Multimodal Reorganization of Gut--Brain Physiology During the Cephalic Phase of Digestion

The vagus nerve plays a central role in gut--brain communication, yet the physiological dynamics associated with cholinergic vagal signaling remain difficult to characterize non-invasively in humans. The cephalic phase response, which prepares the gastrointestinal system for food ingestion through anticipatory vagal pathways, offers a unique opportunity to investigate these interactions. Here, we used simultaneous recordings of cortical, gastric, cardiac, and swallow physiology in healthy adults to characterize brain--body responses during food anticipation and subsequent ingestion. Food-related sensory cues increased gastric myoelectric activity as well as swallow and heart rate while eliciting frequency-specific changes in cortical oscillations. Strikingly, anticipation was accompanied by opposing changes in physiological coordination: synchronization within cortical and gastric networks decreased, whereas coupling between the brain and stomach increased. These changes largely returned toward baseline following ingestion, suggesting a distinct anticipatory organization of brain--body activity. Moreover, gastric responses were associated with various aspects of subjective appetite, whereas cortical responses were selectively associated with craving. Both gastric and cortical responses independently explained the variation in participants' self-reported craving. Together, these findings reveal that food anticipation reorganizes physiological coordination within and across central and peripheral systems, establishing the cephalic phase as a non-invasive framework for investigating brain--body interactions associated with cholinergic vagal signaling in humans.