Paired Vagus Nerve Stimulation for Stroke Bibliography
The following bibliography is a list of peer-reviewed publications related to Paired VNS™ Therapy for the treatment of chronic stroke and its mechanisms of action. This bibliography is not intended to be a comprehensive list of every publication on the subject and it does not include applications for Paired VNS that have been studied outside of stroke except where mechanism of action may overlap. Book chapters, abstracts, and posters are not included.
The Vivistim® Paired VNS™ System (Mobia Medical, Austin TX) is intended to be used to stimulate the vagus nerve during rehabilitation therapy in order to reduce upper extremity motor deficits and improve motor function in chronic ischemic stroke patients with moderate to severe arm impairment.
Clinical Studies and Systematic Reviews
- Patel, R., Spinelli-Guglielmo, L., Antares, K. A., Diedrich, A., & Zera, S. M. (2026). Vagus nerve stimulation paired with rehabilitation in the home environment for people with chronic post-stroke upper limb deficits: Preliminary findings. Advances in Rehabilitation Science and Practice, 15. https://doi.org/10.1177/27536351261447473
- Doherty, S. J., Prudente, C. N., Adham Hinds, R., Pierce, D., Engineer, N. D., Carrithers, J., Hansen, D., & Tarver, W. B. (2026). Study protocol for the Vivistim GRASP registry: capturing real-world outcomes of paired vagus nerve stimulation in the chronic stroke population. Frontiers in Stroke, 5,1751659.https://doi.org/10.3389/fstro.2026.1751659
- Patel, R., Spinelli-Guglielmo, L., Antares, K. A., Diedrich, A., & Zera, S. M. (2026). Vagus nerve stimulation paired with rehabilitation in the home environment for people with chronic post-stroke upper limb deficits: preliminary findings. Advances in Rehabilitation Science and Practice. Advance online publication. https://doi.org/10.1177/27536351261447473
- Saylor, A., Patrick, L., Reddy, C., & Gandhi, R. (2026). Vagus nerve stimulation paired with upper extremity rehabilitation for chronic stroke: real-world implementation and outcomes. Archives of Rehabilitation Research and Clinical Translation, 8(1), 100580. https://doi.org/10.1016/j.arrct.2025.100580
- Adelson, P. D., & Schmid, A. (2025). Safety of paired vagus nerve stimulation implantation in the presence of a cardiac pacemaker: a case report. Neurosurgery Practice, 6(4), e000180. https://doi.org/10.1227/neuprac.0000000000000180
- Doherty, S., Hinds, R. H. A., Engineer, N., & Prudente, C. N. (2025). Vagus nerve stimulation paired with rehabilitation in the home environment for people with chronic post-stroke upper limb deficits (VNS-REHAB At-Home): protocol for a feasibility trial. Advances in Rehabilitation Science and Practice, 14. https://doi.org/10.1177/27536351251406666
- Khan, I., Shakir, M., Vijayanarasimhan, V., Lodhi, B. A., Parker, J. J., Miller, K. J., Khan, M., Grewal, S. S., & Ali, R. (2025). Implantable vagus nerve stimulator-paired neurorehabilitation for upper limb function after ischemic stroke: evidence from a systematic review and meta-analysis with best practice recommendations. Neurosurgery, 97(6), 1242–1256. https://doi.org/10.1227/neu.0000000000003545
- Kimberley, T. J., Cramer, S. C., Wolf, S. L., Liu, C., Gochyyev, P., Dawson, J., & VNS-REHAB Trial Group. (2025). Long-term outcomes of vagus nerve stimulation paired with upper extremity rehabilitation after stroke. Stroke, 56(8), 2255–2265. https://doi.org/10.1161/STROKEAHA.124.050479
