TaVNS Application Timing During Robotic Sensorimotor Task

NCT06294509 | Enrolling By Invitation

• 2 other identifiers: SMTaVNS 20242024-00039
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate the feasibility and effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) in enhancing sensorimotor learning and adaptation. This study will focus on healthy individuals performing a robotic sensorimotor task. Main Questions it Aims to Answer: How does taVNS, with different timing protocols, affect the feasibility and effectiveness of performing a robotic sensorimotor task? What is the impact of taVNS on sensorimotor learning and adaptation? Participants Will: Be pseudo-randomly assigned to one of five experimental groups with different taVNS stimulation timings. Perform a sensorimotor task multiple times across sessions, spanning a maximum of two weeks or until achieving 70% accuracy in two successive sessions. Have kinematic data collected by a robot during the task. Have physiological data measured using external sensors. Fill out questionnaires about the feasibility of taVNS and other subjective measures after each session. Comparison Group: Researchers will compare the four experimental groups to each other to see if different taVNS stimulation timings affect sensorimotor learning outcomes, as well as to a control group that will receive no stimulation.

Conditions

Healthy

Keywords

sensorimotor adaptation; motor learning; transcutaneous auricular Vagus nerve stimulation

Outcome Measures

Primary Outcomes (6)

• Subjectively perceived tolerance of taVNS and perceived difficulty of motor task

  The subjective perceived feasibility of the taVNS stimulation paradigm, perceived difficulty level of the task, assessed by an unvalidated questionnaire on the Likert scale.

  From enrollment to end of study at 2 weeks

• Success of the sensorimotor challenge

  Measured as % of trials where the end-point reaching target (2.4 cm diameter) was reached within an allocated time period (0.5 s +/- 0.067 s).

  After the intervention

• Mean Change from Baseline in Galvanic Skin Response (GSR)

  Physiological dose response to the taVNS using GSR as indicator

  During and immediately after taVNS

• Mean Change from Baseline in Heart Rate (HR)

  Physiological dose response to the taVNS using HR as indicator

  During and immediately after taVNS

• Mean Change from Baseline in Pupil Diameter (PD)

  Physiological dose response to the taVNS using PD as indicator

  During and immediately after taVNS

• Mean Change from Baseline in electroencephalogram (EEG)

  Physiological dose response to the taVNS using EEG as indicator

  During and immediately after taVNS

Secondary Outcomes (3)

• Subjectively perceived positive effects of taVNS on motor performance

  After each session, from enrollment to end of treatment at 2 weeks

• Change of movement parameters from baseline

  After each session, from enrollment to end of study at 2 weeks

• Associations between outcomes

  upon completion of study, at 2 weeks

Study Arms (5)

No stimulation (control)

NO INTERVENTION

Participants will wear device but will not receive any stimulation

Movement-unrelated stimulation (control)

ACTIVE COMPARATOR

Participants will wear device and receive randomly timed stimulation

Device: in-house developed transcutaneous auricular Vagus Nerve Stimulation device

pre-movement taVNS

EXPERIMENTAL

Stimulation will start after 500ms of being in the home position, before the onset of the movement cue.

Device: in-house developed transcutaneous auricular Vagus Nerve Stimulation device

during-movement taVNS

EXPERIMENTAL

Stimulation will occur during the movement phase.

Device: in-house developed transcutaneous auricular Vagus Nerve Stimulation device

post-movement taVNS

EXPERIMENTAL

Stimulation will occur immediately after a successful trial (no stimulation if the trial is failed).

Device: in-house developed transcutaneous auricular Vagus Nerve Stimulation device

Interventions

in-house developed transcutaneous auricular Vagus Nerve Stimulation device DEVICE

taVNS in this study involves short electric pulses (0.25 ms) delivered to the ear's skin to activate the auricular branch of the Vagus. The pulses are current-controlled to ensure stability and delivered in a bipolar fashion to prevent skin irritation. Before each session, taVNS is calibrated for each participant. Starting at 0.1 mA, the intensity is increased stepwise until a comfortable maximum (typically 1.5-2.5 mA) is reached. Stimuli are delivered in short trains lasting 0.5 seconds each, with 13 pulses (0.25ms each) per train. Participants receive a maximum of 150 stimuli per session, totaling a maximum of 75 seconds of cumulative stimulation. Participants adapt their movements over up to six sessions across two weeks. The robotic task facilitates accurate movement tracking and provides interactive real-time feedback.

Movement-unrelated stimulation (control); during-movement taVNS; post-movement taVNS; pre-movement taVNS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy participants above 18 years of age and able to provide informed consent and understand the study requirements

You may not qualify if:

• Individuals with major untreated depression, major cognitive and/or communication deficits, and major comprehension and/or memory deficits that may interfere with the informed consent process, task-specific practice, or communication of adverse events will be excluded from the study.
• Neurological conditions such as epilepsy, participation in any other research trial, pregnancy, use of implanted electrical devices, and use of medication or procedure that interferes with vagal functions.
• Pregnancy or trying to get pregnant.

