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. 2020 Jun 8;10:9221. doi: 10.1038/s41598-020-66332-y

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Afferent and efferent physiological responses to VNS of opposite polarities. (a) Afferent (breathing rate, BR) and efferent (heart rate, HR) responses to individual VNS trains of stimuli of 2 opposite polarities: cathode cephalad (blue trace), followed by cathode caudad (red trace). Cathode cephalad polarity was associated with a stronger afferent response (−58% change in BR and −14% change in HR), whereas cathode caudad with a stronger efferent response (−20% change in BR and −30% in HR). Stimulation parameters for both trains: 200 μA, 500 μs, 10 s-long train (300 pulses), 30 Hz. (b) Example of BR responses (top panel) and HR responses (bottom panel) to VNS of 2 opposite polarities, at a range of current intensities. Current intensity was normalized with respect to “physiological threshold” (T). In this case, cathode caudad polarity typically elicited greater drops in BR, whereas cathode cephalad greater drops in HR. Each of the 2 two-headed arrows denotes the difference in the corresponding physiological response between the 2 polarities at an intensity level of 6xT: response to cathode caudad minus response to cathode cephalad.