- Roy, J. M., Musmar, B., Ritz, C., Sizdahkhani, S., Karadimas, S., Papadopoulos, E., Patel, S., Wu, C., Jabbour, P., Rosenwasser, R. H., Tjoumakaris, S. I., & Gooch, M. R. (2025). Vagus nerve stimulation paired with rehabilitation for post-stroke recovery: a single center experience of patient satisfaction and outcomes. Clinical Neurology and Neurosurgery, 257, 109043. https://doi.org/10.1016/j.clineuro.2025.109043
- Beovich, A., Boose, J., Patel, R., & Wolf, S. L. (2024). Vagus nerve stimulation paired with rehabilitation for chronic stroke: characterizing responders. Journal of Neurologic Physical Therapy, 48(4), 217–223. https://doi.org/10.1097/NPT.0000000000000488
- Cummins, D. D., Kalagara, R., Downes, M. H., Park, H. J., Tosto-Mancuso, J., Putrino, D., Panov, F. E., & Kellner, C. P. (2024). Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case. Journal of Neurosurgery. Case Lessons, 7(11), CASE23676. https://doi.org/10.3171/CASE23676
- Lin, S., Rodriguez, C. O., & Wolf, S. L. (2024). Vagus nerve stimulation paired with upper extremity rehabilitation for chronic ischemic stroke: contribution of dosage parameters. Neurorehabilitation and Neural Repair, 38(8), 607–615.https://doi.org/10.1177/15459683241258769
- Schwarz, A., Feldman, M., Le, V., Dawson, J., Liu, C. Y., Francisco, G. E., Wolf, S. L., Dixit, A., Alexander, J., Ali, R., Brown, B. L., Feng, W., DeMark, L., Hochberg, L. R., Kautz, S. A., Majid, A., O’Dell, M. W., Redgrave, J., Turner, D. L., Kimberley, T. J., & Cramer, S. C. (2024). Association that neuroimaging and clinical measures have with change in arm impairment in a phase 3 stroke recovery trial. Annals of Neurology, 97(4), 709–719. https://doi.org/10.1002/ana.27156
- Vora, I., Gochyyev, P., Engineer, N., Wolf, S. L., & Kimberley, T. J. (2024). Distal versus proximal arm improvement after paired vagus nerve stimulation therapy after chronic stroke. Archives of Physical Medicine and Rehabilitation, 105(9), 1709–1717. https://doi.org/10.1016/j.apmr.2024.05.018
- Dawson, J., Engineer, N. D., Cramer, S. C., Wolf, S. L., Ali, R., O’Dell, M. W., Pierce, D., Prudente, C. N., Redgrave, J., Feng, W., Liu, C. Y., Francisco, G. E., Brown, B. L., Dixit, A., Alexander, J., DeMark, L., Krishna, V., Kautz, S. A., Majid, A., Tarver, B., Turner, D. L., & Kimberley, T. J. (2023). Vagus nerve stimulation paired with rehabilitation for upper limb motor impairment and function after chronic ischemic stroke: subgroup analysis of the randomized, blinded, pivotal, VNS-REHAB device trial. Neurorehabilitation and Neural Repair, 37(6), 367–373. https://doi.org/10.1177/15459683221129274
- Francisco, G. E., Engineer, N. D., Dawson, J., Kimberley, T. J., Cramer, S. C., Prudente, C. N., Pierce, D., Tarver, W. B., Hinds, R. H. A., Van de Winckel, A., & Yozbatiran, N. (2023). Vagus nerve stimulation paired with upper-limb rehabilitation after stroke: 2- and 3-year follow-up from the pilot study. Archives of Physical Medicine and Rehabilitation, 104(8), 1180–1187. https://doi.org/10.1016/j.apmr.2023.02.012
- Kimberley, T. J., Prudente, C. N., Engineer, N. D., Dickie, D. A., Bisson, T. A., & Van de Winckel, A. (2023). Vagus nerve stimulation paired with mobility training in chronic ischemic stroke: a case report. Physical Therapy, 103(12), pzad097. https://doi.org/10.1093/ptj/pzad097
