Intermittent theta burst stimulation (iTBS) appears to be a potential intervention for enhancing motor recovery in post-stroke. However, the optimal parameters of iTBS protocol for lower limb dysfunction is ambiguous.
Objective
To evaluate the efficacy of iTBS in treating lower limb motor impairment after stroke and to explore the optimal stimulation parameters.
Methods
Relevant randomized controlled trials (RCTs) were retrieved from seven databases from their inception to May 2024. We defined primary outcomes as Fugl-Meyer Assessment for Lower Extremity (FMA-LE) and Berg Balance Scale (BBS). Subgroup analyses included stroke stage, stimulation sites, dosages and treatment sessions.
Results
The study results indicated that compared with the sham iTBS group, the iTBS group showed a significant improvement in lower limb motor recovery, balance, gait and activity of daily living (ADL). No significant effect was found in the Motor Evoked Potential amplitude. Subgroup analysis demonstrated that cerebellar iTBS had a therapeutic effect on subacute stroke patients. Furthermore, administrating 1200 pulses per session for a minimum of 15 sessions of iTBS intervention could significantly improve the balance and ADL performance.
Conclusion
iTBS could enhance lower limb motor function, improving the quality of life in subacute stroke patients with relatively high safety.
AderintoN.AbdulBasitM. O.OlatunjiG.AdejumoT. (2023). Exploring the transformative influence of neuroplasticity on stroke rehabilitation: A narrative review of current evidence. Annals of Medicine & Surgery, 85(9), 4425–4432. https://doi.org/10.1097/ms9.0000000000001137
2.
ArunK. M.SmithaK. A.SylajaP. N.KesavadasC. (2020). Identifying resting-state functional connectivity changes in the motor cortex using fNIRS during recovery from stroke. Brain TopogrBrain Topography, 33(6), 710–719. https://doi.org/10.1007/s10548-020-00785-2
3.
BaiZ.ZhangJ.FongK. N. K. (2022). Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: A systematic review and meta-analysis. Journal of NeuroEngineering and Rehabilitation, 19(1), 24. https://doi.org/10.1186/s12984-022-00999-4
4.
BoddingtonL. J.GrayJ. P.SchulzJ. M.ReynoldsJ. N. J. (2020). Low-intensity contralesional electrical theta burst stimulation modulates ipsilesional excitability and enhances stroke recovery. Experimental Neurology, 323, 113071. https://doi.org/10.1016/j.expneurol.2019.113071
5.
ChenJ.ShiM. F.ChenJ.ZhangJ.ChenR.TuJ. k.WuX. Q. (2023a). The effects of supplementing theta burst stimulation of the cerebellum with physical therapy on balance and gait recovery after a stroke: A randomized clinical trial. Chinese Journal of Physical Medicine and Rehabilitation, 45(5), 402–407. https://doi.org/10.3760/cma.j.issn.0254-1424.2023.05.004
6.
ChenY.SuW.GuiC. F.GuoQ. F.TanH. X.HeL.JiangH. H.WeiQ. C.GaoQ. (2023c). Effectiveness of cerebellar vermis intermittent theta-burst stimulation in improving trunk control and balance function for patients with subacute stroke: A randomised controlled trial protocol. BMJ Open, 13(1), e066356. https://doi.org/10.1136/bmjopen-2022-066356
7.
ChenS. Y.TsouM. H.ChenK. Y.LiuY. C.LinM. T. (2024). Impact of repetitive transcranial magnetic stimulation on cortical activity: A systematic review and meta-analysis utilizing functional near-infrared spectroscopy evaluation. Journal of NeuroEngineering and Rehabilitation, 21(1), 108. https://doi.org/10.1186/s12984-024-01407-9
8.
