Noninvasive Transcutaneous Vagus Nerve Stimulation for Epilepsy
Epilepsy Reconsidered
Vagus nerve stimulation (VNS) has been used for decades to treat drug-resistant epilepsy. Surgically implanted VNS is an established adjunctive treatment, while non-invasive transcutaneous auricular VNS (taVNS) is a promising approach with a growing, but less established, clinical evidence base. Today, VNS is safer, more accessible than in the past. At the same time, our understanding of epilepsy has advanced, leading to new approaches that can improve seizure control and quality of life. We are entering a new era in epilepsy treatment that offers renewed hope for many people living with seizures.
Allow me to explain. If you live with epilepsy, you may have been told that a seizure is like a “short circuit” in the brain. It’s a convenient analogy, and it captures something real—but it misses the true nature of the condition.
Importantly, epilepsy is much more than a disorder of abnormal electrical activity. Seizure expression is shaped by multiple physiological processes, including sleep, neuroinflammation, autonomic function, and large-scale brain network dynamics. This is clearly demonstrated by a substantial body of research. That perspective tells us that epilepsy is a disorder arising from dysregulated brain and body systems, rather than a purely electrical problem.
Brain function depends on coordinated activity across complex, interconnected networks. In epilepsy, instability within these systems contributes to seizure vulnerability. This means that seizure occurrence is not determined solely by the presence of abnormal electrical activity, but by how stable and well-regulated the broader neural network is at any given time.
This leads to a different way of understanding seizures: Seizures are expressions of a neurological system that has lost its stability.
Beyond “Electrical Short Circuits”: Regulation, Sleep, Inflammation, and Seizure Control
There is more to epilepsy than simply abnormal electrical activity in the brain. When we focus solely on the electrical problem, we miss multiple opportunities to treat epilepsy. That’s why the narrow electrical perspective is clinically limiting.
Epilepsy is also a disorder of regulation. Seizures emerge within a wider physiological context that includes sleep quality, circadian timing, autonomic function, inflammatory signalling, network stability, and the brain’s ability to maintain organised activity under stress. Furthermore, this perspective fits clinical reality. Patients recognise that poor sleep, physiological overload, and instability make seizures more likely. Contemporary research supports that intuition and shows that epilepsy cannot be understood adequately if it is reduced to “electrical short circuits” alone (Bonilla-Jaime et al., 2021). (See the complete reference list at the end of this page.)
Within that broader framework, vagus nerve stimulation (VNS) becomes easier to understand. It is not simply a device that suppresses seizures. It is a neuromodulatory intervention that acts on systems of physiological regulation. VNS influences autonomic function, engages central vagal pathways, modulates neurotransmitter systems, affects large-scale brain networks, and has documented anti-inflammatory benefits. That matters because seizure control depends not only on reducing abnormal discharges, but also on restoring the stability of the system in which those discharges occur (Krahl, 2012; Krahl & Clark, 2012; Leung, 2017). In this sense, effective treatment is not only about suppressing abnormal activity, but about improving the conditions under which the brain can maintain organised, stable function.
Seizures are a symptom of problems within the brain. If treatment is going to be effective in the long-term, we need to do more than suppress the symptoms; we need to address the underlying causes. And doing so is a complex challenge that requires an expanded perspective on the problem.
Section 1: For Patients, General Readers and Doctors
Understanding epilepsy more fully
For many patients, anti-seizure medication works well. However, around 20–30% of patients develop drug-resistant epilepsy, meaning seizures continue despite appropriate treatment. For these individuals, it is not enough simply to keep adding medication. A more layered and physiologically informed approach is required (Panebianco et al., 2022).
One of the most important things to understand is that sleep is not a minor issue in epilepsy. It is central. Sleep disturbances are disproportionately common in people with epilepsy, and poor sleep quality is associated with increased seizure frequency, worsening disease course, and reduced quality of life. The scientific literature also makes clear that a substantial proportion of seizures occur during sleep, and that sleep-related mechanisms are relevant to epilepsy-related mortality as well (Bonilla-Jaime et al., 2021).