- Liu, C. Y., Russin, J., Adelson, D. P., Jenkins, A., Hilmi, O., Brown, B., Lega, B., Whitworth, T., Bhattacharyya, D., Schwartz, T. H., Krishna, V., Williams, Z., Uff, C., Willie, J., Hoffman, C., Vandergrift, W. A., Achrol, A. S., Ali, R., Konrad, P., Edmonds, J., Kim, D., Bhatt, P., Tarver B. T., Pierce, D., Jain, R., Burress, C., Casavant, R., Prudente, C. N., & Engineer, N. D. (2022). Vagus nerve stimulation paired with rehabilitation for stroke: implantation experience from the VNS-REHAB trial. Journal of Clinical Neuroscience, 105, 122–128. https://doi.org/10.1016/j.jocn.2022.09.013
- Dawson, J., Liu, C. Y., Francisco, G. E., Cramer, S. C., Wolf, S. L., Dixit, A., Alexander, J., Ali, R., Brown, B. L., Feng, W., DeMark, L., Hochberg, L. R., Kautz, S. A., Majid, A., O’Dell, M. W., Pierce, D., Prudente, C. N., Redgrave, J., Turner, D. L., Engineer, N. D, & Kimberley, T. J. (2021). Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet, 397(10284), 1545–1553. https://doi.org/10.1016/S0140-6736(21)00475-X
- Dawson, J., Engineer, N. D., Prudente, C. N., Pierce, D., Francisco, G., Yozbatiran, N., Tarver, W. B., Casavant, R., Kline, D. K., Cramer, S. C., Van de Winckel, A., & Kimberley, T. J. (2020). Vagus nerve stimulation paired with upper-limb rehabilitation after stroke: one-year follow-up. Neurorehabilitation and Neural Repair, 34(7), 609–615. https://doi.org/10.1177/1545968320924361
- Dickie, D. A., Kimberley, T. J., Pierce, D., Engineer, N., Tarver, W. B., & Dawson, J. (2019). An exploratory study of predictors of response to vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Scientific Reports, 9(1), 15902. https://doi.org/10.1038/s41598-019-52092-x
- Kimberley, T. J., Prudente, C. N., Engineer, N. D., Pierce, D., Tarver, B., Cramer, S. C., Dickie, D. A., & Dawson, J. (2019). Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. European Stroke Journal, 4(4), 363–377. https://doi.org/10.1177/2396987319855306
- Kimberley, T. J., & Dawson, J. (2019). Response by Kimberley and Dawson regarding article, “Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke: a blinded randomized pilot study.” Stroke, 50(2), e38. https://doi.org/10.1161/STROKEAHA.118.024405
- Kumaria, A., & Tolias, C. M. (2019). Letter by Kumaria and Tolias regarding article, “Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke: a blinded randomized pilot study.” Stroke, 50(2), e37. https://doi.org/10.1161/STROKEAHA.118.024182
- Kilgard, M. P., Rennaker, R. L., Alexander, J., & Dawson, J. (2018). Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient. NeuroRehabilitation, 42(2), 159–165. https://doi.org/10.3233/NRE-172273
- Kimberley, T. J., Pierce, D., Prudente, C. N., Francisco, G. E., Yozbatiran, N., Smith, P., Tarver, B., Engineer, N. D., Alexander Dickie, D., Kline, D. K., Wigginton, J. G., Cramer, S. C., & Dawson, J. (2018). Vagus nerve stimulation paired with upper limb rehabilitation after chronic stroke. Stroke, 49(11), 2789–2792. https://doi.org/10.1161/STROKEAHA.118.022279
- Dawson, J., Pierce, D., Dixit, A., Kimberley, T. J., Robertson, M., Tarver, B., Hilmi, O., McLean, J., Forbes, K., Kilgard, M. P., Rennaker, R. L., Cramer, S. C., Walters, M., & Engineer, N. (2016). Safety, feasibility, and efficacy of vagus nerve stimulation paired with upper-limb rehabilitation after ischemic stroke. Stroke, 47(1), 143–150. https://doi.org/10.1161/STROKEAHA.115.010477
