Restricted accessResearch articleFirst published online 2026-3
Patient-Tailored Transcranial Direct Current Stimulation Versus Sham for Upper-Extremity Rehabilitation in Subacute Stroke Patients: A Feasibility and Pilot Trial
Stroke is a leading cause of upper-extremity (UE) motor impairments worldwide. Transcranial direct current stimulation (TDCS) may enhance UE recovery, but response variability remains a challenge.
Objective
This randomized, double-blinded feasibility and pilot clinical trial evaluated effects of patient-tailored TDCS versus sham on UE recovery in subacute stroke.
Methods
Patients with subacute ischemic stroke and UE impairment were randomized to receive either anodal TDCS or sham stimulation, during UE rehabilitation 3 times weekly for 4 weeks. Electrode placement was patient-tailored and optimized using electric field modeling and targeted the ipsilesional primary motor hand area (M1-HAND). Primary outcome was Fugl-Meyer Assessment of UE (FMA-UE) score at end-of-intervention (EOT) and 12-weeks follow-up. Feasibility and exploratory clinical outcomes were also assessed.
Results
24 participants were randomized into real (n = 12, mean age 63 years) and sham TDCS (n = 12, mean age 68 years). FMA-UE improved at EOT in both groups, but improvement was significantly larger in the real TDCS group (mean difference 4.5 points, 95% confidence interval (CI) −5.34-14.31, P = .011). The differences diminished at 12-week follow-up. Median compliance was 95.8 and 100%, for real- and sham-TDCS groups, respectively, with no severe adverse events.
Conclusions
Patient-tailored anodal TDCS over the ipsilesional M1-HAND may boost recovery of UE impairment in subacute stroke versus sham TDCS. This trial identified a clinically feasible framework for optimizing protocols of patient-tailored TDCS for larger-scale stroke trials. Despite the complex trial setup, the favorable safety profile supports future large-scale studies with improved stratification by UE impairment.
KatanMLuftA.Global burden of stroke. Semin Neurol. 2018;38(2):208-211. doi:10.1055/S-0038-1649503
2.
van der VlietRSellesRWAndrinopoulouER, et al. Predicting upper limb motor impairment recovery after stroke: a mixture model. Ann Neurol. 2020;87(3):383-393. doi:10.1002/ANA.25679
3.
FeysHDe WeerdtWVerbekeG, et al. Early and repetitive stimulation of the arm can substantially improve the long-term outcome after stroke: a 5-year follow-up study of a randomized trial. Stroke. 2004;35(4):924-929. doi:10.1161/01.STR.0000121645.44752.F7
4.
de SousaDGHarveyLADorschSGlinskyJ V.Interventions involving repetitive practice improve strength after stroke: a systematic review. J Physiother. 2018;64(4):210-221. doi:10.1016/j.jphys.2018.08.004
5.
StinearC.Prediction of recovery of motor function after stroke. Lancet Neurol. 2010;9(12):1228-1232. doi:10.1016/S1474-4422(10)70247-7
6.
PuigJBlascoGDaunis-I-EstadellaJ, et al. Decreased corticospinal tract fractional anisotropy predicts long-term motor outcome after stroke. Stroke. 2013;44(7):2016-2018. doi:10.1161/STROKEAHA.111.000382
7.
Sánchez-KuhnAPérez-FernándezCCánovasRFloresPSánchez-SantedF.Transcranial direct current stimulation as a motor neurorehabilitation tool: an empirical review. Biomed Eng Online. 2017;16(Suppl 1):76. doi:10.1186/S12938-017-0361-8
8.
LiuAVöröslakosMKronbergG, et al. Immediate neurophysiological effects of transcranial electrical stimulation. Nat Commun. 2018;9(1):5092. doi:10.1038/S41467-018-07233-7
9.
NitscheMAPaulusW.Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000;527(Pt 3):633-639. doi:10.1111/J.1469-7793.2000.T01-1-00633.X
10.
RahmanAReatoDArlottiM, et al. Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects. J Physiol. 2013;591(10):2563-2578. doi:10.1113/JPHYSIOL.2012.247171
11.
StaggCJAntalANitscheMA.Physiology of transcranial direct current stimulation. J ECT. 2018;34(3):144-152. doi:10.1097/YCT.0000000000000510
12.