Sponsors & Collaborators

• Olivier Lambercy: lead

Study Sites (1)

ETH Zurich

Zurich, Canton of Zurich, 8008, Switzerland

Location

Related Publications (24)

• Kim AY, Marduy A, de Melo PS, Gianlorenco AC, Kim CK, Choi H, Song JJ, Fregni F. Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.

  PMID: 36543841 BACKGROUND

• Baig SS, Kamarova M, Bell SM, Ali AN, Su L, Dimairo M, Dawson J, Redgrave JN, Majid A. tVNS in Stroke: A Narrative Review on the Current State and the Future. Stroke. 2023 Oct;54(10):2676-2687. doi: 10.1161/STROKEAHA.123.043414. Epub 2023 Aug 30.

  PMID: 37646161 BACKGROUND

• Badran BW, Peng X, Baker-Vogel B, Hutchison S, Finetto P, Rishe K, Fortune A, Kitchens E, O'Leary GH, Short A, Finetto C, Woodbury ML, Kautz S. Motor Activated Auricular Vagus Nerve Stimulation as a Potential Neuromodulation Approach for Post-Stroke Motor Rehabilitation: A Pilot Study. Neurorehabil Neural Repair. 2023 Jun;37(6):374-383. doi: 10.1177/15459683231173357. Epub 2023 May 20.

  PMID: 37209010 BACKGROUND

• Branscheidt M, Hadjiosif AM, Anaya MA, Keller J, Widmer M, Runnalls KD, Luft AR, Bastian AJ, Krakauer JW, Celnik PA. Reinforcement Learning Is Impaired in the Sub-acute Post-stroke Period. bioRxiv [Preprint]. 2023 Jan 25:2023.01.25.525408. doi: 10.1101/2023.01.25.525408.

  PMID: 36747674 BACKGROUND

• Dietrich S, Smith J, Scherzinger C, Hofmann-Preiss K, Freitag T, Eisenkolb A, Ringler R. A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI. Biomed Tech (Berl). 2008 Jun;53(3):104-11. doi: 10.1515/BMT.2008.022.

  PMID: 18601618 BACKGROUND

• Breton-Provencher V, Drummond GT, Sur M. Locus Coeruleus Norepinephrine in Learned Behavior: Anatomical Modularity and Spatiotemporal Integration in Targets. Front Neural Circuits. 2021 Jun 7;15:638007. doi: 10.3389/fncir.2021.638007. eCollection 2021.

  PMID: 34163331 BACKGROUND

• Gielow MR, Zaborszky L. The Input-Output Relationship of the Cholinergic Basal Forebrain. Cell Rep. 2017 Feb 14;18(7):1817-1830. doi: 10.1016/j.celrep.2017.01.060.

  PMID: 28199851 BACKGROUND

• Izawa J, Shadmehr R. Learning from sensory and reward prediction errors during motor adaptation. PLoS Comput Biol. 2011 Mar;7(3):e1002012. doi: 10.1371/journal.pcbi.1002012. Epub 2011 Mar 10.

  PMID: 21423711 BACKGROUND

• Morrison RA, Hulsey DR, Adcock KS, Rennaker RL 2nd, Kilgard MP, Hays SA. Vagus nerve stimulation intensity influences motor cortex plasticity. Brain Stimul. 2019 Mar-Apr;12(2):256-262. doi: 10.1016/j.brs.2018.10.017. Epub 2018 Nov 3.

  PMID: 30409712 BACKGROUND

• Rodenkirch C, Carmel JB, Wang Q. Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems. Front Neurosci. 2022 Jul 5;16:922424. doi: 10.3389/fnins.2022.922424. eCollection 2022.

  PMID: 35864985 BACKGROUND

• Bowles S, Hickman J, Peng X, Williamson WR, Huang R, Washington K, Donegan D, Welle CG. Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement. Neuron. 2022 Sep 7;110(17):2867-2885.e7. doi: 10.1016/j.neuron.2022.06.017. Epub 2022 Jul 19.

  PMID: 35858623 BACKGROUND

• Donegan D, Kanzler CM, Buscher J, Viskaitis P, Bracey EF, Lambercy O, Burdakov D. Hypothalamic Control of Forelimb Motor Adaptation. J Neurosci. 2022 Aug 10;42(32):6243-6257. doi: 10.1523/JNEUROSCI.0705-22.2022. Epub 2022 Jul 5.