This is not a controversial or novel idea in the basic sense. Clinicians have long known that sleep deprivation can precipitate seizures. What is newer is the way we now understand this relationship. Sleep disruption is not merely a trigger that sits outside the condition. Sleep participates in the biology of epilepsy itself. The evidence suggests that neuroinflammation may be a key mechanistic link between disordered sleep and worsening epilepsy, helping to explain why unstable sleep can amplify seizure vulnerability and disease progression (Bonilla-Jaime et al., 2021). This is a crucial insight.
What is VNS?
Vagus nerve stimulation is a form of neuromodulation. It works by stimulating the vagus nerve, which is one of the major communication pathways linking the body and the brain. VNS has been an established treatment for drug-resistant epilepsy for many years. Surgically implanted VNS for treatment for epilepsy was approved by the FDA in 1997 (Krahl, 2012; Krahl & Clark, 2012).
There are two main forms of VNS relevant here. The traditional form is invasive VNS, in which a device is implanted surgically and attached to the left cervical vagus nerve. The newer form is transcutaneous auricular VNS, or taVNS, in which stimulation is delivered non-invasively through the auricular branch of the vagus nerve in the ear. The importance of taVNS is that it accesses central vagal pathways without requiring surgery (He et al., 2013; von Wrede et al., 2021).
How effective is VNS?
VNS is not a cure for epilepsy, but it is a meaningful treatment option in refractory cases, i.e. those patients with a poor response to medication. Reviews of invasive VNS show that approximately 20–40% of patients achieve a 50% or greater reduction in seizure frequency, and response often improves over time rather than appearing all at once (Krahl, 2012; Krahl & Clark, 2012).
Transcutaneous VNS is also increasingly promising. A randomized controlled trial in refractory epilepsy reported seizure reduction and improvement in quality of life with taVNS, while a separate randomized double-blind trial found the treatment was well tolerated and that the results justified further and larger trials (Aihua et al., 2014; Bauer et al., 2016; Hamer & Bauer, 2019).
Particularly striking is a recent long-term retrospective cohort comparing invasive and transcutaneous VNS. In that study, response rates over five years were comparable, adverse effects were few and mild with both methods, and quality of life improved significantly. The authors concluded that both invasive and non-invasive approaches were effective, well-tolerated treatments for drug-resistant epilepsy (Weyand et al., 2026).
Why sleep matters so much
If there is one idea that deserves to be made explicit, it is this: sleep is mechanistically central to seizure control. Sleep disruption is not just a nuisance. It affects neuronal excitability, inflammatory signalling, blood–brain barrier integrity, stress systems, and the stability of brain networks. A recent review makes it clear that epilepsy patients with poor sleep quality have intensified seizure frequency and disease progression. Neuroinflammation caused by sleep disruption seems to synergise with seizure-related neuroinflammation to worsen injury in the epileptic brain (Bonilla-Jaime et al., 2021).
That is exactly why a regulation-based approach matters. If a person’s sleep is unstable, if their physiology is chronically stressed, if inflammatory signalling is heightened, and if the brain is being repeatedly pushed toward dysregulation, then seizure control becomes more difficult. Conversely, when sleep is improved and the broader physiology is stabilised, the whole system becomes more resilient. This is not an alternative to medical treatment. It is part of a more complete, rational and scientifically credible understanding of epilepsy (Bonilla-Jaime et al., 2021).
Sleep apnoea: a common and treatable contributor to seizures
A particularly important and often under-recognised contributor to seizure burden is obstructive sleep apnoea (OSA). OSA is more common in people with epilepsy than in the general population. A meta-analysis estimated that approximately one-third of people with epilepsy have mild-to-severe OSA, although prevalence varies across populations and diagnostic criteria (Lin et al., 2017).
Several mechanisms may help explain how sleep apnoea influences seizure vulnerability. Repeated sleep fragmentation and intermittent oxygen deprivation can affect neuronal excitability and autonomic regulation. These disturbances may make seizure control more difficult (Manni & Terzaghi, 2010).
Treatment of coexisting OSA has been associated with improved seizure control. Prospective pilot work and a meta-analysis support the potential benefit of identifying and treating OSA in people with epilepsy, although the magnitude of improvement varies and the available evidence does not guarantee a particular outcome for an individual patient (Malow et al., 2003; Lin et al., 2017).