LefebvreSDricotLLalouxP, et al. Increased functional connectivity one week after motor learning and tDCS in stroke patients. Neuroscience. 2017;340:424-435. doi:10.1016/J.NEUROSCIENCE.2016.10.066
13.
ElsnerBKwakkelGKuglerJMehrholzJ.Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials. J Neuroeng Rehabil. 2017;14(1):95. doi:10.1186/S12984-017-0301-7
14.
WiethoffSHamadaMRothwellJC.Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul. 2014;7(3):468-475. doi:10.1016/j.brs.2014.02.003
15.
LiLMUeharaKHanakawaT.The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies. Front Cell Neurosci. 2015; 9(MAY):181. doi:10.3389/FNCEL.2015.00181/BIBTEX
16.
MinjoliSSaturninoGBBlicherJU, et al. The impact of large structural brain changes in chronic stroke patients on the electric field caused by transcranial brain stimulation. Neuroimage Clin. 2017;15:106-117. doi:10.1016/J.NICL.2017.04.014
17.
EdwardsJDDominguez-VargasAURossoC, et al. A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable. Int J Stroke. 2024;19(2):145-157. doi:10.1177/17474930231203982
18.
SaturninoGBSiebnerHRThielscherAMadsenKH.Accessibility of cortical regions to focal TES: dependence on spatial position, safety, and practical constraints. Neuroimage. 2019;203:116183. doi:10.1016/j.neuroimage.2019.116183
19.
ThielscherAOpitzAWindhoffM.Impact of the gyral geometry on the electric field induced by transcranial magnetic stimulation. Neuroimage. 2011;54(1):234-243. doi:10.1016/j.neuroimage.2010.07.061
20.
HordacreBMcCambridgeABRiddingMCBradnamL V.Can transcranial direct current stimulation enhance poststroke motor recovery? Development of a theoretical patient-tailored model. Neurology. 2021;97(4):170-180. doi:10.1212/WNL.0000000000012187
21.
KolmosMMadsenMJLiuML, et al. Patient-tailored transcranial direct current stimulation to improve stroke rehabilitation: study protocol of a randomized sham-controlled trial. Trials. 2023;24(1):216. doi:10.1186/S13063-023-07234-Y
22.
KolmosMHarboe OlsenMGluudC, et al. Patient-tailored transcranial direct current stimulation versus sham to improve stroke rehabilitation – an updated protocol and detailed statistical analysis plan for the randomised PRACTISE feasibility and pilot trial. Published online 2024. doi:10.5281/zenodo.14177380
23.
World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053
24.
SmithSMJenkinsonMWoolrichMW, et al. Advances in functional and structural MR image analysis and implementation as FSL. NeuroImage. 2004;23(Suppl 1):S208-S219. doi:10.1016/j.neuroimage.2004.07.051.
25.
JenkinsonMSmithS.A global optimisation method for robust affine registration of brain images. Med Image Anal. 2001;5(2):143-156. doi:10.1016/s1361-8415(01)00036-6
26.
CerriSGreveDNHoopesA, et al. An open-source tool for longitudinal whole-brain and white matter lesion segmentation. Neuroimage Clin. 2023;38:103354. doi:10.1016/j.nicl.2023.103354
27.
WasserthalJNeherPMaier-HeinKH.TractSeg – fast and accurate white matter tract segmentation. Neuroimage. 2018; 183:239-253. doi:10.1016/J.NEUROIMAGE.2018.07.070
28.
TournierJDSmithRRaffeltD, et al. MRtrix3: a fast, flexible and open software framework for medical image processing and visualisation. Neuroimage. 2019;202:116137. doi:10.1016/j.neuroimage.2019.116137
29.
SaturninoGBPuontiONielsenJDAntonenkoDMadsenKHThielscherA.SimNIBS 2.1: a comprehensive pipeline for individualized electric field modelling for transcranial brain stimulation. In: MakarovSHornerMNoetscherG, eds. Brain and Human Body Modeling: Computational Human Modeling at EMBC 2018. Springer; 2019:3–25. doi:10.1007/978-3-030-21293-3_1
30.
RichardsonJDattaADmochowskiJParraLCFridrikssonJ.Feasibility of using high-definition transcranial direct current stimulation (HD-tDCS) to enhance treatment outcomes in persons with aphasia. NeuroRehabilitation. 2015;36(1):115-126. doi:10.3233/NRE-141199
31.
