Tonic and phasic transcutaneous auricular vagus nerve stimulation (taVNS) both evoke rapid and transient pupil dilation

Brain stimulation, Journal Year: 2024, Volume and Issue: 17(2), P. 233 - 244

Published: Feb. 28, 2024

BackgroundTranscutaneous auricular vagus nerve stimulation (tVNS or taVNS) is a non-invasive method of electrical the afferent pathway nerve, suggested to drive changes in putative physiological markers noradrenergic activity, including pupil dilation.ObjectiveHowever, it unknown whether different taVNS modes can map onto phasic and tonic activity. The effects on dilation humans are inconsistent, largely due differences protocols. Here, we attempted address these issues.MethodsWe investigated under (1 s) (30 taVNS, pre-registered, single-blind, sham-controlled, within-subject cross-over design, absence behavioural task.ResultsPhasic induced rapid increase size over baseline, significantly greater than sham stimulation, which rapidly declined after offset. Tonic similarly (and larger sham) returning baseline within 5 s, despite ongoing stimulation. Thus, both active closely resembled effect. There were no size, sustained size.ConclusionsThese results suggest that phasic- tonic-like standard parameters may modulate primarily mode as indexed by evoked dilation, above somatosensory effects. This result sheds light temporal profile with implications for their applicability further research.

Language: Английский

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Does transcutaneous auricular vagus nerve stimulation alter pupil dilation? A living Bayesian meta-analysis

Brain stimulation, Journal Year: 2025, Volume and Issue: 18(2), P. 148 - 157

Published: Jan. 29, 2025

Language: Английский

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Three Hundred Hertz Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) Impacts Pupil Size Non‐Linearly as a Function of Intensity

Psychophysiology, Journal Year: 2025, Volume and Issue: 62(2)

Published: Feb. 1, 2025

ABSTRACT Transcutaneous auricular vagus nerve stimulation (taVNS) is a neuromodulatory technique that may have numerous potential health and human performance benefits. However, optimal parameters for maximizing taVNS efficacy are unknown. Progress impeded by disagreement on the identification of biomarker reliably indexes activation systems targeted taVNS, including locus coeruleus‐norepinephrine (LC‐NE) system. Pupil size varies with LC‐NE activity one has shown inconsistent sensitivity to in prior studies. The present study examined relationship between pupil using promising behavioral effects studies but received comparatively little attention. Participants trains 50 μs pulses delivered continuously below perceptual threshold at 300 Hz left external acoustic meatus (EAM) while was recorded during pupillary light reflex task. Analysis generalized additive mixed modeling (GAMM) revealed non‐linear intensity diameter. Active increased participants who 2 approximately 4.8 mA, not higher‐intensity (up 8.1 mA). In addition, persisted subsequent blocks, mitigating decreases over course These findings suggest activates system when applied EAM, its be counteracted higher intensities.

Language: Английский

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No evidence for a modulating effect of continuous transcutaneous auricular vagus nerve stimulation on markers of noradrenergic activity

Psychophysiology, Journal Year: 2022, Volume and Issue: 59(4)

Published: Jan. 6, 2022

Abstract Although transcutaneous auricular vagus nerve stimulation (taVNS) is thought to increase central noradrenergic activity, findings supporting such mechanism are scarce and inconsistent. This study aimed investigate whether taVNS modulates indirect markers of phasic tonic activity. Sixty‐six healthy participants performed a novelty auditory oddball task twice on separate days: once while receiving (left cymba concha), during sham earlobe) stimulation. To maximize potential effects, the was delivered continuously (frequency: 25 Hz; width: 250 μs) at an intensity individually calibrated maximal level below pain threshold. The administered 10 min before maintained throughout session. Event‐related pupil dilation (ERPD) target stimuli pre‐stimulus baseline size were assessed as respectively. Prior end stimulation, rest, cortisol, salivary alpha‐amylase Finally, we explored effect cardiac vagal respiratory rate, flow rate. Results showed greater ERPD both compared standard in task. In contrast our hypotheses, did not impact any tested markers. Our strongly suggest that continuous concha with parameters ineffective activity via pathway.

Language: Английский

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Transcutaneous Auricular Vagus Stimulation Improves Gait and Reaction Time in Parkinson's Disease

