ANCILLARY PROJECT 2 Abstract: Effect of VNS on Gastric Motor Functions The prevalence of gastroparesis (i.e., inability for the stomach to empty itself normally) ranges from 13.8 to 267.7 per 100,000 adults; in addition, 2.5% are hospitalized each year, with 0.3% mortality. There is no consistently effective treatment for this condition: the only FDA-approved medication, metoclopramide, can only be used for <12 weeks because of risk of the debilitating movement disorder tardive dyskinesia. To gather key data as a foundation for new gastroparesis treatment, we propose to evaluate the effect of left vagus nerve stimulation (VNS) on gastric emptying and accommodation functions in patients undergoing treatment for depression or epilepsy. Whereas the effects of VNS on other functions such as sleep patterns or heart period responses reflecting cardiovagal innervation have been reported, the effects of such treatment on gastric functions are unknown. It is clear, however, that the vagus nerve provides the extrinsic input to cholinergic intrinsic neurons that stimulate gastric muscle contractility and to the nitrogen-intrinsic neurons that mediate gastric accommodation. Our hypothesis is that cervical VNS increases gastric accommodation and accelerates gastric emptying. Our specific aim is to compare simultaneous assessment of gastric emptying and gastric accommodation in response to the same caloric meal before and three months after activation of left cervical VNS. The functions of the stomach will be measured using validated methods conducted simultaneously using SPECT camera imaging and a radiolabeled meal, with a first measurement of gastric volume during fasting after intravenous injection of pertechnetate and a second measurement of postprandial gastric volume accommodation and gastric emptying following the ingestion of a 320 kilocalorie, 30% fat egg meal. These innovative studies will document the effect of VNS as the foundation for a potential novel treatment for correcting disorders of gastric motor function.