To study the impact of tVNS on gut motor function, with regards to its potential to induce phase III contractions in the upper GI tract, in healthy subjects.

Hypothesis: We hypothesize that tVNS will induce on average an excess of 1 additional phase III contraction of antral origin in the fasted period compared to sham stimulation.

Healthy volunteers (n=12) will be recruited, both male and female, aged aged 18-55 years old. Participants will arrive after an overnight fast at the GI physiology unit ('functiekamer') of the Maastricht University Medical Center, where they will be inserted an antroduodenal manometry catheter through the nose into the duodenum under fluoroscopy control. The high-resolution catheter contains 36 transducers spaced at 1-cm intervals (Unisensor AG, Attikon, Switzerland). Using this catheter, stomach and duodenum motility patterns will be recorded for 8 hours.

Participants will undergo tVNS (cymba concha of the left ear) alternated with sham (a non-conducting electrode) in a blinded pre-randomized fashion using 2 blocks of 4 hours during the 8-hour registration period. In addition, blood samples will be taken at baseline and at intervals of 30 minutes during the 8-hour test period. Levels of the GI hormones motilin and PP will be measured as surrogate markers of vagal efferent influence on GI motor function.

Autonomic parameters will be registered using pulse plethysmography. A wearable device (Shimmer3 GSR Sensor) will also be used to measure heart rate variability and skin conductance. Heart rate variability is regarded as a parameter reflecting cardiac parasympathetic activity.(33, 34) The root mean square of successive differences (RMSSD) is a commonly utilized and thoroughly validated measure of heart (and pulse) rate variability. (35, 36).

After the 8-hour registration period, all measurement equipment and the iv. cannula is removed. Participants are provided a meal voucher to be consumed at the hospital visitor's restaurant, whereafter the test day is finished.

Inclusion Criteria:

• Healthy participants (defined as those without a pre-existing medical comorbidity, including those without a history of cardiac arrhythmia).
• Age between 18 and 55 years.
• Ability to understand and speak the Dutch language.

Exclusion Criteria:

• Pregnancy or lactation.
• Use of any substances (such as medication or recreational drugs) influencing gastrointestinal motility
• Not meeting the inclusion criteria above.
• Students and employees of Maastricht University are not precluded from participation, unless they have a direct personal, professional of hierarchical position with regards to any of the study team members or their department.

Participant and investigator will not know the randomization order of tVNS