Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Keute, Marius; Machetanz, Kathrin; Berelidze, Levan; Guggenberger, Robert; Gharabaghi, Alireza

doi:10.1016/j.brs.2021.01.001

Cited by 44 publications

(38 citation statements)

References 44 publications

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“…Recent work has shown that effects of auricular stimulation on cardiac function do not outlast the stimulation epoch [61]. The short-duration (<1 s), discrete pulse trains used in the present study are less likely to elicit carryover effects observed with continuous, 2-min bouts of stimulation used in previous studies examining inflammatory and neuropeptide responses [62,63].…”

Section: Eye Tracking Configurationmentioning

confidence: 53%

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans

et al. 2021

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Background: Transcutaneous stimulation of the external ear is thought to recruit afferents of the auricular vagus nerve, providing a means to activate noradrenergic pathways in the central nervous system. Findings from human studies examining the effects of auricular stimulation on noradrenergic biomarkers have been mixed, possibly relating to the limited and variable parameter space explored to date. Objective: We tested the extent to which brief pulse trains applied to locations of auricular innervation (canal and concha) elicit acute pupillary responses (PRs) compared to a sham location (lobe). Pulse amplitude and frequency were varied systematically to examine effects on PR features. Methods: Participants (n ¼ 19) underwent testing in three separate experiments, each with stimulation applied to a different external ear location. Perceptual threshold (PT) was measured at the beginning of each experiment. Pulse trains (~600 ms) consisting of different amplitude (0.0xPT, 0.8xPT, 1.0xPT, 1.5xPT, 2.0xPT) and frequency (25 Hz, 300 Hz) combinations were administered during eye tracking procedures. Results: Stimulation to all locations elicited PRs which began approximately halfway through the pulse train and peaked shortly after the final pulse ( 1 s). PR size and incidence increased with pulse amplitude and tended to be greatest with canal stimulation. Higher pulse frequency shortened the latency of PR onset and peak dilation. Changes in pupil diameter elicited by pulse trains were weakly associated with baseline pupil diameter. Conclusion: (s): Auricular stimulation elicits acute PRs, providing a basis to synchronize neuromodulator release with task-related neural spiking which preclinical studies show is a critical determinant of therapeutic effects. Further work is needed to dissociate contributions from vagal and non-vagal afferents mediating activation of the biomarker.

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Section: Eye Tracking Configurationmentioning

confidence: 53%

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans

et al. 2021

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“…A promising approach might be to relate other physiological parameters that have been connected to vagal stimulation to neurostimulation efficacy. As such, the taVNS efficacy in modulating the heart rate ( Badran et al, 2018b ) and coupling of cardiac to neural activity seem promising ( Keute et al, 2021 ) but warrant further investigation as well.…”

Section: A Need For Parametrization Of Tavns Settingsmentioning

confidence: 99%

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

Ruhnau

Zaehle

2021

Front. Hum. Neurosci.

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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.

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“…In line with this suggestion, animal research has shown that stimulating the LC (Liu et al, 2017) and the vagus nerve (Mridha et al, 2021) increases PD in a graded, intensity-dependent way, providing convincing evidence that vagus nerve stimulation modulates phasic LC firing and PD. Notably, one recent study using short pulses (3.4 s) of taVNS in human participants found transient increases in PD following stimulation further suggesting the effectiveness of brief stimulation procedures (Sharon et al, 2021; see also: Keute et al, 2021;Sclocco et al, 2019). With the present pre-registered study (https://aspredicted.org/blind.php?x=56kp3z), our goal was to provide a proof-of-6 concept for the effectiveness of brief, event-related, taVNS in modulating cognitive processes.…”

Section: Introductionmentioning

confidence: 99%

Event-related transcutaneous vagus nerve stimulation modulates behaviour and pupillary responses during an auditory oddball task

Azevedo¹,

Finotti²,

Lernia³

et al. 2021

Preprint

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Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that is thought to activate the Locus Coeruleus-Noradrenaline (LC-NA) system. Standard taVNS protocols consist of the administration of intermittent or continuous stimulation over long periods. However, there is currently limited understanding of temporal dynamics of taVNS modulation of cognitive processes, as well as its mechanisms of action. We argue that novel stimulation approaches, informed by established theories of the LC-NA system, are needed to further our understanding of the neurocognitive underpinnings of taVNS. In this pre-registered study, we tested whether an “event-related” taVNS protocol can modulate the LC-NA system. In a within-subject design (single session) we delivered brief trains of taVNS (3 seconds) during an auditory oddball paradigm. The taVNS was time-locked to the target stimuli and randomly interleaved with sham stimulation. Response times (RT) and stimuli-driven pupillary diameter (PD) were used as indices of LC-NA activity. Results revealed that active taVNS increased RT to targets, as compared to sham trials. Notably, in line with current theories of LC-NA functioning, taVNS modulation of target-related pupil dilation depended on pre-stimulation PD, an index of tonic LC-NA activity. In particular, active (vs. sham) taVNS was associated with smaller pupil dilation in trials where the baseline PD was small. These results demonstrate, for the first time, the effectiveness of brief event-related taVNS in the modulation of cognitive processes and highlight the importance of using pupil size as an index of tonic and phasic LC-NA activity.

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Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects

Cited by 44 publications

References 44 publications

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans

Electrical stimulation of the external ear acutely activates noradrenergic mechanisms in humans

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

Event-related transcutaneous vagus nerve stimulation modulates behaviour and pupillary responses during an auditory oddball task

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