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Introduction: The vagus nerve plays a prominent role in the regulation of food reward and energy metabolism. However, previous studies using vagus nerve stimulation yielded conflicting results regarding changes in food reward in healthy participants and participants with major depressive disorder (MDD), for which vagal nerve stimulation is an effective treatment. Methods: We investigated the acute effects of right transcutaneous auricular vagus nerve stimulation (taVNS) on ratings of liking and wanting of food and non-food items in 63 participants, including 31 patients with MDD. To test for taVNS-induced changes and interactions with between-subject variables group (MDD vs. healthy controls) and questionnaire scores as well as within-subject variables, we performed linear mixed-effects analysis. In addition, we assessed whether individual taVNS-induced changes in food reward ratings were dependent on average ratings.Results: taVNS increased liking of food cues in participants with MDD (p= 0.023), but not in healthy participants (p= 0.657). Specifically, taVNS induced larger improvements in liking ratings with increasing scores of anhedonia (p= 0.029). Notably, across all participants, taVNS reduced the variance of food liking compared to sham, suggesting that taVNS normalizes extreme liking ratings towards moderate levels (p = 0.039).Discussion: Our results show that taVNS acutely ameliorates hedonic responses in MDD suggesting that it could provide an effective treatment of anhedonia. Since anhedonia is difficult to treat with conventional therapies, taVNS may provide a powerful adjuvant to rapidly improve motivational deficiencies.

The vagus nerve plays a vital role in the regulation of food intake and vagal afferent signals may help regulate food cue reactivity by providing negative homeostatic feedback. Despite strong evidence from preclinical studies on vagal afferent ″satiety″ signals in guiding food intake, evidence from human studies is largely inconclusive to date. Here, we investigated the acute effects of left or right transcutaneous auricular vagus nerve stimulation (taVNS) on subjective ratings of wanting and liking of various food and non-food items in 82 healthy participants (46 women, MBMI = 23.1 kg/m2). In contrast to previous reports in patients with depression, we found moderate to anecdotal evidence supporting the absence of taVNS-induced changes in food ratings. To test whether the absence of taVNS effects on food ratings is due to heterogeneity in the sample, we conducted post hoc subgroup analyses by splitting the data according to stimulation side and sex (between-subject factors) as well as caloric density, perceived healthiness, and flavor (sweet vs. savory) of the food (within-subject factors). This multiverse analysis largely supported the absence of taVNS-induced changes since the strongest subgroup effects provided only anecdotal evidence in favor of taVNS-induced changes. We conclude that acute taVNS only has a marginal effect on subjective ratings of food, suggesting that it is an unlikely mechanism for the reported long-term effects of VNS on body weight. In light of an absence of acute taVNS effects on food craving, our results call for future research on the correspondence between acute and chronic effects of vagal afferent stimulation.

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