Identifying and treating sleep apnoea therefore represents a practical opportunity to address a potentially modifiable contributor to seizure burden, alongside standard epilepsy treatment.
This is why we actively target sleep apnoea at Ormond Neuroscience. These findings also provide a useful context for understanding interventions we use, such as VNS, which act on autonomic and regulatory systems that overlap with those systems affected in sleep apnoea.
Where VNS fits in this broader picture
This is where VNS becomes especially interesting. VNS should not be thought of narrowly as a seizure-suppressing device. VNS acts on the physiology of regulation. It engages afferent vagal pathways, influences the nucleus tractus solitarius, reaches neuromodulatory systems such as the locus coeruleus and raphe nuclei, alters network dynamics, and is linked to anti-inflammatory effects and restoration of vagal tone (Krahl, 2012; Krahl & Clark, 2012; Leung, 2017).
That means taVNS sits naturally inside a overarching model of epilepsy management that includes sleep, autonomic regulation, inflammation, rehabilitation, and environmental stability. At Ormond Neuroscience, that broader model is what we call Neuroharmonics, our brain treatment programme. Within that framework, taVNS is not seen as a standalone cure. Instead, it is a powerful tool for helping the brain to become more stable, more adaptive, and more capable of regulating itself.
This reflects a shift in emphasis from targeting seizures as isolated events to supporting the physiological systems that determine whether those events occur in the first place.
Sleep and sleep apnoea are important treatment targets of the Neuroharmonics treatment programme. taVNS provides a means of directly stimulating specific regulatory nuclei in the brain, such as the nucleus tractus solitarius (NTS).
Safety and tolerability
The distinction between invasive VNS and taVNS is especially important when discussing side effects. Invasive VNS can produce hoarseness, cough, dysphagia, throat discomfort, and dyspnoea. These effects are well known and arise because implanted stimulation at the cervical vagal trunk can influence branches related to laryngeal and other peripheral functions (Krahl, 2012; Panebianco et al., 2022). Implanted VNS can also worsen sleep-disordered breathing, so new or worsening snoring, witnessed apnoeas, or daytime sleepiness warrants assessment (Kim et al., 2022).
taVNS is different. In the recent comparative cohort, hoarseness, cough, dyspnoea, and dysphagia were reported in the invasive group but not in the transcutaneous group, whereas taVNS adverse effects were mainly local and mild, such as paresthesia, pain, erythema (rash), skin irritation, or a feeling of pressure (Weyand et al., 2026). This is a legitimate clinical advantage of the non-invasive taVNS approach.
Efficacy of taVNS
Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising non-invasive approach to seizure reduction, particularly in patients with drug-resistant epilepsy. Randomised controlled trials and controlled studies have demonstrated that taVNS can produce clinically meaningful reductions in seizure frequency when used as an adjunctive therapy.
In a recent double-blind, controlled trial, active taVNS was associated with significant reductions in seizure frequency compared to control stimulation over a 20-week treatment period (Yang et al., 2023). A systematic review and meta-analysis also reported higher responder rates with auricular stimulation than with control treatment, although the included interventions and studies were heterogeneous (Zhang et al., 2024). Earlier controlled trials in drug-resistant epilepsy similarly demonstrated that taVNS can significantly reduce seizure frequency and severity compared to sham stimulation (Aihua et al., 2014).
Together, these findings support taVNS as a promising adjunctive approach to drug-resistant epilepsy. Results vary across studies, and further well-designed trials are needed to establish its effectiveness, optimal treatment protocols, and durability of benefit (Bauer et al., 2016; Yang et al., 2023; Zhang et al., 2024). At Ormond Neuroscience, we use taVNS within our Neuroharmonics treatment programme that targets physiological regulation.
The Ormond Neuroscience Experience
It’s worth mentioning our own experience at Ormond Neuroscience with taVNS. With one patient who was having 1-3 tonic-clonic epileptic seizures a week, we have been able to reduce his seizure frequency to approximately one seizure every 4-6 weeks using taVNS embedded within the Neuroharmonics treatment program. Furthermore, the severity of the seizures has changed significantly. When he first came to us, his seizures involved loss of consciousness and convulsions, whereas nowadays he experiences a transient loss of awareness and brief speech difficulties. The convulsions are gone and the complete loss of consciousness is now history.
