Direct measurement of vagal tone in rats does not show correlation to HRV

Abstract

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”.

Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases

“…One can imagine that, an indicator such as HRV, easy to assess through the detection of heartbeat intervals, could be used to explore the microbiota-gut-brain axis homeostasis. Indeed, HRV is probably not a direct index of "the true" vagal tone (Marmerstein et al, 2021) since it is an indirect assessment of the parasympathetic modulation on the heart so that the metrics of the HRV would rather reflect different aspects of the neurophysiologic regulation of the heart rhythm (Reyes del Paso et al, 2013;Thomas et al, 2019). Presently, HRV is the final output of several regulatory loops resulting from afferent signals integrated at the level of the CNS influencing the efferent vagally mediated modulations on the heart (Thayer and Lane, 2009).…”

Auricular Vagus Neuromodulation—A Systematic Review on Quality of Evidence and Clinical Effects

“…More variance in HR during breathing indicates more vagal control and a corresponding shift in cardiac sympathovagal balance to parasympathetic (Goldberger, 1999). Contradictory results on the parasympathetic effects of aVNS indicates that either the effects of aVNS on HRV are inconsistent, or that HRV is an unreliable measure of cardiac sympathovagal balance (Bootsma et al, 2003;Billman, 2013;Hayano and Yuda, 2019;Marmerstein et al, 2021), or both. Overall, the effects of aVNS on sympathovagal balance conflict between studies.…”

The Heart in the Mind: A Systematic Review and Meta-Analysis of the Association Between Theory of Mind and Cardiac Vagal Tone

“…Meanwhile, the results from several meta-analytic works suggested that vagal control is positively associated with social functioning (Shahrestani et al, 2014(Shahrestani et al, , 2015 and positive effect (Di Bello et al, 2020), as well as negatively correlated with psychopathological symptoms and conditions (e.g., Chalmers et al, 2014;Ottaviani et al, 2016;Koch et al, 2019). More recently, Marmerstein et al (2021) have questioned the link between vagal modulation and HRV, showing a lack of association between HRV measures (e.g., RMSSD, HF-HRV, and LF-HRV) and tonic vagal activity assessed in the left cervical vagus and with a respiratory vagal difference in rats with and without anesthesia. Conversely, other researchers have asserted that HF-HRV and other time-domain metrics (e.g., RMSSD) constitute a good measure of vagal activity in humans, as suggested by a seminal preclinical study on this topic (Ter Horst and Postema, 1997).…”