Transcranial Auricular Vagus Nerve Stimulation (taVNS) and Ear-EEG: Potential for Closed-Loop Portable Non-invasive Brain Stimulation

No matter how hard we concentrate, our attention fluctuates – a fact that greatly affects our success in completing a current task. Here, we review work from two methods that, in a closed-loop manner, have the potential to ameliorate these fluctuations. Ear-EEG can measure electric brain activity from areas in or around the ear, using small and thus portable hardware. It has been shown to capture the state of attention with high temporal resolution. Transcutaneous auricular vagus nerve stimulation (taVNS) comes with the same advantages (small and light) and critically current research suggests that it is possible to influence ongoing brain activity that has been linked to attention. Following the review of current work on ear-EEG and taVNS we suggest that a combination of the two methods in a closed-loop system could serve as a potential application to modulate attention

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 STATEMENTtaVNS 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

I spy with my little eye: The detection of changes in emotional faces and the influence of facial feedback in Parkinson disease

Background and purpose Parkinson disease (PD) is a progressive neurodegenerative disorder that affects the motor system but also involves deficits in emotional processing such as facial emotion recognition. In healthy participants, it has been shown that facial mimicry, the automatic imitation of perceived facial expressions, facilitates the interpretation of the emotional states of our counterpart. In PD patients, recent studies revealed reduced facial mimicry and consequently reduced facial feedback, suggesting that this reduction might contribute to the prominent emotion recognition deficits found in PD. Methods We investigated the influence of facial mimicry on facial emotion recognition. Twenty PD patients and 20 healthy controls (HCs) underwent a classical facial mimicry manipulation (holding a pen with the lips, teeth, or nondominant hand) while performing an emotional change detection task with faces. Results As expected, emotion recognition was significantly influenced by facial mimicry manipulation in HCs, further supporting the hypothesis of facial feedback and the related theory of embodied simulation. Importantly, patients with PD, generally and independent from the facial mimicry manipulation, were impaired in their ability to detected emotion changes. Our data further show that PD patients' facial emotional recognition abilities are completely unaffected by mimicry manipulation, suggesting that PD patients cannot profit from an artificial modulation of the already impaired facial feedback. Conclusions These findings suggest that it is not the hypomimia and the absence of facial feedback per se, but a disruption of the facial feedback loop, that leads to the prominent emotion recognition deficit in PD patients

Transcutaneous Vagus Nerve Stimulation (tVNS) and the Dynamics of Visual Bistable Perception

Transcutaneous vagus nerve stimulation (tVNS) is widely used for clinical applications, but its mechanism of action is poorly understood. One candidate pathway that might mediate the effects of tVNS is an increase in GABAergic neurotransmission. In this study, we investigated the effect of tVNS on visual bistable perception, which is highly coupled to GABA. Participants were 34 healthy young subjects. We used a static (Necker cube) and a dynamic (structure from motion) bistable perception task. Each subject underwent tVNS as well as sham (placebo) stimulation for ∼45 min. We analyze effects of tVNS on percept durations by means of Bayesian multilevel regression. We find no evidence for a modulation of bistable perception dynamics through tVNS in either task, but the analyses do not ultimately confirm the null hypothesis either. We discuss different possible implications of our finding and propose that GABAergic effects of tVNS should be further investigated using more direct measures of GABA concentration, and, more generally, that a better understanding of the mechanisms of action of vagus nerve stimulation is needed. Finally, we discuss limitations of our study design, data analysis, and conclusions

Amplitude modulated transcranial alternating current stimulation (AM-TACS) efficacy evaluation via phosphene induction

Amplitude modulated transcranial alternating current stimulation (AM-tACS) is a novel method of electrostimulation which enables the recording of electrophysiological signals during stimulation, thanks to an easier removable stimulation artefact compared to classical electrostimulation methods. To gauge the neuromodulatory potential of AM-tACS, we tested its capacity to induce phosphenes as an indicator of stimulation efficacy. AM-tACS was applied via a two-electrode setup, attached on FpZ and below the right eye. AM-tACS waveforms comprised of different carrier (50 Hz, 200 Hz, 1000 Hz) and modulation frequencies (8 Hz, 16 Hz, 28 Hz) were administered with at maximum 2 mA peakto- peak stimulation strength. TACS conditions in the same frequencies were used as a benchmark for phosphene induction. AM-tACS conditions using a 50 Hz carrier frequency were able to induce phosphenes, but with no difference in phosphene thresholds between modulation frequencies. AM-tACS using a 200 Hz or 1000 Hz carrier frequency did not induce phosphenes. TACS conditions induced phosphenes in line with previous studies. Stimulation effects of AM-tACS conditions were independent of amplitude modulation and instead relied solely on the carrier frequency. A possible explanation may be that AM-tACS needs higher stimulation intensities for its amplitude modulation to have a neuromodulatory effect