Importantly, there was a stage when we thought we could reduce the daily duration of taVNS, but when we did this, his seizures returned. When we returned the stimulation duration and intensity to the original treatment regime, his seizures were again abolished. That was a tough learning experience but reinforced how effective taVNS can be. In his situation, the use of taVNS has been transformative and has made a massive difference to the quality of his life.
Section 2: For Healthcare Professionals
Epilepsy as a disorder of regulation
As discussed above, while seizures are electrophysiological events, seizure vulnerability is influenced by broader physiological processes, including sleep, inflammation, autonomic balance, and neuromodulatory tone. Sleep disruption may worsen epilepsy through neuroinflammatory mechanisms, reinforcing the importance of assessing and managing sleep disturbances as part of epilepsy care (Bonilla-Jaime et al., 2021).
Mechanisms of VNS
Eighty percent of vagal fibres are afferent and project primarily to the nucleus tractus solitarius, which functions as a major relay for visceral and sensory input. From there, the NTS projects directly or indirectly to multiple structures relevant to seizure modulation, including the locus coeruleus, raphe nuclei, hypothalamic nuclei, amygdala, thalamic regions, and distributed cortical systems (Krahl, 2012; Krahl & Clark, 2012). Thus, VNS targets include:
- Nucleus tractus solitarius as the primary vagal relay and which modulates both excitatory glutamate pathways and inhibitory GABA pathways
- Locus coeruleus and noradrenergic modulation
- Raphe nuclei and serotonergic modulation
- Limbic and thalamic projections
- Distributed cortical and network-level effects
This matters because the clinical effect of VNS is not local but rather systems-level. In epilepsy, that includes altered excitability, seizure threshold modulation, network desynchronisation and stabilisation, and longer-term plastic effects. A small MRI pilot study in patients with drug-resistant epilepsy found associations between VNS treatment response and features of the locus coeruleus and its connections with the hippocampus. These exploratory findings support a possible role for noradrenergic modulation and neuroplasticity in VNS treatment, but do not yet establish a validated predictor of treatment response (Berger et al., 2024).
EEG and network studies reinforce the same point. Responders to VNS have shown reduced interictal cortical synchrony, suggesting that desynchronisation may be part of the anti-seizure effect, while taVNS has been shown to induce stabilising modifications in large-scale functional brain networks consistent with greater resilience and stability (Bodin et al., 2015; von Wrede et al., 2021).
Autonomic and inflammatory regulation
Vagus nerve stimulation influences systems involved in autonomic and inflammatory regulation. Research has identified changes in autonomic measures and immune signalling following VNS, including changes in some circulating cytokines (Leung, 2018). These findings are relevant to epilepsy, where seizures and associated physiological stressors can interact with inflammatory processes. Autonomic and inflammatory changes are therefore potential contributors to the therapeutic effects of VNS, although their contribution to seizure reduction in humans remains to be established.
The relationship between sleep, inflammation, and epilepsy further reinforces this perspective. Both seizures and sleep disruption are associated with increased neuroinflammatory activity, including activation of glial cells and the release of pro-inflammatory mediators. Emerging evidence suggests that sleep disruption may act as an additional “second hit,” amplifying seizure susceptibility and contributing to disease progression through inflammatory mechanisms (Bonilla-Jaime et al., 2021).
Within this framework, epilepsy is conceptualised as a condition in which multiple physiological systems interact to influence seizure vulnerability. From this perspective, seizure frequency and severity reflect the dynamic state of these interacting systems, rather than a fixed property of the underlying pathology alone. VNS is therefore relevant not only because it can reduce seizure frequency, but because it acts on core regulatory systems—autonomic state, neuromodulatory tone, inflammatory signalling, sleep stability, and large-scale network organisation—that together determine whether the brain moves toward instability or resilience.
