Phasic, Event-Related Transcutaneous Auricular Vagus Nerve Stimulation Modifies Behavioral, Pupillary, and Low-Frequency Oscillatory Power Responses.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed to activate the locus ceruleus-noradrenaline (LC-NA) system. However, previous studies failed to find consistent modulatory effects of taVNS on LC-NA biomarkers. Previous studies suggest that phasic taVNS may be capable of modulating LC-NA biomarkers such as pupil dilation and alpha oscillations. However, it is unclear whether these effects extend beyond pure sensory vagal nerve responses. Critically, the potential of the pupillary light reflex as an additional taVNS biomarker has not been explored so far. Here, we applied phasic active and sham taVNS in 29 subjects (16 female, 13 male) while they performed an emotional Stroop task (EST) and a passive pupil light reflex task (PLRT). We recorded pupil size and brain activity dynamics using a combined Magnetoencephalography (MEG) and pupillometry design. Our results show that phasic taVNS significantly increased pupil dilation and performance during the EST. During the PLRT, active taVNS reduced and delayed pupil constriction. In the MEG, taVNS increased frontal-midline theta and alpha power during the EST, whereas occipital alpha power was reduced during both the EST and PLRT. Our findings provide evidence that phasic taVNS systematically modulates behavioral, pupillary, and electrophysiological parameters of LC-NA activity during cognitive processing. Moreover, we demonstrate for the first time that the pupillary light reflex can be used as a simple and effective proxy of taVNS efficacy. These findings have important implications for the development of noninvasive neuromodulation interventions for various cognitive and clinical applications.SIGNIFICANCE STATEMENT taVNS has gained increasing attention as a noninvasive neuromodulation technique and is widely used in clinical and nonclinical research. Nevertheless, the exact mechanism of action of taVNS is not yet fully understood. By assessing physiology and behavior in a response conflict task in healthy humans, we demonstrate the first successful application of a phasic, noninvasive vagus nerve stimulation to improve cognitive control and to systematically modulate pupillary and electrophysiological markers of the noradrenergic system. Understanding the mechanisms of action of taVNS could optimize future clinical applications and lead to better treatments for mental disorders associated with noradrenergic dysfunction. In addition, we present a new taVNS-sensitive pupillary measure representing an easy-to-use biomarker for future taVNS studies.

Effects of transcutaneous auricular vagus nerve stimulation paired with tones on electrophysiological markers of auditory perception.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (taVNS) has been introduced as a non-invasive alternative to invasive vagus nerve stimulation (iVNS). While iVNS paired with tones has been highlighted as a potential effective therapy for the treatment of auditory disorders such as tinnitus, there is still scarce data available confirming the efficacy of non-invasive taVNS. Here, we assessed the effect of taVNS paired with acoustic stimuli on sensory-related electrophysiological responses. METHODS: A total of 22 healthy participants were investigated with a taVNS tone-pairing paradigm using a within-subjects design. In a single session pure tones paired with either active taVNS or sham taVNS were repeatedly presented. Novel tones without electrical stimulation served as control condition. Auditory event related potentials and auditory cortex oscillations were compared before and after the tone pairing procedure between stimulation conditions. RESULTS: From pre to post pairing, we observed a decrease in the N1 amplitude and in theta power to tones paired with sham taVNS while these electrophysiological measures remained stable for tones paired with active taVNS a pattern mirroring auditory sensory processing of novel, unpaired control tones. CONCLUSION: Our results demonstrate the efficacy of a short-term application of non-invasive taVNS to modulate auditory processing in healthy individuals and, thereby, have potential implications for interventions in auditory processing deficits.

Current challenges in reliably targeting the noradrenergic locus coeruleus using transcutaneous auricular vagus nerve stimulation (taVNS).

Transcutaneous auricular vagus nerve stimulation (taVNS), as a non-invasive brain stimulation technique may influence the locus coeruleus-norepinephrine system (LC-NE system) via modulation of the Vagus Nerve (VN) which projects to the LC. Few human studies exist examining the effects of taVNS on the LC-NE system and studies to date assessing the ability of taVNS to target the LC yield heterogeneous results. The aim of this review is to present an overview of the current challenges in assessing effects of taVNS on LC function and how translational approaches spanning animal and human research can help in this regard. A particular emphasis of the review discusses how the effects of taVNS may be influenced by changes in structure and function of the LC-NE system across the human lifespan and in disease.

Mind-wandering Is Accompanied by Both Local Sleep and Enhanced Processes of Spatial Attention Allocation.

Mind-wandering (MW) is a subjective, cognitive phenomenon, in which thoughts move away from the task toward an internal train of thoughts, possibly during phases of neuronal sleep-like activity (local sleep, LS). MW decreases cortical processing of external stimuli and is assumed to decouple attention from the external world. Here, we directly tested how indicators of LS, cortical processing, and attentional selection change in a pop-out visual search task during phases of MW. Participants' brain activity was recorded using magnetoencephalography, MW was assessed via self-report using randomly interspersed probes. As expected, the performance decreased under MW. Consistent with the occurrence of LS, MW was accompanied by a decrease in high-frequency activity (HFA, 80-150 Hz) and an increase in slow wave activity (SWA, 1-6 Hz). In contrast, visual attentional selection as indexed by the N2pc component was enhanced during MW with the N2pc amplitude being directly linked to participants' performance. This observation clearly contradicts accounts of attentional decoupling that would predict a decrease in attention-related responses to external stimuli during MW. Together, our results suggest that MW occurs during phases of LS with processes of attentional target selection being upregulated, potentially to compensate for the mental distraction during MW.

Effects of transcutaneous vagus nerve stimulation (tVNS) on beta and gamma brain oscillations.

Physiological and behavioral effects induced through transcutaneous vagus nerve stimulation (tVNS) are under scrutiny in a growing number of studies, yet its mechanisms of action remain poorly understood. One candidate mechanism is a modulation of γ-aminobutyric acid (GABA) transmission through tVNS. Two recent behavioral studies suggest that such a GABAergic effect might occur in a lateralized fashion, i.e., the GABA modulation might be stronger in the left than in the right brain hemisphere after tVNS applied to the left ear. Using magnetoencephalography (MEG), we tested for GABA-associated modulations in resting and event-related brain oscillations and for a lateralization of those effects in a sample of 41 healthy young adults. Our data provide substantial evidence against all hypotheses, i.e., we neither find effects of tVNS on oscillatory power nor a lateralization of effects.