Abstract
Several previous studies have highlighted the potential of transcutaneous vagus nerve stimulation (tVNS) to enhance executive control of action. In the present study, we tested for effects of tVNS on behavioral performance and frontal midline theta activity during response conflicts. Frontal midline theta reflects transient activation of the posterior midfrontal cortex in situations requiring increased executive control of action. It is an established marker for top-down action control. We carried out a combined behavioral and electroencephalography (EEG) within-subjects experimental study employing a cued go–no-go-change task. Twenty-two healthy young adults participated. We found that tVNS enhanced global behavioral accuracy, i.e., decreased the proportion of erroneous and missed responses, compared with sham (placebo) stimulation, and reduced conflict costs on behavioral performance in go/change response conflicts. Furthermore, in trials eliciting go/stop conflicts, frontal midline theta was enhanced under tVNS. These findings corroborate the potential of tVNS to enhance executive control of action. For the first time, we show an effect of tVNS on frontal midline theta activity, which suggests that tVNS specifically interacts with the neural mechanisms underlying action control. We conclude that tVNS is a promising method to enhance executive control and recommend the further investigation of tVNS as a candidate treatment of clinically relevant executive control deficits.
This is a preview of subscription content, access via your institution.


References
Asada, H., Fukuda, Y., Tsunoda, S., Yamaguchi, M., & Tonoike, M. (1999). Frontal midline theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex in humans. Neuroscience Letters, 274(1), 29–32.
Aston-Jones, G., & Cohen, J. D. (2005). An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance. Annual Review of Neuroscience, 28, 403–450.
Baayen, R. H., Davidson, D. J., & Bates, D. M. (2008). Mixed-effects modeling with crossed random effects for subjects and items. Journal of Memory and Language, 59(4), 390–412.
Barr, D. J., Levy, R., Scheepers, C., & Tily, H. J. (2013). Random effects structure for confirmatory hypothesis testing: keep it maximal. Journal of Memory and Language, 68(3), 255–278.
Bates, D., Mächler, M., Bolker, B., & Walker, S. (2015). Fitting linear mixed-effects models using lme4. Journal of Statistical Software, 67(1), 48.
Bauer, S., Baier, H., Baumgartner, C., Bohlmann, K., Fauser, S., Graf, W., et al. (2016). Transcutaneous Vagus Nerve Stimulation (tVNS) for treatment of drug-resistant epilepsy: a randomized, double-blind clinical trial (cMPsE02). Brain Stimulation, 9(3), 356–363.
Baumeister, R. F. (2002). Ego depletion and self-control failure: an energy model of the self’s executive function. Self and Identity, 1(2), 129–136.
Ben-Menachem, E., Hamberger, A., Hedner, T., Hammond, E. J., Uthman, B. M., Slater, J., et al. (1995). Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures. Epilepsy Research, 20(3), 221–227.
Bermejo, P., López, M., Larraya, I., Chamorro, J., Cobo, J. L., Ordóñez, S., et al. (2017). Innervation of the human cavum conchae and auditory canal: anatomical basis for transcutaneous auricular nerve stimulation. BioMed Research International, 2017, 7830919.
Beste, C., Steenbergen, L., Sellaro, R., Grigoriadou, S., Zhang, R., Chmielewski, W., et al. (2016). Effects of Concomitant Stimulation of the GABAergic and Norepinephrine System on Inhibitory Control ??? A Study Using Transcutaneous Vagus Nerve Stimulation. Brain Stimulation, 9(6), 811–818.
Borovikova, L.V., Ivanova, S., Zhang, M., Yang, H., Botchkina, G.I., Watkins, L.R., et al. (2000). Vagus nerve stimulation attenuates the systemic in¯ammatory response to endotoxin. 405, 5.
Botvinick, M. M., Cohen, J. D., & Carter, C. S. (2004). Conflict monitoring and anterior cingulate cortex: an update. Trends in Cognitive Sciences, 8(12), 539–546.
Broncel, A., Bocian, R., Kłos-Wojtczak, P., & Konopacki, J. (2018). Medial septal cholinergic mediation of hippocampal theta rhythm induced by vagal nerve stimulation. PLoS ONE, 13(11), e0206532.
Broncel, A., Bocian, R., Kłos-Wojtczak, P., & Konopacki, J. (2019). GABAergic mediation of hippocampal theta rhythm induced by stimulation of the vagal nerve. Brain Research Bulletin, 147, 110–123.