Transcutaneous VNS in this framework
taVNS fits especially well within this model. Mechanistically, stimulation of the auricular branch of the vagus nerve can engage central vagal circuitry, including pathways involving the nucleus tractus solitarius (NTS). In rats, He et al. (2013) demonstrated an auriculo-vagal afferent pathway and found that auricular stimulation suppressed epileptiform activity. This effect was weakened by a reversible cooling block of the NTS, supporting its involvement in seizure suppression in that experimental model. These findings provide mechanistic support for the biological plausibility of taVNS in epilepsy, while the extent to which the same mechanisms explain clinical benefits in humans remains under investigation.
Clinically, taVNS also avoids the characteristic laryngeal side effects of implanted VNS (hoarseness, cough, dyspnoea, and dysphagia), while overall efficacy, quality-of-life impact, and patient willingness to choose treatment again were comparable over five years (Weyand et al., 2026).
Mood, quality of life, and cognition
A balanced account of the broader effects of vagus nerve stimulation (VNS) remains important. Beyond seizure reduction, VNS is associated with improvements in mood and quality of life, some of which may occur independently of improvements in seizure control. Evidence for cognitive benefits has also strengthened, particularly with non-invasive transcutaneous auricular VNS (taVNS). A recent systematic review and meta-analysis reported cognitive benefits associated with taVNS, particularly in executive functioning, cognitive flexibility and learning, with smaller improvements in attention and working memory (Liu & Li, 2026). Encouraging findings have also emerged from controlled studies involving mild cognitive impairment (MCI), including improvements in global cognition accompanied by changes in functional brain network connectivity (Xu et al., 2026). These results strengthen the evidence for cognitive benefits in selected settings, but do not yet establish comparable improvements in patients with epilepsy. An epilepsy-specific systematic review and meta-analysis did not establish consistent improvements in overall cognitive performance (Kong et al., 2024). Cognitive outcomes may vary with the clinical population, stimulation protocol and duration of treatment, and further controlled studies are needed to establish the magnitude and durability of benefit. VNS therefore has promising applications beyond seizure control, while its cognitive benefits in epilepsy remain less certain.
Neuroharmonics and epilepsy
The Neuroharmonics framing helps to make the deep structure of the problem explicit. Epilepsy is not only about discharges. It is about dysregulation. Sleep instability, inflammatory burden, autonomic imbalance, physiological stress, and network fragility all influence whether a brain is pushed toward seizure expression or toward resilience. VNS belongs within this framework because it acts at the level of regulation. It modulates systems that stabilise the brain rather than merely suppressing symptoms in a narrow sense.
That is why the sleep story matters so much. It is not a side issue. It is one of the clearest windows into the physiology of epilepsy. Once sleep, inflammation, and autonomic regulation are brought into view, the condition becomes more intelligible, the patient’s experience makes more sense, and treatment moves beyond simplistic explanations toward a layered and scientifically credible model of care.
At Ormond Neuroscience, our approach to using vagus nerve stimulation for epilepsy uses a model with a rational and focused approach to neural regulation via multiple physiological systems. taVNS is a vital component of a broader treatment regime.
Get in Touch
If you would like to explore whether vagus nerve stimulation is appropriate for your situation, please get in touch to arrange an interview.
Learn More
If you’ve wondered about the terminology, “vagus” is a noun referring to the nerve itself, whereas “vagal” is an adjective referring to things related to the nerve, such as vagal pathways, vagal modulation, or the commonly used (but strictly incorrect) phrase “vagal nerve stimulation.”
For further information about vagus nerve stimulation and its clinical applications, please see the following pages:
Ormond Neuroscience Web Pages
- Vagus Nerve Stimulation (Overview) — general principles and mechanisms
- VNS and Neuroplasticity — how neuromodulation supports learning and recovery
- VNS and Mood & Autonomic Regulation — the role of brain–body regulation in emotional states
- VNS for Stroke and Brain Injury Rehabilitation — application in neurological recovery
- VNS for Epilepsy — clinical use in seizure disorders
- VNS for Autonomic Dysfunction and Stress-Related Conditions (in development).
Talks and Interviews
For those interested in a deeper exploration of the neuroscience and clinical application of VNS, the following talks and interviews provide additional context:
- The Groundbreaking Potential of Vagal Nerve Stimulation. A TEDxJohannesburg presentation exploring the scientific basis of VNS and its application across conditions such as trauma, stroke, and mood disorders.