  PMID: 35790405 BACKGROUND

• Wickens JR, Reynolds JN, Hyland BI. Neural mechanisms of reward-related motor learning. Curr Opin Neurobiol. 2003 Dec;13(6):685-90. doi: 10.1016/j.conb.2003.10.013.

  PMID: 14662369 BACKGROUND

• Donegan D, Peleg-Raibstein D, Lambercy O, Burdakov D. Anticipatory countering of motor challenges by premovement activation of orexin neurons. PNAS Nexus. 2022 Oct 25;1(5):pgac240. doi: 10.1093/pnasnexus/pgac240. eCollection 2022 Nov.

  PMID: 36712356 BACKGROUND

• Kanzler CM, Averta G, Schwarz A, Held JPO, Gassert R, Bicchi A, Santello M, Lambercy O, Bianchi M. A low-dimensional representation of arm movements and hand grip forces in post-stroke individuals. Sci Rep. 2022 May 9;12(1):7601. doi: 10.1038/s41598-022-11806-4.

  PMID: 35534629 BACKGROUND

• Lerman I, Davis B, Huang M, Huang C, Sorkin L, Proudfoot J, Zhong E, Kimball D, Rao R, Simon B, Spadoni A, Strigo I, Baker DG, Simmons AN. Noninvasive vagus nerve stimulation alters neural response and physiological autonomic tone to noxious thermal challenge. PLoS One. 2019 Feb 13;14(2):e0201212. doi: 10.1371/journal.pone.0201212. eCollection 2019.

  PMID: 30759089 BACKGROUND

• Mridha Z, de Gee JW, Shi Y, Alkashgari R, Williams J, Suminski A, Ward MP, Zhang W, McGinley MJ. Graded recruitment of pupil-linked neuromodulation by parametric stimulation of the vagus nerve. Nat Commun. 2021 Mar 9;12(1):1539. doi: 10.1038/s41467-021-21730-2.

  PMID: 33750784 BACKGROUND

• Machetanz K, Berelidze L, Guggenberger R, Gharabaghi A. Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets. Auton Neurosci. 2021 Dec;236:102894. doi: 10.1016/j.autneu.2021.102894. Epub 2021 Oct 12.

  PMID: 34662844 BACKGROUND

• Lloyd B, Wurm F, de Kleijn R, Nieuwenhuis S. Short-term transcutaneous vagus nerve stimulation increases pupil size but does not affect EEG alpha power: A replication of Sharon et al. (2021, Journal of Neuroscience). Brain Stimul. 2023 Jul-Aug;16(4):1001-1008. doi: 10.1016/j.brs.2023.06.010. Epub 2023 Jun 20.

  PMID: 37348704 BACKGROUND

• Rong P, Liu J, Wang L, Liu R, Fang J, Zhao J, Zhao Y, Wang H, Vangel M, Sun S, Ben H, Park J, Li S, Meng H, Zhu B, Kong J. Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. J Affect Disord. 2016 May;195:172-9. doi: 10.1016/j.jad.2016.02.031. Epub 2016 Feb 10.

  PMID: 26896810 BACKGROUND

• Badran BW, Yu AB, Adair D, Mappin G, DeVries WH, Jenkins DD, George MS, Bikson M. Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. J Vis Exp. 2019 Jan 7;(143):10.3791/58984. doi: 10.3791/58984.

  PMID: 30663712 BACKGROUND

• Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Istuk N, Lechner S, Klonowski W, Varoneckas G, Szeles JC, Sarolic A. Current Directions in the Auricular Vagus Nerve Stimulation II - An Engineering Perspective. Front Neurosci. 2019 Jul 24;13:772. doi: 10.3389/fnins.2019.00772. eCollection 2019.

  PMID: 31396044 BACKGROUND

• Dabiri B, Zeiner K, Nativel A, Kaniusas E. Auricular vagus nerve stimulator for closed-loop biofeedback-based operation. Analog Integr Circuits Signal Process. 2022;112(2):237-246. doi: 10.1007/s10470-022-02037-8. Epub 2022 May 10.

  PMID: 35571976 BACKGROUND

• Joshi S, Li Y, Kalwani RM, Gold JI. Relationships between Pupil Diameter and Neuronal Activity in the Locus Coeruleus, Colliculi, and Cingulate Cortex. Neuron. 2016 Jan 6;89(1):221-34. doi: 10.1016/j.neuron.2015.11.028. Epub 2015 Dec 17.

  PMID: 26711118 BACKGROUND

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Adjunct Professor at the Department of Health Sciences and Technology and Co-Director of the Rehabilitation Engineering Laboratory

Model Details: Single-blinded, pseudo-randomised, exploratory, single-centre, national, longitudinal study

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 5, 2024
• Study Start: May 14, 2024
• Primary Completion: January 1, 2025
• Study Completion: April 1, 2025
• Last Updated: October 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)