Reviews
- Bernhardt, A., Hahn, D., Jadav, N., Kelly, T. J., Camardo, K., Beltz, K., Berzins, D., & Serruya, M. D. (2025). Recent advances in vagus nerve stimulation for stroke rehabilitation. Current Physical Medicine and Rehabilitation Reports, 13(1), 41. https://doi.org/10.1007/s40141-025-00508-3
- Wang, L., Xu, Q., Luo, M., Xing, X., Wang, J., Liang, Y., Zhang, J., Sheng, R., Niu, S., & Wang, Y. (2025). Vagus nerve stimulation in various stages of stroke and associated functional impairments: a review. Neuroscience, 577, 80–113. https://doi.org/10.1016/j.neuroscience.2025.04.037
- Dawson, J., Abdul-Rahim, A. H., & Kimberley, T. J. (2024). Neurostimulation for treatment of post-stroke impairments. Nature Reviews Neurology, 20(5), 259–268. https://doi.org/10.1038/s41582-024-00953-z
- Malakouti, N., Serruya, M. D., Cramer, S. C., Kimberley, T. J., & Rosenwasser, R. H. (2024). Making sense of vagus nerve stimulation for stroke. Stroke, 55(2), 519–522. https://doi.org/10.1161/STROKEAHA.123.044576
- Schambra, H. M., & Hays, S. A. (2024). Vagus nerve stimulation for stroke rehabilitation: neural substrates, neuromodulatory effects and therapeutic implications. The Journal of Physiology, 603(3), 723–735. https://doi.org/10.1113/JP285566
- Dawson, J., & Abdul-Rahim, A. H. (2022). Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke. International Journal of Stroke, 17(10), 1061–1066. https://doi.org/10.1177/17474930221094684
- Morrison, R. A., Hays, S. A., & Kilgard, M. P. (2021). Vagus nerve stimulation as a potential adjuvant to rehabilitation for post-stroke motor speech disorders. Frontiers in Neuroscience, 15, 715928. https://doi.org/10.3389/fnins.2021.715928
- 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. https://doi.org/10.3389/fnins.2019.00280
- Hays, S. A. (2016). Enhancing rehabilitative therapies with vagus nerve stimulation. Neurotherapeutics, 13(2), 382–394. https://doi.org/10.1007/s13311-015-0417-z
Preclinical Studies and Mechanism of Action
- Addo, J. J. A., Neifert, C. L., Danaphongse, T. T. T., Abe, S. T., Ezhil, V., Kilgard, M. P., & Hays, S. A. (2025). Temporal parameters determine the efficacy of vagus nerve stimulation directed neural plasticity. Neurorehabilitation and Neural Repair, 39(11), 883–891. https://doi.org/10.1177/15459683251360725
- Bowles, S., Hickman, J., Peng, X., Williamson, W. R., Huang, R., Washington, K., Donegan, D., & Welle, C. G. (2022). Vagus nerve stimulation drives selective circuit modulation through cholinergic reinforcement. Neuron, 110(17), 2867–2885.e7. https://doi.org/10.1016/j.neuron.2022.06.017
- Morrison, R. A., Abe, S. T., Danaphongse, T., Ezhil, V., Somaney, A., Adcock, K. S., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2022). Common cholinergic, noradrenergic, and serotonergic drugs do not block VNS-mediated plasticity. Frontiers in Neuroscience, 16, 849291. https://doi.org/10.3389/fnins.2022.849291
- Rodenkirch, C., Carmel, J. B., & Wang, Q. (2022). Rapid effects of vagus nerve stimulation on sensory processing through activation of neuromodulatory systems. Frontiers in Neuroscience, 16, 922424. https://doi.org/10.3389/fnins.2022.922424
