Vagus Nerve Stimulation in Stroke and Brain Injury Rehabilitation

Facilitating Recovery Through Neuromodulation and Neuroplasticity

Stroke, traumatic brain injury (TBI), and other structural brain injuries disrupt neural networks that support movement, language, cognition, emotional regulation, and autonomic function. Recovery depends not only on the extent of injury, but on the integrity of the systems that support regulation, adaptation, and learning. In practice, this means that structural damage alone does not determine outcome — the way the brain responds to that damage is equally important.

Vagus nerve stimulation (VNS) does not repair damaged tissue. Instead, it can modulate the biological conditions that support neuroplastic recovery, particularly when paired with targeted rehabilitation.

Recovery After Brain Injury Is a Learning Process

After stroke or brain injury, recovery relies on:

  • recruitment of alternative neural pathways
  • strengthening of surviving connections
  • reorganisation across distributed brain networks

This is what we call neuroplasticity. The process is experience-dependent. Improvements occur when the brain is repeatedly challenged in meaningful, task-specific ways. (See the helpful reference list at the end of this article.)

Rehabilitation therefore works by teaching the injured brain new solutions, not by restoring old circuits directly.

Why Neuroplasticity Is Central to Rehabilitation

Neuroplasticity refers to the brain’s ability to change its functional organisation in response to experience. After injury, plasticity allows:

  • intact regions to assume new roles
  • damaged functions to be partially re-expressed
  • inefficient early solutions to become more refined over time

However, neuroplasticity is not automatic or unlimited. It is gated by neuromodulatory systems that regulate attention, arousal, effort, and learning. These regulatory systems play a central role in determining whether injury leads to persistent dysfunction or to adaptive reorganisation. Two individuals with similar structural injuries may follow very different recovery trajectories depending on how effectively these systems support learning and adaptation.

Neuromodulation and the Role of the Brainstem

Key brainstem systems regulate whether experience leads to lasting change. Among these, the noradrenergic system, centred on the locus coeruleus, plays a critical role in:

  • learning rate
  • attentional gain
  • task engagement
  • consolidation of new skills.

These systems determine which experiences matter enough to reshape the brain.

BruceBlaus, CC BY-SA 4.0 , via Wikimedia Commons
VNS stimulates the locus coeruleus, the major source of noradrenaline (aka norepinephrine) in the brain.
Attribution: BruceBlaus, CC BY-SA 4.0 https://creativecommons.org/licenses/by-sa/4.0, via Wikimedia Commons

Beyond Neuroplasticity: VNS as an Immunomodulatory Therapy

Although vagus nerve stimulation is widely discussed in the context of neuroplasticity and rehabilitation, growing evidence suggests that its effects extend far beyond motor relearning alone. Increasingly, VNS is being investigated as a form of bioelectronic immunomodulation capable of influencing the inflammatory cascades that contribute to secondary injury after stroke.

Inflammation plays a central role in ischemic brain injury. Following stroke, activated microglia, infiltrating leukocytes, pro-inflammatory cytokines, oxidative stress, and blood–brain barrier disruption contribute to ongoing tissue damage well beyond the initial vascular event. Experimental studies suggest that VNS may help regulate these processes through activation of the cholinergic anti-inflammatory pathway (CAP), a vagally mediated neuroimmune mechanism in which acetylcholine signaling suppresses excessive inflammatory cytokine release.

Preclinical stroke models have demonstrated a range of potentially important effects associated with VNS, including reductions in infarct volume, suppression of pro-inflammatory cytokines such as TNF-α and IL-6, reduced oxidative stress, stabilization of blood–brain barrier integrity, promotion of anti-inflammatory M2 microglial polarization, and improvements in neurological outcome measures. These findings suggest that VNS may influence not only functional recovery after stroke, but also some of the biological processes that shape the extent of injury itself.

Importantly, this remains an evolving area of research. Much of the current evidence derives from animal models, and further clinical studies are needed to determine the degree to which these immunomodulatory effects translate into meaningful benefits in human stroke populations. Nevertheless, the convergence of evidence from neuroplasticity, autonomic regulation, inflammation research, and neuromodulation is increasingly positioning VNS as a potentially important adjunctive therapy within modern stroke rehabilitation and recovery frameworks.

