Summary Maintaining energy homeostasis is vital and supported by vagal signaling between digestive organs and the brain. Previous research has established a gastric network in the brain that is phase synchronized with the rhythm of the stomach, but tools to perturb its function were lacking. Here, we investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus sham stimulation (randomized crossover-design) on stomach-brain coupling. In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state. Hence, taVNS alters stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, potentially paving the way for novel treatments in disorders such as Parkinson’s disease or depression. Graphical Abstract Highlights Transcutaneous vagus nerve stimulation (taVNS) can emulate interoceptive signals taVNS boosts stomach-brain coupling in the brainstem, midbrain, and transmodal cortex taVNS-induced changes in stomach-brain coupling mirror subjective hunger ratings

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway