Transcutaneous auricular vagus nerve stimulation modulates the processing of interoceptive prediction error signals and their role in allostatic regulation.

It has recently been suggested that predictive processing principles may apply to interoception, defined as the processing of hormonal, autonomic, visceral, and immunological signals. In the current study, we aimed at providing empirical evidence for the role of cardiac interoceptive prediction errors signals on allostatic adjustments, using transcutaneous auricular vagus nerve stimulation (taVNS) as a tool to modulate the processing of interoceptive afferents. In a within-subject design, participants performed a cardiac-related interoceptive task (heartbeat counting task) under taVNS and sham stimulation, spaced 1-week apart. We observed that taVNS, in contrast to sham stimulation, facilitated the maintenance of interoceptive accuracy levels over time (from the initial, stimulation-free, baseline block to subsequent stimulation blocks), suggesting that vagus nerve stimulation may have helped to maintain engagement to cardiac afferent signals. During the interoceptive task, taVNS compared to sham, produced higher heart-evoked potentials (HEP) amplitudes, a potential readout measure of cardiac-related prediction error processing. Further analyses revealed that the positive relation between interoceptive accuracy and allostatic adjustments-as measured by heart rate variability (HRV)-was mediated by HEP amplitudes. Providing initial support for predictive processing accounts of interoception, our results suggest that the stimulation of the vagus nerve may increase the precision with which interoceptive signals are processed, favoring their influence on allostatic adjustments.

Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: A pooled mega-analysis.

BACKGROUND: Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet. METHODS: The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release. RESULTS: While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity. CONCLUSION(S): Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research.

Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control.

Response conflicts play a prominent role in the flexible adaptation of behavior as they represent context-signals that indicate the necessity for the recruitment of cognitive control. Previous studies have highlighted the functional roles of the affectively aversive and arousing quality of the conflict signal in triggering the adaptation process. To further test this potential link with arousal, participants performed a response conflict task in two separate sessions with either transcutaneous vagus nerve stimulation (tVNS), which is assumed to activate the locus coeruleus-noradrenaline (LC-NE) system, or with neutral sham stimulation. In both sessions the N2 and P3 event-related potentials (ERP) were assessed. In line with previous findings, conflict interference, the N2 and P3 amplitude were reduced after conflict. Most importantly, this adaptation to conflict was enhanced under tVNS compared to sham stimulation for conflict interference and the N2 amplitude. No effect of tVNS on the P3 component was found. These findings suggest that tVNS increases behavioral and electrophysiological markers of adaptation to conflict. Results are discussed in the context of the potentially underlying LC-NE and other neuromodulatory (e.g., GABA) systems. The present findings add important pieces to the understanding of the neurophysiological mechanisms of conflict-triggered adjustment of cognitive control.