Transcutaneous vagus nerve stimulation does not affect verbal memory performance in healthy volunteers

Introduction: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders. Methods: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition. Results: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores. Conclusion: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits

The potential for autonomic neuromodulation to reduce perioperative complications and pain: a systematic review and meta-analysis

BACKGROUND: Autonomic dysfunction promotes organ injury after major surgery through numerous pathological mechanisms. Vagal withdrawal is a key feature of autonomic dysfunction, and it may increase the severity of pain. We systematically evaluated studies that examined whether vagal neuromodulation can reduce perioperative complications and pain. METHODS: Two independent reviewers searched PubMed, EMBASE, and the Cochrane Register of Controlled Clinical Trials for studies of vagal neuromodulation in humans. Risk of bias was assessed; I2 index quantified heterogeneity. Primary outcomes were organ dysfunction (assessed by measures of cognition, cardiovascular function, and inflammation) and pain. Secondary outcomes were autonomic measures. Standardised mean difference (SMD) using the inverse variance random-effects model with 95% confidence interval (CI) summarised effect sizes for continuous outcomes. RESULTS: From 1258 records, 166 full-text articles were retrieved, of which 31 studies involving patients (n=721) or volunteers (n=679) met the inclusion criteria. Six studies involved interventional cardiology or surgical patients. Indirect stimulation modalities (auricular [n=23] or cervical transcutaneous [n=5]) were most common. Vagal neuromodulation reduced pain (n=10 studies; SMD=2.29 [95% CI, 1.08-3.50]; P=0.0002; I2=97%) and inflammation (n=6 studies; SMD=1.31 [0.45-2.18]; P=0.003; I2=91%), and improved cognition (n=11 studies; SMD=1.74 [0.96-2.52]; P<0.0001; I2=94%) and cardiovascular function (n=6 studies; SMD=3.28 [1.96-4.59]; P<0.00001; I2=96%). Five of six studies demonstrated autonomic changes after vagal neuromodulation by measuring heart rate variability, muscle sympathetic nerve activity, or both. CONCLUSIONS: Indirect vagal neuromodulation improves physiological measures associated with limiting organ dysfunction, although studies are of low quality, are susceptible to bias and lack specific focus on perioperative patients

The Neuromodulatory and Hormonal Effects of Transcutaneous Vagus Nerve Stimulation as Evidenced by Salivary Alpha Amylase, Salivary Cortisol, Pupil Diameter, and the P3 Event-Related Potential

Background Transcutaneous vagus nerve stimulation (tVNS) is a new, non-invasive technique being investigated as an intervention for a variety of clinical disorders, including epilepsy and depression. It is thought to exert its therapeutic effect by increasing central norepinephrine (NE) activity, but the evidence supporting this notion is limited. Objective In order to test for an impact of tVNS on psychophysiological and hormonal indices of noradrenergic function, we applied tVNS in concert with assessment of salivary alpha amylase (SAA) and cortisol, pupil size, and electroencephalograph (EEG) recordings. Methods Across three experiments, we applied real and sham tVNS to 61 healthy participants while they performed a set of simple stimulus-discrimination tasks. Before and after the task, as well as during one break, participants provided saliva samples and had their pupil size recorded. EEG was recorded throughout the task. The target for tVNS was the cymba conchae, which is heavily innervated by the auricular branch of the vagus nerve. Sham stimulation was applied to the ear lobe. Results P3 amplitude was not affected by tVNS (Experiment 1A: N = 24; Experiment 1B: N = 20; Bayes factor supporting null model = 4.53), nor was pupil size (Experiment 2: N = 16; interaction of treatment and time: p = .79). However, tVNS increased SAA (Experiments 1A and 2: N = 25) and attenuated the decline of salivary cortisol compared to sham (Experiment 2: N = 17), as indicated by significant interactions involving treatment and time (p = .023 and p = .040, respectively). Conclusion These findings suggest that tVNS modulates hormonal indices but not psychophysiological indices of noradrenergic function

Transcutaneous vagus nerve stimulation and extinction of prepared fear: A conceptual non-replication

Stress-related psychiatric disorders across the life spa

Transcutaneous vagus nerve stimulation via tragus or cymba conchae: Are its psychophysiological effects dependent on the stimulation area?

Efforts in optimizing transcutaneous vagus nerve stimulation (tVNS) are crucial to further develop its potential in improving cognitive and autonomic regulation. The present study focused on this topic. The aim was to compare for the first time the main stimulation areas of the ear currently used in studies with tVNS, taking cognitive as well as neurophysiological effects into account. The main areas to be compared with one another were tragus, cymba conchae, and earlobe (sham) stimulation. Post-error slowing, which has already been shown to be influenced by tVNS, was used to investigate the cognitive effects of tVNS when applied on the different auricular areas. On the neurophysiological level, we measured pupillary responses as an index of norepinephrine activity during post-error slowing, and cardiac vagal activity to investigate the activation of neural pathways involved in post-error slowing. Stimulation of different auricular areas led to no differences in post-error slowing and in pupillary responses. However, the neurological processes involved in post-error slowing could be observed, since norepinephrine activity increased after committing an error. Further, there was an increase in cardiac vagal activity over the test period that was independent of the stimulation areas. The results suggest that tVNS targeting the ear might have a non-specific effect on the processing of error commission, on pupillary responses, and on cardiac vagal activity. We conclude that it is necessary to consider alternatives for sham conditions other than electrical earlobe stimulation. [Abstract copyright: Copyright © 2021 Elsevier B.V. All rights reserved.

The effect of transcutaneous auricular Vagal Nerve Stimulation (taVNS) on P3 event-related potentials during a Bayesian oddball task

FSW - Action Control - Ou

Transcutaneous Vagus Nerve Stimulation Enhances Post-error Slowing

FSW - Self-regulation models for health behavior and psychopathology - ou