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

Perceptibility and Pain Thresholds in Low- and High-Frequency Alternating Current Stimulation: Implications for tACS and tTIS

Background: Transcranial electrical stimulation (tES) has emerged as a promising tool for neuromodulation, but its application is often limited by the discomfort associated with higher stimulation intensities. Newer variants like transcranial temporal interference stimulation (tTIS) utilize high-frequency alternating currents (≥ 500 Hz) to penetrate deeper brain regions while mitigating perceptual discomfort. Objective: This study sought to examine sensation and pain thresholds across various stimulation frequencies of alternating currents, aiming to explore the boundaries of comfortable intensities. Additionally, we sought to evaluate the efficacy of an anesthetizing topical cream in increasing participant comfort and potentially extending the range of tolerable stimulation levels. Method: We recruited 37 participants and applied alternating current stimulation to the head at various frequencies (10 Hz, 20 Hz, 500 Hz, 1000 Hz, and 2000 Hz) to determine intensity dependent perception- and pain thresholds. Additionally, thresholds were determined under the influence of a topical anesthetic. Results: Our findings confirm that as stimulation frequency increases, perceptibility decreases, with higher frequencies allowing a manyfold increase in stimulation intensity before becoming perceptible or causing pain. Additionally, the anesthetizing cream was efficacious in further reducing perceptibility and pain sensations across all frequencies. Conclusion: This study lays the groundwork for future research by establishing comfortable limits for stimulation intensities, particularly in the context of high-frequency stimulation. The reduced perceptibility of high-frequency stimulation, coupled with the effectiveness of anesthetizing creams, enables the administration of higher stimulation intensities for more potent neuromodulatory interventions without causing discomfort

Pulsed transcranial electric brain stimulation enhances speech comprehension

Background: One key mechanism thought to underlie speech processing is the alignment of cortical brain rhythms to the acoustic input, a mechanism termed entrainment. Recent work showed that transcranial electrical stimulation (tES) in speech relevant frequencies or adapted to the speech envelope can in fact enhance speech processing. However, it is unclear whether an oscillatory tES is necessary, or if transients in the stimulation (e.g., peaks in the tES signal) at relevant times are sufficient. Objective: In this study we used a novel pulsed-tES-protocol and tested behaviorally if a transiently pulsed - instead of a persistently oscillating - tES signal, can improve speech processing. Methods: While subjects listened to spoken sentences embedded in noise, brief electric direct current pulses aligned to speech transients (syllable onsets) were applied to auditory cortex regions to modulate comprehension. Additionally, we modulated the temporal delay between tES-pulses and speech transients to test for periodic modulations of behavior, indicative of entrainment by tES. Results: Speech comprehension was improved when tES-pulses were applied with a delay of 100 ms in respect to the speech transients. Contradictory to previous reports we find no periodic modulation of behavior. However, we find indications that periodic modulations can be spurious results of sampling behavioral data too coarsely. Conclusions: Subject’s speech comprehension benefits from pulsed-tES, yet behavior is not modulated periodically. Thus, pulsed-tES can aid cortical entrainment to speech input, which is especially relevant in a noisy environment. Yet, pulsed-tES does not seem to entrain brain oscillations by itself

Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (four female, two male; plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition

Inconsistent effects of stochastic resonance on human auditory processing

It has been demonstrated that, while otherwise detrimental, noise can improve sensory perception under optimal conditions. The mechanism underlying this improvement is stochastic resonance. An inverted U-shaped relationship between noise level and task performance is considered as the signature of stochastic resonance. Previous studies have proposed the existence of stochastic resonance also in the human auditory system. However, the reported beneficial effects of noise are small, based on a small sample, and do not confirm the proposed inverted U-shaped function. Here, we investigated in two separate studies whether stochastic resonance may be present in the human auditory system by applying noise of different levels, either acoustically or electrically via transcranial random noise stimulation, while participants had to detect acoustic stimuli adjusted to their individual hearing threshold. We find no evidence for behaviorally relevant effects of stochastic resonance. Although detection rate for near-threshold acoustic stimuli appears to vary in an inverted U-shaped manner for some subjects, it varies in a U-shaped manner or in other manners for other subjects. Our results show that subjects do not benefit from noise, irrespective of its modality. In conclusion, our results question the existence of stochastic resonance in the human auditory system