How VNS Can Support Recovery After Stroke and Brain Injury

Afferent vagal pathways project to brainstem nuclei involved in neuromodulatory control, autonomic regulation, and inflammatory signalling. When applied conservatively, non-invasive transcutaneous auricular VNS can influence these systems, leading to changes in arousal, physiological stability, and neural responsiveness. These changes reflect modulation of the brain’s regulatory state, which in turn influences how effectively it can engage with and benefit from rehabilitation.

These effects can be beneficial in their own right, particularly in individuals with reduced alertness, fatigue, autonomic dysregulation, or impaired stress tolerance after brain injury.

When VNS is paired with task-specific rehabilitation, however, its effects are magnified and shaped toward functionally relevant outcomes. In this context, VNS does not replace therapy, but enhances the brain’s capacity to learn from it, increasing the brain’s responsiveness to rehabilitation. In practical terms, this means the same rehabilitation effort (physiotherapy, for example) may produce greater or more durable gains when paired with VNS.

Crucially:

  • VNS does not encode movement, language, or cognition
  • VNS does not replace therapy
  • VNS amplifies the effect of training and therapy
Molecular and microstructural changes associated with neuroplasticity.
Attribution: Gatto, RG. J. Integr. Neurosci. 2020, 19(3), 571–592. https://doi.org/10.31083/j.jin.2020.03.165

Evidence From Stroke Rehabilitation

The strongest evidence for VNS-enhanced recovery comes from post-stroke motor rehabilitation.

Clinical trials have shown that:

  • VNS paired with task-specific motor therapy leads to greater upper-limb recovery than therapy alone
  • benefits are seen even in the chronic phase of stroke
  • timing and pairing of stimulation with movement are critical

These findings demonstrate a clear proof of principle: neuromodulation can enhance rehabilitation-driven plasticity.

Beyond Motor Recovery

While much of the research has focused on motor outcomes, the same principles apply to other domains commonly affected by stroke and brain injury, including:

  • language and communication
  • attention and executive function
  • processing speed
  • emotional and behavioural regulation

Evidence strength varies across these domains, but the underlying mechanism — plasticity gated by neuromodulatory tone — is shared. The evidence base is expanding rapidly as more research is being done.

Traumatic Brain Injury and Diffuse Network Disruption

In TBI, injury often involves:

  • diffuse axonal damage
  • frontal and temporal network disruption
  • altered arousal and attentional control

This neuronal dysfunction can limit engagement with rehabilitation and slow learning. By modulating brainstem regulatory systems, VNS may help:

  • stabilise arousal
  • improve attentional readiness
  • support sustained engagement with therapy

As with stroke, benefits are greater when pairing stimulation with active rehabilitation, not just passive exposure.

Structural Injury, Timing, and Expectations

VNS is not restricted to the early phase of recovery. Neuroplastic change can occur:

  • months or years after injury
  • even when progress has plateaued

VNS is not expected to restore areas of established structural tissue loss (for example an infarct cavity), but it may support neuroplastic remodelling in surviving networks. In other conditions, volumetric MRI changes have been reported in association with VNS (e.g., hippocampal volume increases in treatment-resistant depression responders). This finding is preliminary and based on a small sample, but it certainly raises the intriguing possibility of improvements in brain structure in association with VNS.

We work on the assumption that VNS does not eliminate all deficits or bypass the need for effort and repetition. Recovery remains gradual, variable, and context-dependent.

How We Use VNS in Brain Injury Rehabilitation

At Ormond Neuroscience, VNS is integrated into a broader rehabilitation framework that may include:

Stimulation is applied conservatively, at sub-threshold intensities, and paired as closely as possible with training or therapy.

The goal is not to “force recovery,” but to create the conditions in which adaptive change is more likely.

Who May Benefit

VNS may be considered in individuals who:

  • in patients who have recently suffered a stroke, traumatic brain injury, or other brain injury
  • have residual deficits after stroke or brain injury
  • are engaging in rehabilitation but progressing slowly
  • have reached a plateau despite ongoing effort

Careful clinical assessment is essential to determine appropriateness.

In Summary

Recovery after stroke and brain injury depends on neuroplastic reorganisation driven by experience. Vagus nerve stimulation can modulate the regulatory systems that gate plasticity, enhancing the brain’s responsiveness to rehabilitation.

In this way, VNS is better understood not as a treatment for structural damage itself, but as a means of supporting the systems that determine how the brain adapts to that damage.

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

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:

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.