ChenS.ZhangS.YangW.ChenY.WangB.ChenJ.LiX.XieL.HuangH.ZengY.TianL.JiW.WeiX.LanY.LiH. (2023b). The effectiveness of intermittent theta burst stimulation for upper limb motor recovery after stroke: a systematic review and meta-analysis of randomized controlled trials. Frontiers in Neuroscience, 17. https://doi.org/10.3389/fnins.2023.1272003
9.
ChungS. W.HoyK. E.FitzgeraldP. B. (2015). Theta-burst stimulation: A new form of TMS treatment for depression?Depression and Anxiety, 32(3), 182–192. https://doi.org/10.1002/da.22335
10.
DengZ. D.LisanbyS. H.PeterchevA. V. (2013). Electric field depth-focality tradeoff in transcranial magnetic stimulation: Simulation comparison of 50 coil designs. Brain Stimulation, 6(1), 1–13. https://doi.org/10.1016/j.brs.2012.02.005
11.
DesforgesM.HadasI.MihovB.MorinY.Rochette BraünM.LioumisP.ZomorrodiR.ThéoretH.LepageM.DaskalakisZ. J.TremblayS. (2022). Dose-response of intermittent theta burst stimulation of the prefrontal cortex: A TMS-EEG study. Clinical Neurophysiology, 136, 158–172. https://doi.org/10.1016/j.clinph.2021.12.018
12.
DiamondD. M.DunwiddieT. V.RoseG. M. (1988). Characteristics of hippocampal primed burst potentiation in vitro and in the awake rat. The Journal of Neuroscience, 8(11), 4079–4088. https://doi.org/10.1523/jneurosci.08-11-04079.1988
13.
DingQ.ChenS.ChenJ.ZhangS.PengY.ChenY.ChenJ.LiX.ChenK.CaiG. (2022). Intermittent theta burst stimulation increases natural oscillatory frequency in ipsilesional motor cortex post-stroke: A transcranial magnetic stimulation and electroencephalography study. Frontiers in Aging Neuroscience, 14, 818340. https://doi.org/10.3389/fnagi.2022.818340
14.
DingQ.ZhangS.ChenS.ChenJ.LiX.ChenJ.PengY.ChenY.ChenK.CaiG.XuG.LanY. (2021). The effects of intermittent theta burst stimulation on functional brain network following stroke: An electroencephalography study. Frontiers in Neuroscience, 15, 755709. https://doi.org/10.3389/fnins.2021.755709
15.
Di PinoG.PellegrinoG.AssenzaG.CaponeF.FerreriF.FormicaD.RanieriF.TombiniM.ZiemannU.RothwellJ. C. (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
FeiginV. L.BraininM.NorrvingB.MartinsS.SaccoR. L.HackeW.FisherM.PandianJ.LindsayP. (2022). World Stroke Organization (WSO): Global stroke fact sheet 2022. International Journal of Stroke, 17(1), 18–29. https://doi.org/10.1177/17474930221080343
18.
GaoB.WangY.ZhangD.WangZ.WangZ. (2022). Intermittent theta-burst stimulation with physical exercise improves poststroke motor function: A systemic review and meta-analysis. Frontiers in Neurology, 13. https://doi.org/10.3389/fneur.2022.964627
19.
Grau-PellicerM.Chamarro-LusarA.Medina-CasanovasJ.Serdà FerrerB. C. (2019). Walking speed as a predictor of community mobility and quality of life after stroke. Topics in Stroke Rehabilitation, 26(5), 349–358. https://doi.org/10.1080/10749357.2019.1605751
20.
GuggisbergA. G.KochP. J.HummelF. C.BuetefischC. M. (2019). Brain networks and their relevance for stroke rehabilitation. Clinical Neurophysiology, 130(7), 1098–1124. https://doi.org/10.1016/j.clinph.2019.04.004
21.