AlamMTruongDQKhadkaNBiksonM.Spatial and polarity precision of concentric high-definition transcranial direct current stimulation (HD-tDCS). Phys Med Biol. 2016;61(12):4506-4521. doi:10.1088/0031-9155/61/12/4506
32.
HubbardIJParsonsMWNeilsonCCareyLM.Task-specific training: evidence for and translation to clinical practice. Occup Ther Int. 2009;16(3-4):175-189. doi:10.1002/oti.275
33.
LundquistCBMariboT.The Fugl–Meyer assessment of the upper extremity: reliability, responsiveness and validity of the Danish version. Disabil Rehabil. 2017;39(9):934-939. doi:10.3109/09638288.2016.1163422
34.
R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing; 2013.
35.
ElsnerBKuglerJPohlMMehrholzJ.Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke. Cochrane Database Syst Rev. 2020;11(11):CD009645. doi:10.1002/14651858.CD009645.PUB4
36.
PiresRBaltarASanchezMP, et al. Do higher transcranial direct current stimulation doses lead to greater gains in upper limb motor function in post-stroke patients?Int J Environ Res Public Health. 2023;20(2):1279. doi:10.3390/IJERPH20021279
37.
ChhatbarPYRamakrishnanVKautzSGeorgeMSAdamsRJFengW.Transcranial direct current stimulation post-stroke upper extremity motor recovery studies exhibit a dose-response relationship. Brain Stimul. 2016;9(1):16-26. doi:10.1016/j.brs.2015.09.002
38.
FritschBReisJMartinowichK, et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron. 2010;66(2):198-204. doi:10.1016/j.neuron.2010.03.035
39.
ChowAMDShinJWangHKellawanJMPereiraHM. Influence of transcranial direct current stimulation dosage and associated therapy on motor recovery post-stroke: a systematic review and meta-analysis. Front Aging Neurosci. 2022;14:821915. doi:10.3389/fnagi.2022.821915
40.
LangCEMacDonaldJRGnipC.Counting repetitions: an observational study of outpatient therapy for people with hemiparesis post-stroke. J Neurol Phys Ther. 2007;31(1):3-10. doi:10.1097/01.npt.0000260568.31746.34
41.
LanghornePCouparFPollockA.Motor recovery after stroke: a systematic review. Lancet Neurol. 2009;8(8):741-754. doi:10.1016/S1474-4422(09)70150-4
42.
NiemannFRiemannSHubertAK, et al. Electrode positioning errors reduce current dose for focal tDCS set-ups: evidence from individualized electric field mapping. Clin Neurophysiol. 2024;162:201-209. doi:10.1016/j.clinph.2024.03.031
43.
JoundiRAAdekanyeJLeungAA, et al. Health state utility values in people with stroke: a systematic review and meta-analysis. J Am Heart Assoc. 2022;11(13):e024296. doi:10.1161/JAHA.121.024296
44.
SinghRDSPandhiAAlexandrovAV. Post stroke depression. In: AmbrosiPBAhmadRAbdullahiAAgrawalA, eds. New Insight Into Cerebrovascular Diseases, chapter 15, IntechOpen; 2019.
45.
KwakkelGLanninNABorschmannK, et al. Standardized measurement of sensorimotor recovery in stroke trials: consensus-based core recommendations from the stroke recovery and rehabilitation roundtable. Int J Stroke. 2017; 12(5):451-461. doi:10.1177/1747493017711813/SUPPL_FILE/WSO711813_SUPPLEMENTARY_TABLES.PDF
46.
LiYFanJYangJHeCLiS.Effects of transcranial direct current stimulation on walking ability after stroke: a systematic review and meta-analysis. Restor Neurol Neurosci. 2018; 36(1):59-71. doi:10.3233/RNN-170770
47.
MansouriFMir-MoghtadaeiANiranjanV, et al. Development and validation of a 3D-printed neuronavigation headset for therapeutic brain stimulation. J Neural Eng. 2018;15(4): 46034. doi:10.1088/1741-2552/aacb96
48.
ThraneGSunnerhagenKSMurphyMA.Upper limb kinematics during the first year after stroke: the stroke arm longitudinal study at the University of Gothenburg (SALGOT). J Neuroeng Rehabil. 2020;17(1):76. doi:10.1186/s12984-020-00705-2
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.