- Waxing Clinical – Vagal Nerve Stimulation: Neuromodulation for mind-brain health. A clinically focused session on the Netcare Group platform discussing the neurophysiology of VNS and its use in mood disorders and brain regulation. (Tip: content begins at approximately 5 minutes.)
- A holistic approach to brain health. A discussion of VNS within broader brain health strategies, including its relationship to the gut–brain axis and cognitive decline on the Medical Academic platform.
- Cognitive Decline, Dementia, & Neuroplasticity. An overview of VNS in the context of ageing, cognitive decline, and neuroplasticity for Longevity Magazine.
Frequently Asked Questions
What is vagus nerve stimulation (VNS)?
Vagus nerve stimulation is a form of neuromodulation that stimulates the vagus nerve, one of the major communication pathways linking the body and the brain. In epilepsy, VNS is used to help reduce seizure frequency and improve physiological regulation.
Traditional VNS involves surgical implantation of a device attached to the vagus nerve in the neck. Transcutaneous auricular VNS (taVNS) is a non-invasive form that stimulates branches of the vagus nerve through the ear.
Is epilepsy only an electrical disorder?
No. While abnormal electrical activity is central to seizures, epilepsy is increasingly understood as a disorder involving broader systems of regulation, including sleep, autonomic function, inflammation, stress physiology, and large-scale brain network stability.
This broader perspective helps explain why factors such as poor sleep, physiological stress, illness, and autonomic instability can strongly influence seizure frequency.
How does VNS help epilepsy?
VNS does not simply “block seizures.” Rather, it influences regulatory systems involved in autonomic function, arousal, inflammation, neuromodulation, and network stability.
Through pathways involving the nucleus tractus solitarius, locus coeruleus, raphe nuclei, and broader brain networks, VNS may help support the physiological conditions under which the brain becomes more stable and less vulnerable to seizures.
Is transcutaneous auricular VNS (taVNS) effective for epilepsy?
Research increasingly suggests that taVNS can reduce seizure frequency in some patients with drug-resistant epilepsy, particularly when used as part of a broader treatment approach.
Several controlled trials and longer-term cohort studies have reported meaningful seizure reduction, improvement in quality of life, and good tolerability. While results vary between individuals, the overall evidence supports taVNS as a promising adjunctive treatment option.
Does VNS replace anti-seizure medication?
Usually not. VNS is generally used as an adjunctive treatment rather than a replacement for anti-seizure medication.
However, some individuals may eventually reduce medication burden under specialist medical supervision if seizure control improves. Decisions regarding medication should always be made carefully with the treating neurologist or physician.
Why does sleep matter so much in epilepsy?
Sleep is deeply involved in seizure regulation. Poor sleep quality, sleep fragmentation, sleep deprivation, and sleep apnoea can all increase seizure vulnerability.
Research increasingly suggests that sleep disruption contributes to autonomic instability, inflammatory signalling, and impaired network regulation, all of which may make seizures more likely.
Improving sleep is therefore an important part of epilepsy management.
What is the relationship between sleep apnoea and epilepsy?
Obstructive sleep apnoea (OSA) is significantly more common in people with epilepsy than in the general population.
Repeated sleep disruption and intermittent oxygen deprivation can increase autonomic stress, inflammation, and neuronal excitability, lowering seizure threshold. Importantly, treatment of sleep apnoea has been associated with meaningful improvements in seizure control in many patients.
Is taVNS safer than implanted VNS?
taVNS avoids surgery and does not stimulate the cervical vagal trunk directly, so it generally avoids side effects such as hoarseness, cough, throat discomfort, and swallowing difficulties that can occur with implanted VNS.
Most reported taVNS side effects are mild and local, such as tingling, skin irritation, pressure, or temporary discomfort around the ear.
What is Neuroharmonics?
Neuroharmonics is the broader brain treatment programme used at Ormond Neuroscience. It approaches epilepsy as a disorder involving regulation across multiple physiological systems rather than purely abnormal electrical activity alone.
Within this framework, interventions such as taVNS, sleep optimisation, autonomic regulation, rehabilitation, behavioural intervention, and management of physiological stress are integrated into a broader systems-based approach to brain health and seizure control.