HuangY. Z.EdwardsM. J.RounisE.BhatiaK. P.RothwellJ. C. (2005). Theta burst stimulation of the human motor cortex. Neuron, 45(2), 201–206. https://doi.org/10.1016/j.neuron.2004.12.033
JaeschkeR.SingerJ.GuyattG. H. (1989). Measurement of health status. Ascertaining the minimal clinically important difference. Controlled Clinical Trials, 10(4), 407–415. https://doi.org/10.1016/0197-2456(89)90005-6
24.
KochG.BonnìS.CasulaE. P.IosaM.PaolucciS.PellicciariM. C.CinneraA. M.PonzoV.MaiellaM.PicazioS.SallustioF.CaltagironeC. (2019). Effect of cerebellar stimulation on gait and balance recovery in patients with hemiparetic stroke: A randomized clinical trial. JAMA Neurol, 76(2), 170–178. https://doi.org/10.1001/jamaneurol.2018.3639
25.
KongQ.GuoZ. L.GaoC. F.LiuX. Q.YinC. J. (2024). Intermittent theta burst stimulation of the cerebellum can improve the walking of stroke survivors with lower limb dysfunction. Chinese Journal of Physical Medicine and Rehabilitation, 46(3), 226–231. https://doi.org/10.3760/cma.j.issn.0254-1424.2024.03.007
KuriakoseD.XiaoZ. (2020). Pathophysiology and treatment of stroke: Present status and future perspectives. International Journal of Molecular Sciences, 21(20), 7609. https://doi.org/10.3390/ijms21207609
28.
LiL.WangS. R. (2022). Effects of cerebellar theta-burst stimulation on lower extremity motor function in stroke patients. Chinese Journal of Rehabilitation Theory and Practice, 28(10), 1205–1210. https://doi.org/10.3969/j.issn.1006-9771.2022.10.011
29.
LiaoL. Y.XieY. J.ChenY.GaoQ. (2021). Cerebellar theta-burst stimulation combined with physiotherapy in subacute and chronic stroke patients: A pilot randomized controlled trial. Neurorehabilitation and Neural Repair, 35(1), 23–32. https://doi.org/10.1177/1545968320971735
30.
LiaoL. Y.ZhuY.PengQ. Y.GaoQ.LiuL.WangQ. H.GaoS. H.TaoY.HuangH.XuP. D.GaoC. Y. (2024). Intermittent theta-burst stimulation for stroke: Primary motor cortex versus cerebellar stimulation: A randomized sham-controlled trial. Stroke, 55(1), 156–165. https://doi.org/10.1161/STROKEAHA.123.044892
31.
LinL. F.ChangK. H.HuangY. Z.LaiC. H.LiouT. H.LinY. N. (2019). Simultaneous stimulation in bilateral leg motor areas with intermittent theta burst stimulation to improve functional performance after stroke: A feasibility pilot study. European Journal of Physical and Rehabilitation Medicine, 55(2), 162–168. https://doi.org/10.23736/S1973-9087.18.05245-0
32.
LinK. C.FuT.WuC. Y.WangY. H.LiuJ. S.HsiehC. J.LinS. F. (2010). Minimal detectable change and clinically important difference of the Stroke Impact Scale in stroke patients. Neurorehabilitation and Neural Repair, 24(5), 486–492. https://doi.org/10.1177/1545968309356295
33.
MantoM.BowerJ. M.ConfortoA. B.Delgado-GarcíaJ. M.da GuardaS. N.GerwigM.HabasC.HaguraN.IvryR. B.MariënP.MolinariM.NaitoE.NowakD. A.Oulad Ben TaibN.PelissonD.TescheC. D.TiliketeC.TimmannD. (2012). Consensus paper: Roles of the cerebellum in motor control–the diversity of ideas on cerebellar involvement in movement. The Cerebellum, 11(2), 457–487. https://doi.org/10.1007/s12311-011-0331-9
34.
Mateos-AparicioP.Rodríguez-MorenoA. (2019). The impact of studying brain plasticity. Frontiers in Cellular Neuroscience, 13, 66. https://doi.org/10.3389/fncel.2019.00066
35.
