Repetitive Transcranial Magnetic Stimulation Combined with Mirror Therapy for Post-Stroke Upper Limb Motor Dysfunction: A Narrative Review of Recent Developments
DOI:
https://doi.org/10.54097/qfakkh15Keywords:
Repetitive Transcranial Magnetic Stimulation, Mirror Therapy, Stroke Survivors, Upper-limb Motor Impairment, Non-invasive Brain StimulationAbstract
More than half of stroke survivors have upper-limb motor impairment, and it is one of the main reasons for difficulties in daily life. Repeated Transcranial Magnetic Stimulation (rTMS) and Mirror Therapy (MT) are both non-invasive methods; however, they work differently by affecting cortical excitability and interhemispheric balance, respectively, and MT is achieved through visual feedback and the mirror neuron system to induce sensorimotor reorganization. It has not been found that the combined state is better than either separately. According to Hebbian plasticity and homeostatic metaplasia, this narrative review will explore how to design trials for and apply them in practice. Meta-analytic evidence is favorable. In a synthesis of 12 randomised trials (628 patients), combined non-invasive brain stimulation and MT improved upper limb function compared with either intervention alone (FMA-UE mean difference 5.97, 95% CI 5.01–6.93), and a smaller pooled effect on activity (SMD 0.82, 95% CI 0.61–1.02). Results of hand strength and dexterity also support combined therapy, but the FMA-UE outcome has not been consistently reproduced. Most trials are small, have different protocols, have a short follow-up period, and few are properly sham-controlled. These deficiencies lead to early-stage recommendations. We have set the following objectives: determine a suitable time and dose for rTMS; correlate treatment results with the integrity of the corticospinal tract and other biomarkers; conduct multi-centre sham-controlled trials of combined therapy; and investigate whether closed-loop stimulation can improve precision without increasing the volume of treatment.
Downloads
References
[1] Feigin, V. L., Stark, B. A., Johnson, C. O., et al. (2021). Global, regional, and national burden of stroke and its risk factors, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. The Lancet Neurology, 20(10), 795–820. https://doi.org/10.1016/S1474-4422(21)00252-0. DOI: https://doi.org/10.1016/S1474-4422(21)00252-0
[2] Langhorne, P., Coupar, F., & Pollock, A. (2009). Motor recovery after stroke: A systematic review. The Lancet Neurology, 8(8), 741–754. https://doi.org/10.1016/S1474-4422(09)70150-4. DOI: https://doi.org/10.1016/S1474-4422(09)70150-4
[3] Lim, K. B., Lee, H. J., Yoo, J., Yun, H. J., & Hwang, H. J. (2016). Efficacy of mirror therapy containing functional tasks in poststroke patients. Annals of Rehabilitation Medicine, 40(4), 629–636. https://doi.org/10.5535/arm.2016.40.4.629. DOI: https://doi.org/10.5535/arm.2016.40.4.629
[4] Pollock, A., Farmer, S. E., Brady, M. C., et al. (2014). Interventions for improving upper limb function after stroke. Cochrane Database of Systematic Reviews, (11), CD010820. https://doi.org/10.1002/14651858.CD010820.pub2. DOI: https://doi.org/10.1002/14651858.CD010820.pub2
[5] Lefaucheur, J. P., André-Obadia, N., Antal, A., et al. (2014). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology, 125(11), 2150–2206. https://doi.org/10.1016/j.clinph.2014.05.021. DOI: https://doi.org/10.1016/j.clinph.2014.05.021
[6] Long, H., Wang, H., Zhao, C., & Duan, Q. (2018). Effects of combining high- and low-frequency repetitive transcranial magnetic stimulation on upper limb hemiparesis in the early phase of stroke. Restorative Neurology and Neuroscience, 36(1), 21–30. https://doi.org/10.3233/RNN-170733. DOI: https://doi.org/10.3233/RNN-170733