Selected References and Further Reading
The following publications provide scientific background on vagus nerve stimulation, epilepsy, sleep, and cognitive outcomes. The supplementary doctoral thesis is identified separately.
Clinical efficacy and tolerability in epilepsy
Aihua, L., Lu, S., Liping, L., Xiuru, W., Hua, L., & Yuping, W. (2014). A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy. Epilepsy & Behavior, 39, 105–110.
Bauer, S., Baier, H., Baumgartner, C., Bohlmann, K., Fauser, S., Graf, W., Hillenbrand, B., Hirsch, M., Last, C., Lerche, H., Mayer, T., Schulze-Bonhage, A., Steinhoff, B. J., Weber, Y., Hartlep, A., Rosenow, F., & Hamer, H. M. (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.
Hamer, H. M., & Bauer, S. (2019). Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Epilepsy Research, 153, 83–84.
Panebianco, M., Rigby, A., & Marson, A. G. (2022). Vagus nerve stimulation for focal seizures. Cochrane Database of Systematic Reviews, 2022(7), Article CD002896.
Cochrane Database of Systematic Reviews
Weyand, A. M., Cordes, N., Linka, L., Strehlau, S., Tsalouchidou, P.-E., Carl, B., Gjorgjevsky, M., Grote, A., Nimsky, C., Möller, L., Habermehl, L., Zahnert, F., Strzelczyk, A., Rosenow, F., Münchberger, C., Hakel, L., Menzler, K., Immisch, I., Krause, K., & Knake, S. (2026). Long-term effects of invasive and transcutaneous vagus nerve stimulation in patients with epilepsy: A retrospective cohort study. Clinical Epileptology, 39, 145–153.
Yang, H., Shi, W., Fan, J., Wang, X., Song, Y., Lian, Y., Shan, W., & Wang, Q. (2023). Transcutaneous auricular vagus nerve stimulation (ta-VNS) for treatment of drug-resistant epilepsy: A randomized, double-blind clinical trial. Neurotherapeutics, 20(3), 870–880.
Zhang, Q., Luo, X., Wang, X.-H., Li, J.-Y., Qiu, H., & Yang, D.-D. (2024). Transcutaneous auricular vagus nerve stimulation for epilepsy. Seizure, 119, 84–91.
Vagal pathways neuromodulation and brain networks
Berger, A., Beckers, E., Joris, V., Duchêne, G., Danthine, V., Delinte, N., Cakiroglu, I., Sherif, S., Morrison, E. I. G., Sánchez, A. T., Macq, B., Dricot, L., Vandewalle, G., & El Tahry, R. (2024). Locus coeruleus features are linked to vagus nerve stimulation response in drug-resistant epilepsy. Frontiers in Neuroscience, 18, Article 1296161.
Bodin, C., Aubert, S., Daquin, G., Carron, R., Scavarda, D., McGonigal, A., & Bartolomei, F. (2015). Responders to vagus nerve stimulation (VNS) in refractory epilepsy have reduced interictal cortical synchronicity on scalp EEG. Epilepsy Research, 113, 98–103.
He, W., Jing, X.-H., Zhu, B., Zhu, X.-L., Li, L., Bai, W.-Z., & Ben, H. (2013). The auriculo-vagal afferent pathway and its role in seizure suppression in rats. BMC Neuroscience, 14, Article 85.
Kaniusas, E., Kampusch, S., Tittgemeyer, M., Panetsos, F., Gines, R. F., Papa, M., Kiss, A., Podesser, B., Cassara, A. M., Tanghe, E., Samoudi, A. M., Tarnaud, T., Joseph, W., Marozas, V., Lukosevicius, A., Ištuk, N., Šarolić, A., Lechner, S., Klonowski, W., … Széles, J. C. (2019). Current directions in the auricular vagus nerve stimulation I – A physiological perspective. Frontiers in Neuroscience, 13, Article 854.
Krahl, S. E. (2012). Vagus nerve stimulation for epilepsy: A review of the peripheral mechanisms. Surgical Neurology International, 3(Suppl. 1), S47–S52.
