The effects of non-invasive cranial nerve neuromodulation on the autonomic nervous system in human research participants

The normal ageing process is underpinned by progressive autonomic nervous system dysfunction, which can lead to the development of conditions such as heart failure. In recent years there has been substantial interest in the therapeutic potential of electrical neuromodulatory therapies such as vagus nerve stimulation. However, vagus nerve stimulation is an invasive technique requiring the use of a surgical procedure and non-invasive methods could have greater clinical utility. This thesis investigated the cardiovascular autonomic effects of two non-invasive cranial nerve neuromodulatory techniques in humans: transcutaneous vagus nerve stimulation (tVNS) and non-invasive trigeminal nerve stimulation (TNS). tVNS applied to the tragus of the ear to stimulate the auricular branch of the vagus nerve (ABVN) was found to increase heart rate variability and baroreflex sensitivity in healthy older participants (n = 18) and patients with heart failure (n = 8). Microneurography in aged volunteers (n = 5) showed this change in autonomic function may have been partly due to a reduction in muscle sympathetic nerve activity (MSNA). However a validation study of stimulation at different ear sites detected a similar change in HRV elicited by helix stimulation in a subset of healthy volunteers (n = 12), suggesting a role for the auriculotemporal (trigeminal) nerve, which also innervates the tragus, in the observed autonomic effects. TNS applied to supraorbital region in healthy participants (n = 26) found no evidence however of changes in HRV or BRS, suggesting that this technique has a limited effect on cardiovascular autonomic function. Further clinical studies are needed to determine if tVNS applied to the tragus could be an effective adjunctive therapy for disorders where autonomic dysregulation is present. In addition, the precise mechanisms behind the autonomic effects of tVNS should be further investigated in animal studies in order to optimise the technique and inform future translational studies.