[7] Deconinck, F. J. A., Smorenburg, A. R. P., Benham, A., Ledebt, A., Feltham, M. G., & Savelsbergh, G. J. P. (2015). Reflections on mirror therapy: A systematic review of the effect of mirror visual feedback on the brain. Neurorehabilitation and Neural Repair, 29(4), 349–361. https://doi.org/10.1177/1545968314546134. DOI: https://doi.org/10.1177/1545968314546134
[8] Gandhi, D. B. C., Sterba, A., Khatter, H., & Pandian, J. D. (2020). Mirror therapy in stroke rehabilitation: Current perspectives. Therapeutics and Clinical Risk Management, 16, 75–85. https://doi.org/10.2147/TCRM.S206883. DOI: https://doi.org/10.2147/TCRM.S206883
[9] Takeuchi, N., & Izumi, S. I. (2015). Combinations of stroke neurorehabilitation to facilitate motor recovery: Perspectives on Hebbian plasticity and homeostatic metaplasticity. Frontiers in Human Neuroscience, 9, 349. https://doi.org/10.3389/fnhum.2015.00349. DOI: https://doi.org/10.3389/fnhum.2015.00349
[10] Zhao, Q., Li, H., Liu, Y., et al. (2022). Non-invasive brain stimulation associated mirror therapy for upper-limb rehabilitation after stroke: Systematic review and meta-analysis of randomized clinical trials. Frontiers in Neurology, 13, 918956. https://doi.org/10.3389/fneur.2022.918956. DOI: https://doi.org/10.3389/fneur.2022.918956
[11] Abdelhaleem, N., Tawfek, A., Abouamra, H. S., et al. (2024). Combined effect of non-invasive brain stimulation with mirror therapy for improving motor function in patients with stroke: A systematic review with meta-analysis. Current Physical Medicine and Rehabilitation Reports, 12, 368–382. https://doi.org/10.1007/s40141-024-00448-4. DOI: https://doi.org/10.1007/s40141-024-00448-4
[12] Luo, Z., Zhou, Y., He, H., et al. (2020). Synergistic effect of combined mirror therapy on upper extremity in patients with stroke: A systematic review and meta-analysis. Frontiers in Neurology, 11, 155. https://doi.org/10.3389/fneur.2020.00155. DOI: https://doi.org/10.3389/fneur.2020.00155
[13] Cha, T. H., & Hwang, H. S. (2022). Rehabilitation interventions combined with noninvasive brain stimulation on upper limb motor function in stroke patients. Brain Sciences, 12(8), 994. https://doi.org/10.3390/brainsci12080994. DOI: https://doi.org/10.3390/brainsci12080994
[14] Fisicaro, F., Lanza, G., Grasso, A. A., et al. (2019). Repetitive transcranial magnetic stimulation in stroke rehabilitation: Review of the current evidence and pitfalls. Therapeutic Advances in Neurological Disorders, 12, 1756286419878317. https://doi.org/10.1177/1756286419878317. DOI: https://doi.org/10.1177/1756286419878317
[15] Du, J., Yang, F., Hu, J., et al. (2019). Effects of high- and low-frequency repetitive transcranial magnetic stimulation on motor recovery in early stroke patients: Evidence from a randomized controlled trial. NeuroImage: Clinical, 21, 101620. https://doi.org/10.1016/j.nicl.2018.10.013. DOI: https://doi.org/10.1016/j.nicl.2018.101620
[16] Safdar, A., Smith, M. C., Byblow, W. D., & Stinear, C. M. (2023). Applications of repetitive transcranial magnetic stimulation to improve upper limb motor performance after stroke: A systematic review. Neurorehabilitation and Neural Repair, 37(11–12), 812–827. https://doi.org/10.1177/15459683231209722. DOI: https://doi.org/10.1177/15459683231209722
[17] Yang, Y. W., Pan, W. X., & Xie, Q. (2020). Combined effect of repetitive transcranial magnetic stimulation and physical exercise on cortical plasticity. Neural Regeneration Research, 15(11), 1986–1994. https://doi.org/10.4103/1673-5374.282239. DOI: https://doi.org/10.4103/1673-5374.282239
[18] Yavuzer, G., Selles, R., Sezer, N., et al. (2008). Mirror therapy improves hand function in subacute stroke: A randomized controlled trial. Archives of Physical Medicine and Rehabilitation, 89(3), 393–398. https://doi.org/10.1016/j.apmr.2007.08.162. DOI: https://doi.org/10.1016/j.apmr.2007.08.162