Surgical Neurology International
Krahl, S. E., & Clark, K. B. (2012). Vagus nerve stimulation for epilepsy: A review of central mechanisms. Surgical Neurology International, 3(Suppl. 4), S255–S259.
Surgical Neurology International
von Wrede, R., Rings, T., Schach, S., Helmstaedter, C., & Lehnertz, K. (2021). Transcutaneous auricular vagus nerve stimulation induces stabilizing modifications in large-scale functional brain networks: Towards understanding the effects of taVNS in subjects with epilepsy. Scientific Reports, 11, Article 7906.
Sleep neuroinflammation and obstructive sleep apnoea
Bonilla-Jaime, H., Zeleke, H., Rojas, A., & Espinosa-Garcia, C. (2021). Sleep disruption worsens seizures: Neuroinflammation as a potential mechanistic link. International Journal of Molecular Sciences, 22(22), Article 12531.
International Journal of Molecular Sciences
Foldvary-Schaefer, N., Andrews, N. D., Pornsriniyom, D., Moul, D. E., Sun, Z., & Bena, J. (2012). Sleep apnea and epilepsy: Who’s at risk?. Epilepsy & Behavior, 25(3), 363–367.
Foldvary-Schaefer, N., & Grigg-Damberger, M. (2006). Sleep and epilepsy: What we know, don’t know, and need to know. Journal of Clinical Neurophysiology, 23(1), 4–20.
Journal of Clinical Neurophysiology
Kim, J. S., Lee, D. E., Bae, H., Song, J. Y., Yang, K. I., & Hong, S. B. (2022). Effects of vagus nerve stimulation on sleep-disordered breathing, daytime sleepiness, and sleep quality in patients with drug-resistant epilepsy. Journal of Clinical Neurology, 18(3), 315–322.
Lin, Z., Si, Q., & Xiaoyi, Z. (2017). Obstructive sleep apnoea in patients with epilepsy: A meta-analysis. Sleep and Breathing, 21(2), 263–270.
Malow, B. A., Weatherwax, K. J., Chervin, R. D., Hoban, T. F., Marzec, M. L., Martin, C., & Binns, L. A. (2003). Identification and treatment of obstructive sleep apnea in adults and children with epilepsy: A prospective pilot study. Sleep Medicine, 4(6), 509–515.
Manni, R., & Terzaghi, M. (2010). Comorbidity between epilepsy and sleep disorders. Epilepsy Research, 90(3), 171–177.
Cognitive outcomes in epilepsy
Kong, Y., Zhao, K., Zeng, D., Lu, F., Li, X., Wu, Y., Jiang, Z., & Wen, W. (2024). Effects of vagus nerve stimulation on cognitive function in patients with epilepsy: A systematic review and meta-analysis. Frontiers in Neurology, 15, Article 1332882.
Cognitive enhancement and learning
Liu, F., & Li, Y. (2026). Sorting the mind: Cognitive enhancement through transcutaneous auricular vagus nerve stimulation: A systematic review and meta-analysis. Psychological Medicine, 56, Article e207.
Mild cognitive impairment
Wang, L., Zhang, J., Guo, C., He, J., Zhang, S., Wang, Y., Zhao, Y., Li, L., Wang, J., Hou, L., Li, S., Wang, Y., Hao, L., Zhao, Y., Wu, M., Fang, J., & Rong, P. (2022). The efficacy and safety of transcutaneous auricular vagus nerve stimulation in patients with mild cognitive impairment: A double blinded randomized clinical trial. Brain Stimulation, 15(6), 1405–1414.
Xu, T., Guo, C., Zhang, L., Cao, J., Li, M., Li, J., Li, K., Yang, J., & Fang, J. (2026). Rs-fMRI reveals that taVNS improves cognitive and emotional function in mild cognitive impairment by reconfiguration of “sensory relay-salience-default” cross-network effective connectivity: A randomized, double-blind, sham-controlled trial. Frontiers in Neurology, 17, Article 1891440.
Supplementary doctoral research
Leung, H. (2018). The physiological and psychological effects of electrical vagus nerve stimulation in patients with refractory epilepsy [Doctoral dissertation, University of Sheffield]. White Rose eTheses Online.