Selected References & Further Reading

Ay, I., Lu, J., Ay, H., & Sorensen, A. G. (2009). Vagus nerve stimulation reduces infarct size in rat focal cerebral ischemia. Neuroscience Letters, 459(3), 147–151.
Neuroscience Letters

Ay, I., Sorensen, A. G., & Ay, H. (2011). Vagus nerve stimulation reduces infarct size in rat focal cerebral ischemia: An unlikely role for cerebral blood flow. Brain Research, 1392, 110–115.
Brain Research

Ay, I., Napadow, V., & Ay, H. (2015). Electrical stimulation of the vagus nerve dermatome in the external ear is protective in rat cerebral ischemia. Brain Stimulation, 8(1), 7–12.
Brain Stimulation

Ay, I., Nasser, R., Simon, B., & Ay, H. (2016). Transcutaneous cervical vagus nerve stimulation ameliorates acute ischemic injury in rats. Brain Stimulation, 9(2), 166–173.
Brain Stimulation

Bao, S.-C., Khan, A., Song, R., & Tong, R. K.-Y. (2020). Rewiring the lesioned brain: Electrical stimulation for post-stroke motor restoration. Journal of Stroke, 22(1), 47–63.
Journal of Stroke

Capone, F., Miccinilli, S., Pellegrino, G., et al. (2017). Transcutaneous vagus nerve stimulation combined with robotic rehabilitation improves upper limb function after stroke. Neural Plasticity, 2017, 7876507.
Neural Plasticity

Cheng, K., Wang, Z., Bai, J., Xiong, J., Chen, J., & Ni, J. (2022). Research advances in the application of vagus nerve electrical stimulation in ischemic stroke. Frontiers in Neuroscience, 16, 1043446.
Frontiers in Neuroscience

Dawson, J., Liu, C. Y., Francisco, G. E., et al. (2021). Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): A randomised, blinded, pivotal, device trial. The Lancet, 397(10284), 1545–1553.
The Lancet

Engineer, N. D., Kimberley, T. J., Prudente, C. N., Dawson, J., Tarver, W. B., & Hays, S. A. (2019). Targeted vagus nerve stimulation for rehabilitation after stroke. Frontiers in Neuroscience, 13, 280.
Frontiers in Neuroscience

Fan, P., Wu, C., & Liu, B. (2025). Ischemic stroke treatment by vagus nerve stimulation: A comprehensive review of mechanisms, clinical efficacy, and future directions. Journal of Neurorestoratology, 13, 100209.
Journal of Neurorestoratology

Ganguly, K., Khanna, P., Morecraft, R. J., & Lin, D. J. (2022). Modulation of neural co-firing to enhance network transmission and improve motor function after stroke. Neuron, 110(15), 2363–2385.
Neuron

Hays, S. A. (2016). Enhancing rehabilitative therapies with vagus nerve stimulation. Neurotherapeutics, 13(2), 382–394.
Neurotherapeutics

Jelinek, M., Lipkova, J., & Duris, K. (2024). Vagus nerve stimulation as immunomodulatory therapy for stroke: A comprehensive review. Experimental Neurology, 372, 114628.
Experimental Neurology

Keute, M., & Gharabaghi, A. (2021). Brain state-dependent vagus nerve stimulation: Challenges and opportunities. Journal of Neural Engineering, 18(4), 041002.
Journal of Neural Engineering

Kimberley, T. J., Pierce, D., Prudente, C. N., et al. (2018). Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke. Stroke, 49(11), 2789–2792.
Stroke

Khodaparast, N., Kilgard, M. P., Casavant, R., Ruiz, A., Qureshi, I., Ganzer, P. D., Rennaker, R. L., & Hays, S. A. (2014). Vagus nerve stimulation during rehabilitative training improves forelimb recovery after chronic ischemic stroke in rats. Neurorehabilitation and Neural Repair, 28(7), 698–706.
Neurorehabilitation and Neural Repair

Ma, J., Zhang, L., He, G., & Tan, X. (2019). Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activates angiogenesis to improve neurological recovery after stroke. Frontiers in Neuroscience, 13, 280.
Frontiers in Neuroscience

Pruitt, D. T., Schmid, A. N., Kim, L. J., Abe, C. M., Trieu, J. L., Choua, C., Hays, S. A., & Kilgard, M. P. (2021). Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury. Journal of Neurotrauma, 38(7), 871–883.
Journal of Neurotrauma

Vannemreddy, P. S., Cummings, M., Bahrii, R. V., & Slavin, K. V. (2025). Vagus nerve stimulation in stroke management: Brief review of evolution and present applications paired with rehabilitation. Brain Sciences, 15(4), 346.
Brain Sciences

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