NathouC.DupreyE.SimonG.RazafimandimbyA.LerouxE.DollfusS.EtardO. (2018). Effects of low-and high-frequency repetitive transcranial magnetic stimulation on long-latency auditory evoked potentials. Neuroscience Letters, 686, 198–204. https://doi.org/10.1016/j.neulet.2018.09.002
36.
PetersD. M.FridrikssonJ.StewartJ. C.RichardsonJ. D.RordenC.BonilhaL.MiddletonA.GleichgerrchtE.FritzS. L. (2018). Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke. Human Brain Mapping, 39(1), 120–132. https://doi.org/10.1002/hbm.23829
37.
QiS.TianM.RaoY.SunC.LiX.QiaoJ.HuangZ. G. (2023). Applying transcranial magnetic stimulation to rehabilitation of poststroke lower extremity function and an improvement: Individual-target TMS. WIRES Cognitive Science, 14(2), e1636. https://doi.org/10.1002/wcs.1636
38.
RossiS.AntalA.BestmannS.BiksonM.BrewerC.BrockmollerJ.CarpenterL. L.CincottaM.ChenR.DaskalakisJ. D.Di LazzaroV.FoxM. D.GeorgeM. S.GilbertD.KimiskidisV. K.KochG.IlmoniemiR. J.LefaucheurJ. P.LeocaniL.LisanbyS. H.MiniussiC.PadbergF.Pascual-LeoneA.PaulusW.PeterchevA. V.QuartaroneA.RotenbergA.RothwellJ.RossiniP. M.SantarnecchiE.ShafiM. M.SiebnerH. R.UgawaY.WassermannE. M.ZangenA.ZiemannU.HallettM., & The basis of this article began with a Consensus Statement from the IFCN Workshop on "Present, Future of TMS: Safety, Ethical Guidelines", Siena, October 17-20, 2018, updating through April 2020 (2021). Safety and recommendations for TMS use in healthy subjects and patient populations, with updates on training, ethical and regulatory issues: Expert guidelines. Clinical Neurophysiology, 132(1), 269–306. https://doi.org/10.1016/j.clinph.2020.10.003
39.
SadeghihassanabadiF.FreyB. M.BackhausW.ChoeC. U.ZittelS.SchönG.BönstrupM.ChengB.ThomallaG.GerloffC.SchulzR. (2022). Structural cerebellar reserve positively influences outcome after severe stroke. Brain Communications, 4(6), fcac203. https://doi.org/10.1093/braincomms/fcac203
40.
SmithM. C.ByblowW. D.BarberP. A.StinearC. M. (2017). Proportional recovery from lower limb motor impairment after stroke. Stroke, 48(5), 1400–1403. https://doi.org/10.1161/strokeaha.116.016478
41.
SpitzN. A.PaceB. D.Ten EyckP.TrappN. T. (2022). Early improvement predicts clinical outcomes similarly in 10Hz rTMS and iTBS therapy for depression. Frontiers in Psychiatry, 13, 863225. https://doi.org/10.3389/fpsyt.2022.863225
TamuraS.MiyataK.KobayashiS.TakedaR.IwamotoH. (2022). The minimal clinically important difference in Berg Balance Scale scores among patients with early subacute stroke: A multicenter, retrospective, observational study. Topics in Stroke Rehabilitation, 29(6), 423–429. https://doi.org/10.1080/10749357.2021.1943800
44.
TanH. X.WeiQ. C.ChenY.XieY. J.GuoQ. F.HeL.GaoQ. (2021). The immediate effects of intermittent theta burst stimulation of the cerebellar vermis on cerebral cortical excitability during a balance task in healthy individuals: A pilot study. Frontiers in Human Neuroscience, 15, 748241. https://doi.org/10.3389/fnhum.2021.748241
45.
