The impact of combined cerebellar transcranial alternating current stimulation and repetitive motor training on upper limb recovery in stroke patients

Authors

  • Basma Hussein Mohammed Lecturer of Physical Therapy for Neurology and Neurosurgery, Nahda University, Beniswif, Egypt
  • Reham Ali Mohamed Ali Ahmed Lecturer of Physical Therapy for Neuromuscular Disorders , Faculty of Physical Therapy, Beni-Suef University, New Beni-Suef, Egypt
  • Alyaa Abdallah Atallah Ahmed Zaid Lecturer of Physical Therapy Department of Physical Therapy for Internal Medicine and Geriatrics, Faculty of Physical Therapy, Horus University, New Damietta, Egypt
  • Azza Mohamed Atya Rehabilitation Sciences Department, Health and Rehabilitation Sciences College, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
  • Mostafa A. Abdelhameed Lecturer of Physical Therapy for surgery and burn, Faculty of Physical Therapy, Nahda University, Beniswif, Egypt

DOI:

https://doi.org/10.47197/retos.v72.117491

Keywords:

Cerebellar stimulation, neurorehabilitation, plasticity, repetitive motor training, stroke, tACS, upper limb

Abstract

Background: Upper limb motor impairment is a common and disabling consequence of stroke, often showing limited recovery with conventional rehabilitation. Non-invasive brain stimulation (NIBS), particularly transcranial alternating current stimulation (tACS), has emerged as a promising neuro-modulatory technique; however, the effects of cerebellar tACS remain underexplored.

Objective: To investigate the efficacy of cerebellar tACS combined with repetitive motor training (RMT) on upper limb motor recovery in patients with subacute ischemic stroke.

Methods: In this randomized, double-blind, sham-controlled trial, 52 patients with subacute ischemic stroke and unilateral upper limb hemiparesis were randomly assigned to receive either active cerebellar tACS or sham stimulation. Active tACS (70 Hz, 1 mA, 20 minutes) was delivered prior to daily RMT sessions (60 min/day, 5 days/week for 3 weeks). The primary outcome was upper limb motor function (Fugl-Meyer Assessment for Upper Extremity; FMA-UE). Secondary outcomes included manual dexterity (Box and Block Test; BBT), spasticity (Modified Ashworth Scale; MAS), and hand grip strength. Assessments were conducted at baseline, post-intervention, and 4-week follow-up by blinded evaluators.

Results: Participants receiving active tACS demonstrated significantly greater gains in FMA-UE (+11.2 vs. +3.8; p = 0.01), BBT (+7.1 vs. +1.8 blocks/min; p = 0.03), MAS (p = 0.04), and grip strength (+4.8 kg vs. +1.9 kg; p = 0.02) compared to the sham group. A large effect size was observed for FMA-UE (Cohen’s d > 0.8).

Conclusion: Cerebellar tACS combined with repetitive motor training significantly enhances upper limb motor recovery in subacute stroke. These findings support cerebellar neuromodulation as a promising adjunct in post-stroke rehabilitation.

References

Ambrus, G. G., Paulus, W., & Antal, A. (2012). Cutaneous perception thresholds of electrical stimulation methods: Comparison of tDCS and tRNS. Clinical Neurophysiology, 123(4), 829–835. https://doi.org/10.1016/j.clinph.2011.08.023

Antal, A., Alekseichuk, I., Bikson, M., Brockmöller, J., Brunoni, A. R., Chen, R., Cohen, L. G., Dowthwaite, G., Ellrich, J., Flöel, A., Fregni, F., George, M. S., Hamilton, R., Haueisen, J., Herrmann, C. S., Hummel, F. C., Lefaucheur, J. P., Liebetanz, D., Loo, C. K., … Paulus, W. (2017). Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clinical Neurophysiology, 128(9), 1774–1809.

