual decision‐making, 25 found that the volume of tracts in this circuit were associated with the severity of ritualized behaviors 25 . A separate study revealed delayed response time in adolescents with AN when anticipating potential rewards 26 . Also in that study, probabilistic tractography illustrated reduced integrity in white matter tracts connecting the ventral tegmental area (VTA) and the nucleus accumbens (NAcc)—a major mesolimbic dopaminergic projections pathway implicated in reward.…”

Multicomponential affective processes modulating food-seeking behaviors

“…a lack of experienced pleasure) symptoms, reflecting an imbalance between impaired, hypoactive motivational processes and intact hedonic processes [37]. Such diminished motivational processes in reward processing have also been observed in eating disorders such as anorexia nervosa [40].…”