Movement Disorders, Journal Year: 2022, Volume and Issue: 37(10), P. 2163 - 2164

Published: July 21, 2022

Recent studies have found that transcutaneous cervical vagus nerve stimulation (VNS) can improve gait symptoms in Parkinson's disease (PD).1-3 Noninvasive VNS be performed also on the auricular branch of nerve, with significant opportunities terms feasibility and costs. Data effects (taVNS) PD, however, are still missing. Hence we aimed at investigating taVNS 12 patients idiopathic which were consecutively enrolled a pilot-controlled study double-blind randomized crossover design, tertiary movement disorders clinic our institution. Patients selected according to following criteria: (1) chronic levodopa therapy without history levodopa-induced dyskinesias, (2) walking difficulties but able walk unassisted (Unified Disease Rating Scale [UPDRS] Part II item 15 = 1 or 2), (3) modified Hoehn & Yahr score <3 while medication. early signs cognitive impairment atypical parkinsonism individuals anticholinergics and/or affected by any other known condition influence not included. Therapy changes between visits allowed. was delivered either left internal tragus (real) earlobe (control) trains lasting 30 seconds each, composed 600 pulses (frequency 20 Hz; duration 0.3 millisecond) repeated every 4.5 minutes for (six cycles) (Supporting Information Materials). one after week, all subjects crossed over other. evaluated before UPDRS III, flanker test (reaction time), digital 10-m timed up go (10mTUG) duplicate (Mon4t clinic, https://mon4t.com), Visual Analogue (VAS 0–10, "How do you perceive your performance?"). The is an acknowledged VNS-responsive parameter,4 10mTUG provides data total time (stand, rotation, sit, speed, stride length, number steps, mediolateral sway, swing amplitude.5 experiments took place morning levodopa. patients' awareness about (i.e., whether real control) verified questionnaire Variables presented as mean ± standard deviation. tested normality (Shapiro–Wilks test), compared through t Wilcoxon signed rank paired (JMP software v16.0; SAS Institute Inc.), corrected multiple comparisons Benjamini–Hochberg method (false discovery rate set 0.05).3 Demographic features reported Table S1. All completed both control stimulation; no dropouts reported. Baseline similar two (Table S2). III scores showed improvement stimulation, likely because placebo effect; scales better trend stimulation. Stride amplitude, only taVNS. Rotation time, stand sit did show variation. Finally, reaction improved taVNS, corroborating findings. Differences across variables conditions 1. This first experiment reporting systematic evaluation PD. In this sample mild-to-moderate add-on several objective parameters. Despite direct being collected, putative effect persisted motor assessment, (mean completion 52 13.7 seconds), consecutive assessments (single 28 7.3 seconds). latter might give useful information future biomarker (eg, neurophysiological) studies.6 Preclinical structural functional aspects PD.7 Even though its mechanism action debated, entrain ascending cholinergic noradrenergic pathways,6, 8 involved processing locomotor abilities.4, 7 study, some dopamine-dependent parameters length).9 If proven true, would add growing literature association dopaminergic system.10 However, despite results line recent noninvasive experiments,1-3 it possible draw firm conclusion. Indeed, collected PD single sensor. trusted methodology, use more comprehensive analysis system allow precise gait-related issues (ie, freezing).1, 3 Moreover, should replicated larger sample, allowing robust statistical eventually exploring dosage duration.11 Nonetheless, given manageability portable commercialized devices, they may considered valuable tool neuromodulation landscape We acknowledge their kindness availability. Open Access Funding provided Universita Campus Bio-Medico di Roma within CRUI-CARE Agreement. Research project: A. Conception, B. Organization, C. Execution; Statistical Analysis: Design, Execution, Review Critique; Manuscript: Writing draft, Critique. M.M.: 1A, 1B, 1C, 2A, 2B, 3A, 3B. G.A.: 1C. G.M.: A.M.: V.P.: F.C.: 2C, V.D.L.: 3C. M.M. received speakers' honoraria from AbbVie Sanofi. G.A., G.M., A.M., V.P., F.C., V.D.L. deny financial disclosure preceding months. support findings available corresponding author upon reasonable request. Appendix S1 Supporting Please note: publisher responsible content functionality supporting supplied authors. Any queries (other than missing content) directed article.

Language: Английский

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

Journal of Neuroscience, Journal Year: 2023, Volume and Issue: 43(36), P. 6306 - 6319

Published: Aug. 17, 2023

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

Language: Английский

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Multi-session transcutaneous auricular vagus nerve stimulation for Parkinson's disease: evaluating feasibility, safety, and preliminary efficacy

Frontiers in Neurology, Journal Year: 2023, Volume and Issue: 14

Published: July 18, 2023

In pre-clinical animal models of Parkinson's disease (PD), vagus nerve stimulation (VNS) can rescue motor deficits and protect susceptible neuronal populations. Transcutaneous auricular (taVNS) has emerged as a non-invasive alternative to traditional invasive cervical VNS. This is the first report summarizing safety, feasibility, preliminary efficacy repeated sessions taVNS in participants with PD.

Language: Английский

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New tools for shaping plasticity to enhance recovery after stroke

Handbook of clinical neurology, Journal Year: 2022, Volume and Issue: unknown, P. 299 - 315

Published: Jan. 1, 2022

Language: Английский

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tVNS in Stroke: A Narrative Review on the Current State and the Future

Stroke, Journal Year: 2023, Volume and Issue: 54(10), P. 2676 - 2687

Published: Aug. 30, 2023

Ischemic stroke is a leading cause of disability and there paucity therapeutic strategies that promote functional recovery after stroke. Transcutaneous vagus nerve stimulation (tVNS) has shown promising evidence as tool to reduce infarct size in animal models hyperacute In chronic stroke, tVNS paired with limb movements been enhance neurological recovery. this review, we summarize the current for preclinical clinical trials humans. We highlight mechanistic pathways involved beneficial effects tVNS. critically evaluate gaps knowledge recommend key areas research required translate into practice acute

Language: Английский

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Effects of Transcutaneous Auricular Vagus Nerve Stimulation on the P300: Do Stimulation Duration and Stimulation Type Matter?

Brain Sciences, Journal Year: 2024, Volume and Issue: 14(7), P. 690 - 690

Published: July 10, 2024

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has attracted increasing interest as a neurostimulation tool with potential applications in modulating cognitive processes such attention and memory, possibly through the modulation of locus–coeruleus noradrenaline system. Studies examining P300 brain-related component correlate noradrenergic activity, however, have yielded inconsistent findings, due to differences parameters, thus necessitating further investigation. In this event-related study involving 61 participants, therefore, we examined how changes taVNS specifically type (interval vs. continuous stimulation) duration, influence amplitudes during visual novelty oddball task. Although no effects were found over whole cluster time window P300, cluster-based permutation tests revealed distinct impact on response for small electrode cluster, characterized by larger observed easy targets (i.e., stimuli that are easily discernible from standards) following compared sham stimulation. Notably, our findings suggested significantly modulated showing (taVNS sham) hard standards interval We interaction duration target-related P300. While align previous research, investigation is warranted fully elucidate its utility reliable marker neuromodulation field.

Language: Английский

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