Bastian, A. J. (2006). Learning to predict the future: The cerebellum adapts feedforward movement control. Current Opinion in Neurobiology, 16(6), 645–649. https://doi.org/10.1016/j.conb.2006.08.016Bhanpuri NH, Okamura AM, Bastian AJ. Predictive modeling by the cerebellum improves proprioception. J Neurosci. 2013;33(1):143–153.

Bohannon, R. W. (2008). Grip strength: An indispensable biomarker for older adults. Clinical Interven-tions in Aging, 3(4), 419–425. https://doi.org/10.2147/CIA.S24617

Bostan, A. C., & Strick, P. L. (2010). The cerebellum and basal ganglia are interconnected. Neuropsy-chology Review, 20(3), 261–270. https://doi.org/10.1007/s11065-010-9143-9

Brittain, J. S., Probert-Smith, P., Aziz, T. Z., & Brown, P. (2013). Tremor suppression by rhythmic tran-scranial current stimulation. Current Biology, 23(5), 436–440. https://doi.org/10.1016/j.cub.2013.01.068

Buckner, R. L. (2013). The cerebellum and cognitive function: 25 years of insight from anatomy and neuroimaging. Neuron, 80(3), 807–815. https://doi.org/10.1016/j.neuron.2013.10.044

Buckner, R. L., Krienen, F. M., Castellanos, A., Diaz, J. C., & Yeo, B. T. T. (2011). The organization of the human cerebellum estimated by intrinsic functional connectivity. Journal of Neurophysiology, 106(5), 2322–2345. https://doi.org/10.1152/jn.00339.2011

Daskalakis, Z. J., Paradiso, G. O., Christensen, B. K., Fitzgerald, P. B., Gunraj, C., & Chen, R. (2004). Ex-ploring the connectivity between the cerebellum and motor cortex in humans. Journal of Phys-iology, 557(2), 689–700. https://doi.org/10.1113/jphysiol.2003.059808

Ferrucci, R., Cortese, F., & Priori, A. (2015). Cerebellar tDCS: How to do it. Cerebellum, 14(1), 27–30. https://doi.org/10.1007/s12311-014-0617-3

Fertonani, A., & Miniussi, C. (2017). Transcranial electrical stimulation: What we know and do not know about mechanisms. The Neuroscientist, 23(2), 109–123. https://doi.org/10.1177/1073858416631966

Galea, J. M., Jayaram, G., Ajagbe, L., & Celnik, P. (2009). Modulation of cerebellar excitability by polari-ty-specific noninvasive direct current stimulation. Journal of Neuroscience, 29(28), 9115–9122. https://doi.org/10.1523/JNEUROSCI.2184-09.2009

Galea, J. M., Vazquez, A., Pasricha, N., de Xivry, J. J., & Celnik, P. (2011). Dissociating the roles of the cerebellum and motor cortex during adaptive learning: The motor cortex retains what the cer-ebellum learns. Cerebral Cortex, 21(8), 1761–1770. https://doi.org/10.1093/cercor/bhq246

Gong, Q., Yan, R., Chen, H., Li, L., Huang, X., & Zhou, Y. (2023). Effects of cerebellar transcranial direct current stimulation on rehabilitation of upper limb motor function after stroke. Frontiers in Neurology, 14, 1044333. https://doi.org/10.3389/fneur.2023.1044333

Grimaldi, G., Argyropoulos, G. P., Bastian, A., Cortes, M., Davis, N. J., Edwards, D. J., … Manto, M. (2016). Non-invasive cerebellar stimulation—A consensus paper. Cerebellum, 15(1), 95–110. https://doi.org/10.1007/s12311-015-0687-9

Hardwick, R. M., Forrence, A. D., Krakauer, J. W., Miall, R. C., & Celnik, P. A. (2019). Time-dependent competition between goal-directed and habitual response preparation in the human brain. Neuron, 103(3), 423–432.e5. https://doi.org/10.1016/j.neuron.2019.05.025

Hebb, D. O. (1949). The organization of behavior: A neuropsychological theory. Wiley.