[19] Tofani, M., Santecchia, L., Conte, A., & Berardi, A. (2022). Effects of mirror neurons-based rehabilitation techniques in hand injuries: A systematic review and meta-analysis. International Journal of Environmental Research and Public Health, 19(9), 5526. https://doi.org/10.3390/ijerph19095526. DOI: https://doi.org/10.3390/ijerph19095526
[20] Rossiter, H. E., Borrelli, M. R., Borchert, R. J., Bradbury, D., & Ward, N. S. (2015). Cortical mechanisms of mirror therapy after stroke. Neurorehabilitation and Neural Repair, 29(5), 444–452. https://doi.org/10.1177/1545968314554622. DOI: https://doi.org/10.1177/1545968314554622
[21] Zhang, J. J. Q., Fong, K. N. K., Welage, N., & Liu, K. P. Y. (2018). The activation of the mirror neuron system during action observation and action execution with mirror visual feedback in stroke: A systematic review. Neural Plasticity, 2018, 2321045. https://doi.org/10.1155/2018/2321045. DOI: https://doi.org/10.1155/2018/2321045
[22] Zhang, K., Ding, L., Wang, X., Zhuang, J., Tong, S., & Jia, J. (2024). Evidence of mirror therapy for recruitment of ipsilateral motor pathways in stroke recovery: A resting fMRI study. NeuroImage: Clinical, 41, 103574. https://doi.org/10.1016/j.nicl.2024.103574. DOI: https://doi.org/10.1016/j.neurot.2024.e00320
[23] Bai, Z., Fong, K. N. K., Zhang, J., & Hu, Z. (2020). Cortical mapping of mirror visual feedback training for unilateral upper extremity: A functional near-infrared spectroscopy study. Brain and Behavior, 10(1), e01489. https://doi.org/10.1002/brb3.1489. DOI: https://doi.org/10.1002/brb3.1489
[24] Arya, K. N. (2016). Underlying neural mechanisms of mirror therapy: Implications for motor rehabilitation in stroke. Neurology India, 64(1), 38–44. https://doi.org/10.4103/0028-3886.173622. DOI: https://doi.org/10.4103/0028-3886.173622
[25] Edwardson, M. A., Lucas, T. H., Carey, J. R., & Fetz, E. E. (2013). New modalities of brain stimulation for stroke rehabilitation. Experimental Brain Research, 224(3), 335–358. https://doi.org/10.1007/s00221-012-3315-1. DOI: https://doi.org/10.1007/s00221-012-3315-1
[26] Bienenstock, E. L., Cooper, L. N., & Munro, P. W. (1982). Theory for the development of neuron selectivity: Orientation specificity and binocular interaction in visual cortex. The Journal of Neuroscience, 2(1), 32–48. https://doi.org/10.1523/JNEUROSCI.02-01-00032.1982. DOI: https://doi.org/10.1523/JNEUROSCI.02-01-00032.1982
[27] Di Pino, G., Pellegrino, G., Assenza, G., et al. (2014). Modulation of brain plasticity in stroke: A novel model for neurorehabilitation. Nature Reviews Neurology, 10(10), 597–608. https://doi.org/10.1038/nrneurol.2014.162. DOI: https://doi.org/10.1038/nrneurol.2014.162
[28] Yan, W., Lin, Y., Chen, Y. F., & Wang, Y. (2025). Enhancing neuroplasticity for post-stroke motor recovery: Mechanisms, models, and neurotechnology. IEEE Transactions on Neural Systems and Rehabilitation Engineering, 33, 1367–1382. https://doi.org/10.1109/TNSRE.2025.3551147. DOI: https://doi.org/10.1109/TNSRE.2025.3551753
[29] Lin, X., Li, H., Chen, N., & Wu, X. (2025). Network meta-analysis of 4 rehabilitation methods with rTMS on upper limb function and daily activities in patients with stroke. Stroke, 56(5), 1208–1217. https://doi.org/10.1161/STROKEAHA.124.049546. DOI: https://doi.org/10.1161/STROKEAHA.124.049546
[30] Kim, J., & Yim, J. (2018). Effects of high-frequency repetitive transcranial magnetic stimulation combined with task-oriented mirror therapy training on hand rehabilitation of acute stroke patients. Medical Science Monitor, 24, 743–750. https://doi.org/10.12659/MSM.905636. DOI: https://doi.org/10.12659/MSM.905636
[31] Yang, J., Meng, D., Shao, Z., & Cheng, Q. (2018). High frequency transcranial magnetic stimulation combined with mirror therapy improves upper limb motor function post-stroke. Chinese Journal of Rehabilitation Medicine, 33(7), 775–781. (in Chinese).