Brown, T. E., & Landgraf, J. M. (2010). Improvements in executive function correlate with enhanced performance and functioning and health-related quality of life: evidence from 2 large, double-blind, randomized, placebo-controlled trials in ADHD. Postgraduate Medicine, 122(5), 42–51.
Capone, F., Assenza, G., Di Pino, G., Musumeci, G., Ranieri, F., Florio, L., et al. (2015). The effect of transcutaneous vagus nerve stimulation on cortical excitability. Journal of Neural Transmission, 122(5), 679–685.
Cavanagh, J. F., & Frank, M. J. (2014). Frontal theta as a mechanism for cognitive control. Trends in Cognitive Sciences, 18(8), 414–421.
Cavanagh, J. F., & Shackman, A. J. (2015). Frontal midline theta reflects anxiety and cognitive control: Meta-analytic evidence. Journal of Physiology, Paris, 109(1), 3–15.
Cavanagh, J. F., Frank, M. J., Klein, T. J., & Allen, J. J. B. (2010). Frontal theta links prediction errors to behavioral adaptation in reinforcement learning. NeuroImage., 49(4), 3198–3209.
Cavanagh, J. F., Zambrano-Vazquez, L., & Allen, J. J. B. (2012). Theta lingua franca: a common mid-frontal substrate for action monitoring processes. Psychophysiology, 49(2), 220–238.
Cavanagh, J. F., Eisenberg, I., Guitart-Masip, M., Huys, Q., & Frank, M. J. (2013). Frontal Theta Overrides Pavlovian Learning Biases. The Journal of Neuroscience, 33(19), 8541–8548.
Chakravarthy, K., Chaudhry, H., Williams, K., & Christo, P. J. (2015). Review of the uses of vagal nerve stimulation in chronic pain management. Current Pain and Headache Reports, 19(12), 54.
Cohen, M. X. (2014). A neural microcircuit for cognitive conflict detection and signaling. Trends in Neurosciences, 37(9), 480–490.
Cohen, M. X., & Donner, T. H. (2013). Midfrontal conflict-related theta-band power reflects neural oscillations that predict behavior. Journal of Neurophysiology, 110(12), 2752–2763.
Cotrena, C., Branco, L. D., Shansis, F. M., & Fonseca, R. P. (2016). Executive function impairments in depression and bipolar disorder: association with functional impairment and quality of life. Journal of Affective Disorders, 190, 744–753.
Fischer, R., Ventura-Bort, C., Hamm, A., & Weymar, M. (2018a Aug). Transcutaneous vagus nerve stimulation (tVNS) enhances conflict-triggered adjustment of cognitive control. Cognitive, Affective, & Behavioral Neuroscience, 18(4), 680–693.
Fischer, A. G., Nigbur, R., Klein, T. A., Danielmeier, C., & Ullsperger, M. (2018b). Cortical beta power reflects decision dynamics and uncovers multiple facets of post-error adaptation. Nature Communications, 9(1), 5038.
Frangos, E., Ellrich, J., & Komisaruk, B. R. (2015). Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimulation, 8(3), 624–636.
Frank, M. J., Woroch, B. S., & Curran, T. (2005). Error-related negativity predicts reinforcement learning and conflict biases. Neuron, 47(4), 495–501.
Frömer, R., Maier, M., & Rahman, R. A. (2018). Group-level EEG-processing pipeline for flexible single trial-based analyses including linear mixed models. Frontiers in Neuroscience, 12, 48.
Gevins, A. (1997). High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cerebral Cortex, 7(4), 374–385.
Greene, J. D., Hodges, J. R., & Baddeley, A. D. (1995). Autobiographical memory and executive function in early dementia of Alzheimer type. Neuropsychologia, 33(12), 1647–1670.
Hajihosseini, A., & Holroyd, C. B. (2013). Frontal midline theta and N200 amplitude reflect complementary information about expectancy and outcome evaluation: Frontal theta and N200 provide distinct information. Psychophysiology., 50(6), 550–562.
Hall, S.D., Barnes, G.R., Furlong, P.L., Seri, S., Hillebrand, A. (2009). Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco-magnetoencephalography. Human Brain Mapping, n/a–n/a.
Hein, E., Nowak, M., Kiess, O., Biermann, T., Bayerlein, K., Kornhuber, J., et al. (2013). Auricular transcutaneous electrical nerve stimulation in depressed patients: A randomized controlled pilot study. Journal of Neural Transmission, 120(5), 821–827.
Hofmann, W., Schmeichel, B. J., & Baddeley, A. D. (2012). Executive functions and self-regulation. Trends in Cognitive Sciences, 16(3), 174–180.