Helfrich, R. F., Schneider, T. R., Rach, S., Trautmann-Lengsfeld, S. A., Engel, A. K., & Herrmann, C. S. (2014). Entrainment of brain oscillations by transcranial alternating current stimulation. Cur-rent Biology, 24(3), 333–339. https://doi.org/10.1016/j.cub.2013.12.041

Herrmann, C. S., Rach, S., Neuling, T., & Strüber, D. (2013). Transcranial alternating current stimula-tion: A review of the underlying mechanisms and modulation of cognitive processes. Frontiers in Human Neuroscience, 7, 279. https://doi.org/10.3389/fnhum.2013.00279

Iglesias, J. E., Insausti, R., Lerma-Usabiaga, G., Bocchetta, M., Van Leemput, K., Greve, D. N., … Caballe-ro-Gaudes, C. (2018). A probabilistic atlas of the human thalamic nuclei combining ex vivo MRI and histology. NeuroImage, 183, 314–326. https://doi.org/10.1016/j.neuroimage.2018.08.012

Ito, M. (2008). Control of mental activities by internal models in the cerebellum. Nature Reviews Neu-roscience, 9(4), 304–313. https://doi.org/10.1038/nrn2332

Ito, M. (2006). Cerebellar circuitry as a neuronal machine. Progress in Neurobiology, 78(3–5), 272–303. https://doi.org/10.1016/j.pneurobio.2006.02.006

Jayaram, G., Tang, B., Pallegadda, R., Vasudevan, E. V., Celnik, P., & Bastian, A. (2012). Modulating lo-comotor adaptation with cerebellar stimulation. Journal of Neurophysiology, 107(11), 2950–2957. https://doi.org/10.1152/jn.00645.2011

Koch, G., Bonnì, S., Casula, E. P., Iosa, M., Paolucci, S., Pellicciari, M. C., … Caltagirone, C. (2018). Role of the cerebellum in reward-based learning. Frontiers in Systems Neuroscience, 12, 68. https://doi.org/10.3389/fnsys.2018.00068

Koch, G., Mori, F., Marconi, B., Codeca, C., Pecchioli, C., Salerno, S., … Caltagirone, C. (2008). Changes in intracortical circuits of the human motor cortex following theta burst stimulation of the lateral cerebellum. Clinical Neurophysiology, 119(11), 2559–2569. https://doi.org/10.1016/j.clinph.2008.08.008

Kwah, L. K., Herbert, R. D., Harvey, L. A., & Diong, J. H. (2013). Half of the adults who recover from stroke still have reduced upper limb strength. Stroke Research and Treatment, 2013, 1–5. https://doi.org/10.1155/2013/428356

Langhorne, P., Bernhardt, J., & Kwakkel, G. (2009). Stroke rehabilitation. The Lancet, 373(9678), 1693–1702. https://doi.org/10.1016/S0140-6736(09)60892-4

Lefaucheur, J. P., Aleman, A., Baeken, C., Benninger, D. H., Brunelin, J., Di Lazzaro, V., … Ziemann, U. (2020). Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018). Clinical Neurophysiology, 131(2), 474–528. https://doi.org/10.1016/j.clinph.2019.11.002

Lefebvre, S., & Liew, S. L. (2017). Anatomical parameters of tDCS to modulate the motor system after stroke: A review. Frontiers in Neurology, 8, 29. https://doi.org/10.3389/fneur.2017.00029

Mathiowetz, V., Volland, G., Kashman, N., & Weber, K. (1985). Adult norms for the Box and Block Test of manual dexterity. American Journal of Occupational Therapy, 39(6), 386–391. https://doi.org/10.5014/ajot.39.6.386

Miall, R. C., & Reckess, G. Z. (2002). The cerebellum and the timing of coordinated movement. Experi-mental Brain Research, 147(3), 300–306. https://doi.org/10.1007/s00221-002-1269-8