- Brougher, J., Sanchez, C. A., Aziz, U. S., Gove, K. F., & Thorn, C. A. (2021). Vagus nerve stimulation induced motor map plasticity does not require cortical dopamine. Frontiers in Neuroscience, 15, 693140. https://doi.org/10.3389/fnins.2021.693140
- Darrow, M. J., Mian, T. M., Torres, M., Haider, Z., Danaphongse, T., Seyedahmadi, A., Rennaker, R. L., Hays, S. A., & Kilgard, M. P. (2021). The tactile experience paired with vagus nerve stimulation determines the degree of sensory recovery after chronic nerve damage. Behavioural Brain Research, 396, 112910. https://doi.org/10.1016/j.bbr.2020.112910
- Kunii, N., Koizumi, T., Kawai, K., Shimada, S., & Saito, N. (2021). Vagus nerve stimulation amplifies task-induced cerebral blood flow increase. Frontiers in Human Neuroscience, 15, 726087. https://doi.org/10.3389/fnhum.2021.726087
- Morrison, R. A., Danaphongse, T. T., Abe, S. T., Stevens, M. E., Ezhil, V., Seyedahmadi, A., Adcock, K. S., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2021). High intensity VNS disrupts VNS-mediated plasticity in motor cortex. Brain Research, 1756, 147332. https://doi.org/10.1016/j.brainres.2021.147332
- Pruitt, D. T., Danaphongse, T. T., Lutchman, M., Patel, N., Reddy, P., Wang, V., Parashar, A., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2021). Optimizing dosing of vagus nerve stimulation for stroke recovery. Translational Stroke Research, 12(1), 65–71. https://doi.org/10.1007/s12975-020-00829-6
- Tseng, C.-T., Gaulding, S. J., Dancel, C. L. E., & Thorn, C. A. (2021). Local activation of α2 adrenergic receptors is required for vagus nerve stimulation induced motor cortical plasticity. Scientific Reports, 11(1), 21645. https://doi.org/10.1038/s41598-021-00976-2
- Darrow, M. J., Mian, T. M., Torres, M., Haider, Z., Danaphongse, T., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2020). Restoration of somatosensory function by pairing vagus nerve stimulation with tactile rehabilitation. Annals of Neurology, 87(2), 194–205. https://doi.org/10.1002/ana.25664
- Darrow, M. J., Torres, M., Sosa, M. J., Danaphongse, T. T., Haider, Z., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2020). Vagus nerve stimulation paired with rehabilitative training enhances motor recovery after bilateral spinal cord injury to cervical forelimb motor pools. Neurorehabilitation and Neural Repair, 34(3), 200–209. https://doi.org/10.1177/1545968319895480
- Morrison, R. A., Danaphongse, T. T., Pruitt, D. T., Adcock, K. S., Mathew, J. K., Abe, S. T., Abdulla, D. M., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2020). A limited range of vagus nerve stimulation intensities produce motor cortex reorganization when delivered during training. Behavioural Brain Research, 391, 112705. https://doi.org/10.1016/j.bbr.2020.112705
- Hulsey, D. R., Shedd, C. M., Sarker, S. F., Kilgard, M. P., & Hays, S. A. (2019). Norepinephrine and serotonin are required for vagus nerve stimulation directed cortical plasticity. Experimental Neurology, 320, 112975. https://doi.org/10.1016/j.expneurol.2019.112975
- Morrison, R. A., Hulsey, D. R., Adcock, K. S., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2019). Vagus nerve stimulation intensity influences motor cortex plasticity. Brain Stimulation, 12(2), 256–262. https://doi.org/10.1016/j.brs.2018.10.017