Hornberger, M., Piguet, O., Kipps, C., & Hodges, J. R. (2008). Executive function in progressive and nonprogressive behavioral variant frontotemporal dementia. Neurology, 71(19), 1481–1488.
Hsieh, L.-T., Ranganath, C. (2014). Frontal midline theta oscillations during working memory maintenance and episodic encoding and retrieval. NeuroImage, 85(0 2). [cited 2019 Apr 10]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859771/.
Hyvärinen, A., & Oja, E. (2000). Independent component analysis: algorithms and applications. Neural Networks, 13(4–5), 411–430.
Jaeger, T. F. (2008). Categorical data analysis: away from ANOVAs (transformation or not) and towards logit mixed models. Journal of Memory and Language, 59(4), 434–446.
Keute, M., Ruhnau, P., Heinze, H.-J., Zaehle, T. (2018a). Behavioral and electrophysiological evidence for GABAergic modulation through transcutaneous vagus nerve stimulation. Clinical Neurophysiology.
Keute, M., Ruhnau, P., & Zaehle, T. (2018b). Reply to “Reconsidering sham in transcutaneous vagus nerve stimulation studies”. Clin Neurophysiol Off J Int Fed Clin Neurophysiol., 129(11), 2503.
Klimesch, W. (1999). EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis. Brain Research Reviews, 29(2), 169–195.
Lehtimäki, J., Hyvärinen, P., Ylikoski, M., Bergholm, M., Mäkelä, J. P., Aarnisalo, A., et al. (2013). Transcutaneous vagus nerve stimulation in tinnitus: a pilot study. Acta Otolaryngol (Stockh)., 133(4), 378–382.
Lesh, T. A., Westphal, A. J., Niendam, T. A., Yoon, J. H., Minzenberg, M. J., Ragland, J. D., et al. (2013). Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia. NeuroImage Clinical, 2, 590–599.
Liebrand, M., Kristek, J., Tzvi, E., & Krämer, U. M. (2018). Ready for change: oscillatory mechanisms of proactive motor control. PLoS One, 13(5), e0196855.
Logan, G. D. (1985). Executive control of thought and action. Acta Psychologica, 60(2–3), 193–210.
Luu, P., Tucker, D. M., & Makeig, S. (2004). Frontal midline theta and the error-related negativity: neurophysiological mechanisms of action regulation. Clinical Neurophysiology, 115(8), 1821–1835.
Manard, M., François, S., Phillips, C., Salmon, E., & Collette, F. (2017). The neural bases of proactive and reactive control processes in normal aging. Behavioural Brain Research, 320, 504–516.
McKinlay, A., Grace, R. C., Dalrymple-Alford, J. C., & Roger, D. (2010). Characteristics of executive function impairment in Parkinson’s disease patients without dementia. Journal of the International Neuropsychological Society, 16(2), 268–277.
Mitchell, D. J., McNaughton, N., Flanagan, D., & Kirk, I. J. (2008). Frontal-midline theta from the perspective of hippocampal “theta”. Progress in Neurobiology, 86(3), 156–185.
Ness, K. K., Gurney, J. G., Zeltzer, L. K., Leisenring, W., Mulrooney, D. A., Nathan, P. C., et al. (2008). The impact of limitations in physical, executive, and emotional function on health-related quality of life among adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Archives of Physical Medicine and Rehabilitation, 89(1), 128–136.
Nichols, J. A., Nichols, A. R., Smirnakis, S. M., Engineer, N. D., Kilgard, M. P., & Atzori, M. (2011). Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors. Neuroscience, 189, 207–214.
Nigbur, R., Ivanova, G., & Stürmer, B. (2011). Theta power as a marker for cognitive interference. Clinical Neurophysiology, 122(11), 2185–2194.
Onton, J., Delorme, A., & Makeig, S. (2005). Frontal midline EEG dynamics during working memory. Clinical Neurophysiology, 27(2), 341–356.
Oostenveld, R., Fries, P., Maris, E., & Schoffelen, J.-M. (2011). FieldTrip: open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data. Computational Intelligence and Neuroscience, 2011, 1.
Ozonoff, S., & Jensen, J. (1999). Brief report: Specific executive function profiles in three neurodevelopmental disorders. Journal of Autism and Developmental Disorders, 29(2), 171–177.
Peuker, E. T., & Filler, T. J. (2002). The nerve supply of the human auricle. Clinical Anatomy, 15(1), 35–37.
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012). Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron., 76(1), 116–129.
Pinner, J. F. L., & Cavanagh, J. F. (2017). Frontal theta accounts for individual differences in the cost of conflict on decision making. Brain Research, 1672, 73–80.