Miniussi, C., & Rossini, P. M. (2011). Transcranial brain stimulation: Past, present, and future. Brain Stimulation, 4(4), 193–195. https://doi.org/10.1016/j.brs.2011.07.001

Mori, S., & Matsuyama, K. (1991). Predominant activation of ipsilateral descending pathways from the cerebellar fastigial nucleus in the cat. Journal of Neurophysiology, 66(6), 1881–1896. https://doi.org/10.1152/jn.1991.66.6.1881

Murphy, T. H., & Corbett, D. (2009). Plasticity during stroke recovery: From synapse to behaviour. Na-ture Reviews Neuroscience, 10(12), 861–872. https://doi.org/10.1038/nrn2735

Nakayama, H., Jørgensen, H. S., Raaschou, H. O., & Olsen, T. S. (1994). Compensation in recovery of upper extremity function after stroke: The Copenhagen Stroke Study. Archives of Physical Medicine and Rehabilitation, 75(8), 852–857. https://doi.org/10.1016/0003-9993(94)90108-2

Page, S. J., Fulk, G. D., & Boyne, P. (2012). Clinically important differences for the upper-extremity Fugl-Meyer Scale in people with minimal to moderate impairment due to chronic stroke. Phys-ical Therapy, 92(6), 791–798. https://doi.org/10.2522/ptj.20110009

Ptak, R., & Schnider, A. (2005). The dorsal attention network mediates orienting toward behaviorally relevant stimuli in spatial neglect. Journal of Cognitive Neuroscience, 17(4), 525–536. https://doi.org/10.1162/0898929053279520

Shadmehr, R., & Krakauer, J. W. (2008). A computational neuroanatomy for motor control. Experi-mental Brain Research, 185(3), 359–381. https://doi.org/10.1007/s00221-008-1280-5

Spencer, R. M., & Ivry, R. B. (2007). The temporal representation of in the cerebellum: Insights from motor timing. Cognitive Processing, 8(4), 219–225. https://doi.org/10.1007/s10339-007-0169-z

Takeuchi, N., & Izumi, S. (2013). Noninvasive brain stimulation for motor recovery after stroke: Mech-anisms and future views. Stroke Research and Treatment, 2013, 1–8. https://doi.org/10.1155/2013/923206

Veerbeek, J. M., van Wegen, E., van Peppen, R., van der Wees, P. J., Hendriks, E., Rietberg, M., & Kwakkel, G. (2014). What is the evidence for physical therapy poststroke? A systematic review and meta-analysis. PLoS One, 9(2), e87987. https://doi.org/10.1371/journal.pone.0087987

Vosskuhl, J., Strüber, D., & Herrmann, C. S. (2018). Non-invasive brain stimulation: A paradigm shift in understanding brain oscillations. Frontiers in Human Neuroscience, 12, 211. https://doi.org/10.3389/fnhum.2018.00211

Wischnewski, M., Schutter, D. J., & Nitsche, M. A. (2019). Effects of beta-tACS on corticospinal excitabil-ity: A meta-analysis. Brain Stimulation, 12(6), 1381–1389. https://doi.org/10.1016/j.brs.2019.07.023

Woytowicz, E. J., Rietschel, J. C., Goodman, R. N., Conroy, S. S., Sorkin, J. D., Whitall, J., & Wittenberg, G. F. (2017). Determining levels of upper extremity movement impairment by applying a cluster analysis to the Fugl-Meyer Assessment of the upper extremity. Archives of Physical Medicine and Rehabilitation, 98(3), 456–462. https://doi.org/10.1016/j.apmr.2016.06.023

Downloads

Published

02-10-2025

Issue

Section

Original Research Article

How to Cite

Mohammed, B. H., Ali Ahmed, R. A. M., Ahmed Zaid, A. A. A., Atya, A. M., & Abdelhameed, M. A. (2025). The impact of combined cerebellar transcranial alternating current stimulation and repetitive motor training on upper limb recovery in stroke patients. Retos, 72, 955-969. https://doi.org/10.47197/retos.v72.117491