[32] Chen, B., Jiang, L., Qiu, M., & Wang, C. (2023). Effects of 1 Hz repetitive transcranial magnetic stimulation combined with mirror therapy on upper limb motor function and neuroelectrophysiology in stroke patients with hemiplegia. Chinese Journal of Rehabilitation Medicine, 38(4), 498–504. (in Chinese)
[33] Ji, S. G., Cha, H. G., & Kim, M. K. (2014). Stroke recovery can be enhanced by using repetitive transcranial magnetic stimulation combined with mirror therapy. Journal of Magnetics, 19(1), 28–31. https://doi.org/10.4283/JMAG.2014.19.1.028. DOI: https://doi.org/10.4283/JMAG.2014.19.1.028
[34] Kim, W. S., Kwon, B. S., Seo, H. G., Park, J., & Paik, N. J. (2020). Low-frequency repetitive transcranial magnetic stimulation over contralesional motor cortex for motor recovery in subacute ischemic stroke: A randomized sham-controlled trial. Neurorehabilitation and Neural Repair, 34(9), 856–867. https://doi.org/10.1177/1545968320948610. DOI: https://doi.org/10.1177/1545968320948610
[35] Tang, Z., Han, K., Wang, R., Zhang, Y., & Zhang, H. (2022). Excitatory repetitive transcranial magnetic stimulation over the ipsilesional hemisphere for upper limb motor function after stroke: A systematic review and meta-analysis. Frontiers in Neurology, 13, 918597. https://doi.org/10.3389/fneur.2022.918597. DOI: https://doi.org/10.3389/fneur.2022.918597
[36] Lv, Y., Zhang, J. J., Wang, K., et al. (2023). Determining the optimal stimulation sessions for TMS-induced recovery of upper extremity motor function post stroke: A randomized controlled trial. Brain Sciences, 13(12), 1662. https://doi.org/10.3390/brainsci13121662. DOI: https://doi.org/10.3390/brainsci13121662
[37] Kim, W. S., & Paik, N. J. (2021). Safety review for clinical application of repetitive transcranial magnetic stimulation. Brain & Neurorehabilitation, 14(1), e6. https://doi.org/10.12786/bn.2021.14.e6. DOI: https://doi.org/10.12786/bn.2021.14.e6
[38] Hildesheim, F. E., Silver, A. N., Dominguez-Vargas, A. U., et al. (2022). Predicting individual treatment response to rTMS for motor recovery after stroke: A review and the CanStim perspective. Frontiers in Rehabilitation Sciences, 3, 795335. https://doi.org/10.3389/fresc.2022.795335. DOI: https://doi.org/10.3389/fresc.2022.795335
[39] Wang, L., Zhu, Q. X., Zhong, M. H., Zhou, R. Z., & Liu, X. Q. (2022). Effects of corticospinal tract integrity on upper limb motor function recovery in stroke patients treated with repetitive transcranial magnetic stimulation. Journal of Integrative Neuroscience, 21(2), 50. https://doi.org/10.31083/j.jin2102050. DOI: https://doi.org/10.31083/j.jin2102050
[40] Barreto, G., Fonseca, A., Albuquerque, R., & Santos, C. (2025). Predicting response to non-invasive brain stimulation in post-stroke upper extremity motor impairment: The importance of neurophysiological and clinical biomarkers. Neurological Sciences, 46, 2247–2259. https://doi.org/10.1007/s10072-025-08156-0. DOI: https://doi.org/10.1007/s10072-025-08156-0
[41] Zhang, L., Wang, C., Zhang, Z., & Sun, H. (2026). Effects of repetitive transcranial magnetic stimulation on upper limb motor recovery after stroke: An overview of systematic reviews. Frontiers in Neurology, 17, 1797218. https://doi.org/10.3389/fneur.2026.1797218. DOI: https://doi.org/10.3389/fneur.2026.1797218
[42] Barreto, G., Albuquerque, R., Santos, C., & Fonseca, A. (2026). PRESp-rTMS: A biomarker-based PREScription for personalized repetitive transcranial magnetic stimulation for stroke patients with upper extremity motor impairment. Topics in Stroke Rehabilitation. https://doi.org/10.1080/10749357.2025.2563224. DOI: https://doi.org/10.1080/10749357.2025.2563224
[43] Wei, D., Hua, X. Y., Zheng, M. X., Wu, J. J., & Xu, J. G. (2022). Robot-assisted virtual reality mirror therapy for upper limb motor dysfunction after stroke: Study protocol for a single-center randomized controlled clinical trial. BMC Neurology, 22, 307. https://doi.org/10.1186/s12883-022-02836-6. DOI: https://doi.org/10.1186/s12883-022-02836-6
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