Posner, M. I., Snyder, C. R., & Solso, R. (2004). Attention and cognitive control. Cognitive Psychology Key Read, 205.
Quetscher, C., Yildiz, A., Dharmadhikari, S., Glaubitz, B., Schmidt-Wilcke, T., Dydak, U., et al. (2015). Striatal GABA-MRS predicts response inhibition performance and its cortical electrophysiological correlates. Brain Structure & Function, 220(6), 3555–3564.
Raedt, R., Clinckers, R., Mollet, L., Vonck, K., Tahry, R. E., Wyckhuys, T., et al. (2011). Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. Journal of Neurochemistry, 117(3), 461–469.
Sellaro, R., van Leusden, J. W. R., Tona, K.-D., Verkuil, B., Nieuwenhuis, S., & Colzato, L. S. (2015). Transcutaneous vagus nerve stimulation enhances post-error slowing. Journal of Cognitive Neuroscience, 27(11), 2126–2132.
Sherman, E. M. S., Slick, D. J., & Eyrl, K. L. (2006). Executive dysfunction is a significant predictor of poor quality of life in children with epilepsy. Epilepsia, 47(11), 1936–1942.
Skirrow, C., McLoughlin, G., Banaschewski, T., Brandeis, D., Kuntsi, J., & Asherson, P. (2015). Normalisation of frontal theta activity following methylphenidate treatment in adult attention-deficit/hyperactivity disorder. European Neuropsychopharmacology, 25(1), 85–94.
Steenbergen, L., Sellaro, R., Stock, A. K., Verkuil, B., Beste, C., & Colzato, L. S. (2015). Transcutaneous vagus nerve stimulation (tVNS) enhances response selection during action cascading processes. European Neuropsychopharmacology, 25(6), 773–778.
Ventura-Bort, C., Wirkner, J., Genheimer, H., Wendt, J., Hamm, A.O., Weymar, M. (2018). Effects of transcutaneous vagus nerve stimulation (tVNS) on the P300 and Alpha-amylase level: a pilot study. Frontiers in Human Neuroscience. [cited 2019 Mar 15];12. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021745/.
Wang, C.-H., Lo, Y.-H., Pan, C.-Y., Chen, F.-C., Liang, W.-K., & Tsai, C.-L. (2015). Frontal midline theta as a neurophysiological correlate for deficits of attentional orienting in children with developmental coordination disorder. Psychophysiology, 52(6), 801–812.
Warren, C. M., Tona, K. D., Ouwerkerk, L., Van Paridon, J., Poletiek, F., van Steenbergen, H., et al. (2019). The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Brain Stimulation, 12(3), 635–642.
Weinstein, A. M., Voss, M. W., Prakash, R. S., Chaddock, L., Szabo, A., White, S. M., et al. (2012). The association between aerobic fitness and executive function is mediated by prefrontal cortex volume. Brain, Behavior, and Immunity, 26(5), 811–819.
Willcutt, E. G., Doyle, A. E., Nigg, J. T., Faraone, S. V., & Pennington, B. F. (2005). Validity of the executive function theory of attention-deficit/hyperactivity disorder: a meta-analytic review. Biological Psychiatry, 57(11), 1336–1346.
Yakunina, N., Kim, S. S., & Nam, E.-C. (2017). Optimization of transcutaneous vagus nerve stimulation using functional MRI. Neuromodulation Technol Neural Interface, 20(3), 290–300.
Zeng, Q., Qi, S., Li, M., Yao, S., Ding, C., & Yang, D. (2017). Enhanced conflict-driven cognitive control by emotional arousal, not by valence. Cognition & Emotion, 31(6), 1083–1096.
Funding
The work was funded by the Deutsche Forschungsgemeinschaft Sonderforschungsbereich Grant, SFB-779, TPA02, and the federal state of Saxony-Anhalt and the “European Regional Development Fund“ (ERDF 2014-2020), Vorhaben: Center for Behavioral Brain Sciences (CBBS), FKZ: ZS/2016/04/78113.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no competing interests.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 1728 kb)
Rights and permissions
About this article
Cite this article
Keute, M., Barth, D., Liebrand, M. et al. Effects of Transcutaneous Vagus Nerve Stimulation (tVNS) on Conflict-Related Behavioral Performance and Frontal Midline Theta Activity. J Cogn Enhanc 4, 121–130 (2020). https://doi.org/10.1007/s41465-019-00152-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s41465-019-00152-5
Keywords
- tVNS
- EEG
- Executive control
- Response conflict
- Frontal midline theta