- Meyers, E. C., Solorzano, B. R., James, J., Ganzer, P. D., Lai, E. S., Rennaker, R. L., Kilgard, M. P., & Hays, S. A. (2018). Vagus nerve stimulation enhances stable plasticity and generalization of stroke recovery. Stroke, 49(3), 710–717. https://doi.org/10.1161/STROKEAHA.117.019202
- Hays, S. A., Ruiz, A., Bethea, T., Khodaparast, N., Carmel, J. B., Rennaker, R. L., & Kilgard, M. P. (2016). Vagus nerve stimulation during rehabilitative training enhances recovery of forelimb function after ischemic stroke in aged rats. Neurobiology of Aging, 43, 111–118. https://doi.org/10.1016/j.neurobiolaging.2016.03.030
- Hulsey, D. R., Hays, S. A., Khodaparast, N., Ruiz, A., Das, P., Rennaker, R. L., & Kilgard, M. P. (2016). Reorganization of motor cortex by vagus nerve stimulation requires cholinergic innervation. Brain Stimulation, 9(2), 174–181. https://doi.org/10.1016/j.brs.2015.12.007
- Khodaparast, N., Kilgard, M. P., Casavant, R., Ruiz, A., Qureshi, I., Ganzer, P. D., Rennaker, R. L., & Hays, S. A. (2016). Vagus nerve stimulation during rehabilitative training improves forelimb recovery after chronic ischemic stroke in rats. Neurorehabilitation and Neural Repair, 30(7), 676–684. https://doi.org/10.1177/1545968315616494
- Pruitt, D. T., Schmid, A. N., Kim, L. J., Abe, C. M., Trieu, J. L., Choua, C., Hays, S. A., Kilgard, M. P., & Rennaker, R. L. (2016). Vagus nerve stimulation delivered with motor training enhances recovery of function after traumatic brain injury. Journal of Neurotrauma, 33(9), 871–879. https://doi.org/10.1089/neu.2015.3972
- Hays, S. A., Khodaparast, N., Hulsey, D. R., Ruiz, A., Sloan, A. M., Rennaker, R. L., & Kilgard, M. P. (2014). Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke, 45(10), 3097–3100. https://doi.org/10.1161/STROKEAHA.114.006654
- Hays, S. A., Khodaparast, N., Ruiz, A., Sloan, A. M., Hulsey, D. R., Rennaker, R. L., & Kilgard, M. P. (2014). The timing and amount of vagus nerve stimulation during rehabilitative training affect poststroke recovery of forelimb strength. Neuroreport, 25(9), 676–682. https://doi.org/10.1097/WNR.0000000000000154
- Khodaparast, N., Hays, S. A., Sloan, A. M., Fayyaz, T., Hulsey, D. R., Rennaker, R. L., & Kilgard, M. P. (2014). Vagus nerve stimulation delivered during motor rehabilitation improves recovery in a rat model of stroke. Neurorehabilitation and Neural Repair, 28(7), 698–706. https://doi.org/10.1177/1545968314521006
- Hays, S. A., Rennaker, R. L., & Kilgard, M. P. (2013). Targeting plasticity with vagus nerve stimulation to treat neurological disease. Progress in Brain Research, 207, 275–299. https://doi.org/10.1016/B978-0-444-63327-9.00010-2
- Khodaparast, N., Hays, S. A., Sloan, A. M., Hulsey, D. R., Ruiz, A., Pantoja, M., Rennaker, R. L., & Kilgard, M. P. (2013). Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiology of Disease, 60, 80–88. https://doi.org/10.1016/j.nbd.2013.08.002
- Porter, B. A., Khodaparast, N., Fayyaz, T., Cheung, R. J., Ahmed, S. S., Vrana, W. A., Rennaker, R. L., & Kilgard, M. P. (2012). Repeatedly pairing vagus nerve stimulation with a movement reorganizes primary motor cortex. Cerebral Cortex, 22(10), 2365–2374. https://doi.org/10.1093/cercor/bhr316
- Engineer, N. D., Riley, J. R., Seale, J. D., Vrana, W. A., Shetake, J. A., Sudanagunta, S. P., Borland, M. S., & Kilgard, M. P. (2011). Reversing pathological neural activity using targeted plasticity. Nature, 470(7332), 101–104. https://doi.org/10.1038/nature09656
81-0007-0002 Rev. 5