Direct measurement of vagal tone in rats does not show correlation to HRV Author: Joseph T Marmerstein1, Grant A McCallum1, Dominique M Durand2 Affiliation: <sup>1</sup> Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. <sup>2</sup> Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA. dxd6@case.edu. Conference/Journal: Sci Rep Date published: 2021 Jan 13 Other: Volume ID: 11 , Issue ID: 1 , Pages: 1210 , Special Notes: doi: 10.1038/s41598-020-79808-8. , Word Count: 175 The vagus nerve is the largest autonomic nerve, innervating nearly every organ in the body. "Vagal tone" is a clinical measure believed to indicate overall levels of vagal activity, but is measured indirectly through the heart rate variability (HRV). Abnormal HRV has been associated with many severe conditions such as diabetes, heart failure, and hypertension. However, vagal tone has never been directly measured, leading to disagreements in its interpretation and influencing the effectiveness of vagal therapies. Using custom carbon nanotube yarn electrodes, we were able to chronically record neural activity from the left cervical vagus in both anesthetized and non-anesthetized rats. Here we show that tonic vagal activity does not correlate with common HRV metrics with or without anesthesia. Although we found that average vagal activity is increased during inspiration compared to expiration, this respiratory-linked signal was not correlated with HRV either. These results represent a clear advance in neural recording technology but also point to the need for a re-interpretation of the link between HRV and "vagal tone". PMID: 33441733 DOI: 10.1038/s41598-020-79808-8