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Abstract:
Introduction: Anhedonia is a core symptom in many mental disorders such as major depressive disorder (MDD). Generally defined as the 'inability to experience pleasure', recent debates push towards a conceptual revision emphasizing an understanding of anhedonia as a motivational deficit to work for rewards [1]. Moreover, MDD is associated with changes in body weight, but the underlying mechanisms are not well understood. Vagus nerve stimulation is a promising novel therapy of treatment-resistant MDD [2], as well as treatment-resistant obesity [3]. However, the exact mechanisms behind the treatment effects are largely unknown. Intriguingly, emerging evidence suggests that the vagus nerve affects dopaminergic circuits and metabolic signaling [4]. Therefore, we expected non-invasive transcutaneous vagus nerve stimulation (tVNS) to enhance the motivation to exert effort for rewards by modulating the effect of costs and benefits on instrumental behavior.
Methods: We applied tVNS/sham stimulation in a randomized crossover design to healthy normal- to overweight participants (N=24) after an overnight fast. As part of an ongoing study, they completed two morning sessions of a modified effort allocation task (EAT) [5]. Participants had to maintain a varying proportion of their individual maximum button press frequency in order to gain monetary and food rewards. The task comprises of 48 trials, in which we manipulated the reward magnitude, type and the difficulty to obtain the reward. We performed hierarchical linear regression analyses as implemented in HLM7 to investigate the impact of the stimulation on the invigoration and maintenance of behavior.
Results: We found that the EAT tracks important aspects of costs and benefits of action as reflected in significant effects of reward magnitude, t(23)=3.310, p=0.003, and task difficulty, t(23)= -2.721, p=0.012, on average button press frequency. Moreover, we found that higher reward magnitude increased effort invigoration by 8%, t(23)=4.131, p<0.001. Critically, the stimulation increased the invigoration by an additional 6% relative to baseline, t(22)=3.042, p=0.006, but did not have a significant impact on the maintenance of behavior, t(22)=0.274, p=0.787, even if maintenance was corrected for day-to-day differences in baseline performance, t(23)=1.60, p=0.124.
Discussion: Our findings confirm the suitability of the EAT to study effort-based decision-making over time. We found that effort invigoration, but not maintenance was facilitated by tVNS. Notably, the effect of stimulation on invigoration is almost as strong as the drive elicited by a tenfold increase of the reward magnitude at stake. Nevertheless, more data is needed to assess whether the absence of tVNS effects on effort maintenance is partly due to a carry-over effect. To conclude, the preliminary results point towards an influence of tVNS on dopaminergic signaling. Therefore, anti-depressant and weight-loss effects of the stimulation could be explained by an enhanced incentive value conferred by rewards.
