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Item An emerging method to noninvasively measure and identify vagal response markers to enable bioelectronic control of gastroparesis symptoms with gastric electrical stimulation(Elsevier, 2020-04-15) Ward, Matthew P.; Gupta, Anita; Wo, John M.; Rajwa, Bartek; Furness, John B.; Powley, Terry L.; Nowak, Thomas V.; Medicine, School of MedicineBackground: Gastric electrical stimulation (GES) can be a life-changing, device-based treatment option for drug-resistant nausea and vomiting associated with diabetic or idiopathic gastroparesis (GP). Despite over two decades of clinical use, the mechanism of action remains unclear. We hypothesize a vagal mechanism. New method: Here, we describe a noninvasive method to investigate vagal nerve involvement in GES therapy in 66 human subjects through the compound nerve action potential (CNAP). Results: Of the 66 subjects, 28 had diabetic GP, 35 had idiopathic GP, and 3 had postsurgical GP. Stimulus charge per pulse did not predict treatment efficacy, but did predict a significant increase in total symptom score in type 1 diabetics as GES stimulus charge per pulse increased (p < 0.01), representing a notable side effect and providing a method to identify it. In contrast, the number of significant left and right vagal fiber responses that were recorded directly related to patient symptom improvement. Increased vagal responses correlated with significant decreases in total symptom score (p < 0.05). Comparison with existing method(s): We have developed transcutaneous recording of cervical vagal activity that is synchronized with GES in conscious human subjects, along with methods of discriminating the activity of different nerve fiber groups with respect to conduction speed and treatment response. Conclusions: Cutaneous vagal CNAP analysis is a useful technique to unmask relationships among GES parameters, vagal recruitment, efficacy and side-effect management. Our results suggest that CNAP-guided GES optimization will provide the most benefit to patients with idiopathic and type 1 diabetic gastroparesis.