Noninvasive Vagus Nerve Stimulation Modulates Pavlovian Bias in a State-Dependent Manner.

OBJECTIVES: The vagus nerve transmits vital signals between organ systems of the body and the brain. Despite growing interest in noninvasive transcutaneous vagus nerve stimulation (tVNS) for treatments of various disorders, it is not known whether its modulatory effects on behavior are dependent on bodily states. MATERIALS AND METHODS: Here, we used a single-blind randomized cross-over design with two within-participant factors, stimulation (right tVNS vs sham) and metabolic state (water vs caloric load), to investigate 54 healthy participants (210 sessions) after an overnight fast. To evaluate state-dependent changes in reinforcement learning, we used a valenced go/no-go task. Performance on this task can be used to estimate a Pavlovian choice bias, which captures improved performance for valence-congruent actions (eg, go to win rewards) vs valence-incongruent actions (eg, no-go to win rewards) and has been associated with dopaminergic neurotransmission. We assessed task-related outcomes using linear mixed-effects models and reinforcement learning models. RESULTS: In line with theorized state-dependency of tVNS-induced changes, we observed that the tVNS effect on Pavlovian response bias depended on the caloric load (Go × Win × Stimulation × Load: p = 0.038), with increases after water and decreases after the milkshake. Considering individual changes in hunger but not satiety ratings best captured behavioral modulation, indicating that this modulatory effect could be driven by motivational effects related to metabolic interoception (sensed "need"). CONCLUSIONS: We conclude that right tVNS decreases Pavlovian response biases if the body is in a postprandial but not a fasting state. Given fasting and Pavlovian biases have been previously associated with elevated dopamine neurotransmission, our results call for additional research on state-dependent motivational effects of tVNS to optimize interventions.