TangZ.HuangJ.ZhouY.RenJ.DuanX.FuX.PanR.WangR.ZhangP.DingM.SunJ.ZhangX.ChiQ.ZhangY.ZhangX.YuW.XuL.ZhangH.LiuH. (2024). Efficacy and safety of high-dose TBS on poststroke upper extremity motor impairment: A randomized controlled trial. Stroke, 55(9), 2212–2220. https://doi.org/10.1161/strokeaha.124.046597
46.
TangZ.LiuT.LiuY.HanK.SuW.ZhaoJ.ChiQ.ZhangX.ZhangH. (2023). Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: A study protocol for a randomized controlled trial. Frontiers in Neuroscience, 17, 1259872. https://doi.org/10.3389/fnins.2023.1259872
47.
UgawaY.UesakaY.TeraoY.HanajimaR.KanazawaI. (1995). Magnetic stimulation over the cerebellum in humans. Annals of Neurology, 37(6), 703–713. https://doi.org/10.1002/ana.410370603
48.
van DunK.BodranghienF.MantoM.MariënP. (2017). Targeting the cerebellum by noninvasive neurostimulation: A review. The Cerebellum, 16(3), 695–741. https://doi.org/10.1007/s12311-016-0840-7
49.
VeldemaJ.GharabaghiA. (2022). Non-invasive brain stimulation for improving gait, balance, and lower limbs motor function in stroke. Journal of NeuroEngineering and Rehabilitation, 19(1), 84. https://doi.org/10.1186/s12984-022-01062-y
50.
VolzL. J.HamadaM.MichelyJ.PoolE. M.NettekovenC.RothwellJ. C.Grefkes HermannC. (2019). Modulation of I-wave generating pathways by theta-burst stimulation: A model of plasticity induction. The Journal of Physiology, 597(24), 5963–5971. https://doi.org/10.1113/jp278636
51.
WangL.HuangG.ZhangL.YangJ.RenC.LiangC.ShenY.SuB. (2022). Effects of the intermittent theta burst stimulation of the cerebellar vermis on balance recovery after stroke: A study protocol for a randomized controlled trial. Frontiers in Aging Neuroscience, 14. https://doi.org/10.3389/fnagi.2022.881311
52.
XiaY.TangX.HuR.LiuJ.ZhangQ.TianS.WangW.LiC.ZhuY. (2022). Cerebellum-Cerebrum paired target magnetic stimulation on balance function and brain network of patients with stroke: A functional near-infrared spectroscopy pilot study. Frontiers in Neurology, 13, 1071328. https://doi.org/10.3389/fneur.2022.1071328
53.
XieY. J.WeiQ. C.ChenY.LiaoL. Y.LiB. J.TanH. X.JiangH. H.GuoQ. F.GaoQ. (2021). Cerebellar theta burst stimulation on walking function in stroke patients: A randomized clinical trial. Frontiers in Neuroscience, 15(9), Article 688569. https://doi.org/10.3389/fnins.2021.688569
54.
ZhangJ. J.BaiZ.FongK. N. (2022). Priming intermittent theta burst stimulation for hemiparetic upper limb after stroke: A randomized controlled trial. Stroke, 53(7), 2171–2181. https://doi.org/10.1161/STROKEAHA.121.037870
55.
ZhangJ. L., RH & LiuM. M. (2024). Effects of iTBS combined with sensorimotor integration training on neurophysiology in patients with post-stroke motor dysfunction. Chinese Journal of Convalescent Medicine, 33(3), 73–77. https://doi.org/10.13517/j.cnki.ccm.2024.03.016
56.
ZhuP. A.LiZ. L.LuQ. Q.NieY. Y.LiuH. W.KiernanE.YuanJ.ZhangL. J.BaoX. (2024). Can cerebellar theta-burst stimulation improve balance function and gait in stroke patients? A randomized controlled trial. European Journal of Physical and Rehabilitation Medicine, 60(3), 391–399. https://doi.org/10.23736/s1973-9087.24.08307-2
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
