How far have we reached? Perhaps not enough, new avenues are about to be travelled

The autonomic nervous system precisely regulates a tissue's function through two crucial branches, the sympathetic and the parasympathetic systems, with both systems providing nervous input to the autonomic nervous system. A classical explanation of the differences in the functionality of both systems is that the sympathetic nervous system is associated with stressful situations, and thus is referred to as the ‘fight-or-flight’ system. By contrast, the parasympathetic nervous system is predominant during rest and is therefore referred to as the ‘rest and digest’ system. The vagus nerve is conventionally associated with the parasympathetic system. The vagus nerve presents sensory and motor functions and its cardiovascular efferent fibres can modulate the myocardium frequency response. However, the direct measure of the parasympathetic nervous system activity in humans has until now not been possible. In a breakthrough study reported in The Journal of Physiology, Ottaviani et al. (2020) successfully recorded vagus nerve activity in awake humans using an ultrasound-guided microneurography approach. For the first time in humans, a tungsten microelectrode was inserted into the vagus nerve in the neck, enabling direct measurement of vagal axon activity. In three of four participants, multi-unit nerve activity was recorded on both sides of the neck, whereas, in only two of the participants, a single-unit recording was obtained. The results showed that the vagal axon activity recorded in all attempts displayed a correlation with either the cardiac or the respiratory cycle. Ottaviani et al. (2020) also recorded what was classified as the cardioinhibitory motor axon (once the Hz range matched that found in animal studies), which showed an inverse relationship with heart rate. Sixty decades ago, Vallbo and Hagbarth developed a technique that consists of inserting a needle into an accessible human nerve to record its action potentials: the ‘simple but not simple’ microneurography technique had emerged. With the advent of this technique that enabled the quantification of sympathetic outflow to skeletal muscles and the skin, impressive discoveries were made that contributed towards a better understanding of the functions of the autonomic nervous system and its many roles in the maintenance of homeostasis (Vallbo et al. 2004). The use of microneurography has been mainly directed towards comprehending the sympathetic nervous system and its relationship with the cardiovascular and haemodynamics systems during rest, as well as during various sympathetic stimuli such as exercise. During acute exercise, the peroneal nerve has often been the sympathetic nerve of choice for insertion of a tungsten electrode when aiming to investigate sympathetic nerve activity (Macefield, 2013). Acute exercise evokes increases in sympathetic nerve activity, leading to notable cardiovascular adjustments, which are of imperative importance for the maintenance of continuous oxygen delivery to skeletal muscle to support increased metabolic demand. In the central point of these cardiovascular adjustments is the heart, an organ presenting a sympathetic and parasympathetic innervation. The initial increases in heart rate during exercise are mainly the result of a withdrawal of cardiac vagal tone, and the subsequent increases in heart rate are intensified by the sympathetic nervous system activation. In addition, not only is heart function altered during an acute bout of exercise, but also the practice of regular exercise induces autonomic changes, strengthening cardiac vagal control during resting periods and accelerating heart recovery after exercise cessation. Until now, our understanding of the cardiac vagal tone contributions in humans has been mainly quantified through several mathematical models that calculate the variability of the heart rate or baroreflex sensitivity as an index of cardiac vagal control (Coote & Bothams, 2001). Reduced heart rate variability and decreased baroreflex sensitivity are indicators of impaired cardiac vagal control that directly relate to increased mortality risk and cardiovascular disease. Besides having great potential in clinical settings, the innovative use of microneurography to directly measure the vagus nerve is an essential step towards our further understanding of the contribution of cardiac vagal tone before, during and after exercise. However, similar to the muscle sympathetic nerve activity (MSNA) technique, which is the standard interpretation of a burst corresponding to a vasoconstriction response and its relationship with cardiac heart rate, there is a challenge with respect to defining what is normal and/or abnormal as a result of considerable variation between individuals. Therefore, there is no doubt that there is much work still to be done to refine the technique, although the work by Ottaviani et al. (2020) has made it possible to envision the future and the vast possibility of direct vagus nerve measurement. With this new direct vagus nerve measurement, a whole new range of studies has become accessible to researchers. These studies could, for example, look into vagal responses during the onset of exercise, as well as investigate the cardiac ‘autonomic conflict’ occurring with simultaneous activation of the sympathetic and parasympathetic system, as seen during diving (Al-Ani et al. 1995). Also, why not expect a simultaneous direct measurement of the vagus nerve and MSNA to evaluate the synergy of the two? One thing is for sure, new avenues are about to be travelled. No competing interests declared. MR is responsible for the conception and design of the work; the acquisition or analysis or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; and final approval of the version submitted for publication. MR agrees to be accountable for all aspects of the work. No funding was received. I gratefully thank Dr Lasse Gliemann and Mads Fisher for providing helpful insights and feedback during the preparation of the manuscript.