Restricted accessResearch articleFirst published online 2025-11
Relationship Between Descending Neural Drives from the Non-Injured Hemisphere and Lower Limb Motor Function and Gait Ability in Patients Following Severe Stroke
The relationship between the functional recovery of patients in the subacute phase of stroke and descending neural drives from the non-injured hemisphere to the paretic lower limb muscles during movement remains unclear. We investigated this relationship in patients with severe paralysis.
Methods
Twenty-nine patients with stroke were recruited and categorized into three groups based on paralysis severity. Within 1 month of admission, each patient received 10 min of anodal tDCS applied to the cortical motor areas of the injured or non-injured hemispheres. Each stimulation condition was performed in a random order, one day at a time, with a 7-day washout period. Before and after each stimulation, patients performed multiple voluntary knee extensions on the paretic side 20% of their maximal strength, sustained for 6 s. Coherence analysis of EMG signals from proximal and distal segments of the vastus medialis muscle was conducted to quantify common neural drive from each cortical motor-related area based on coherence variations before and post stimulation in each condition. We investigated the relationship between the excitability of the descending neural pathway from the non-injured hemisphere in the initial phase and motor function recovery at 3 months.
Results
No significant differences emerged across groups in the change in coherence values when the non-injured hemisphere stimulated. However, within the severe group, an increase in β-band coherence following non-injured hemisphere stimulation correlated with greater recovery of paretic-side muscle strength and trunk function at 3 months.
Conclusion
Our findings deepen understanding of paralysis pathophysiology based on severity level and may support the development of targeted neuromodulation strategies to enhance motor recovery.
AuriatA. M.NevaJ. L.PetersS.FerrisJ. K.BoydL. A. (2015). A review of transcranial magnetic stimulation and multimodal neuroimaging to characterize post-stroke neuroplasticity. Frontiers in Neurology, 6(OCT). https://doi.org/10.3389/fneur.2015.00226
2.
Bani-AhmedA.CirsteaC. M. (2020). Ipsilateral primary motor cortex and behavioral compensation after stroke: A case series study. Experimental Brain Research, 238(2), 439–452. https://doi.org/10.1007/s00221-020-05728-8
3.
BarthélemyD.Willerslev-OlsenM.LundellH.ConwayB. A.KnudsenH.Biering-SørensenF.NielsenJ. B. (2010). Impaired transmission in the corticospinal tract and gait disability in spinal cord injured persons. Journal of Neurophysiology, 104(2), 1167–1176. https://doi.org/10.1152/jn.00382.2010
4.
BeneckeR.MeyerB.-U.FreundH.-J. (1991). Reorganisation of descending motor pathways in patients after hemispherectomy and severe hemispheric lesions demonstrated by magnetic brain stimulation. Experimental Brain Research, 83(2), 419–426. https://doi.org/10.1007/BF00231167
5.
BestmannS.KrakauerJ. W. (2015). The uses and interpretations of the motor-evoked potential for understanding behaviour. Experimental Brain Research, 233(3), 679–689. https://doi.org/10.1007/s00221-014-4183-7
6.
BigotJ.LongcampM.Dal MasoF.AmarantiniD. (2011). A new statistical test based on the wavelet cross-spectrum to detect time-frequency dependence between non-stationary signals: Application to the analysis of cortico-muscular interactions. NeuroImage, 55(4), 1504–1518. https://doi.org/10.1016/j.neuroimage.2011.01.033
7.
BiksonM.DattaA.ElwassifM. (2009). Establishing safety limits for transcranial direct current stimulation. Clinical Neurophysiology, 120(6), 1033–1034. https://doi.org/10.1016/j.clinph.2009.03.018
8.
BinderE.LeimbachM.PoolE. M.VolzL. J.EickhoffS. B.FinkG. R.GrefkesC. (2021). Cortical reorganization after motor stroke: A pilot study on differences between the upper and lower limbs. Human Brain Mapping, 42(4), 1013–1033. https://doi.org/10.1002/hbm.25275
9.
BowdenM. G.ClarkD. J.KautzS. A. (2010). Evaluation of abnormal synergy patterns poststroke: Relationship of the fugl-meyer assessment to hemiparetic locomotion. Neurorehabilitation and Neural Repair, 24(4), 328–337. https://doi.org/10.1177/1545968309343215
10.
ChangM. C.DoK. H.ChunM. H. (2015). Prediction of lower limb motor outcomes based on transcranial magnetic stimulation findings in patients with an infarct of the anterior cerebral artery. Somatosensory and Motor Research, 32(4), 249–253. https://doi.org/10.3109/08990220.2015.1091769
11.
ClelandB. T.MadhavanS. (2021). Ipsilateral motor pathways to the lower limb after stroke: Insights and opportunities. Journal of Neuroscience Research, 99(6), 1565–1578. https://doi.org/10.1002/jnr.24822
12.
DaSilvaA. F.VolzM. S.BiksonM.FregniF. (2011). Electrode positioning and montage in transcranial direct current stimulation. Journal of Visualized Experiments, 23(51), 2744. https://doi.org/10.3791/2744
13.
DuttaA.ChughS. (2012). Effect of transcranial direct current stimulation on cortico-muscular coherence and standing postural steadiness. EMBC 2011, 766–021.
14.
FisherK. M.ZaaimiB.WilliamsT. L.BakerS. N.BakerM. R. (2012). Beta-band intermuscular coherence: A novel biomarker of upper motor neuron dysfunction in motor neuron disease. Brain, 135(9), 2849–2864. https://doi.org/10.1093/brain/aws150
15.
FujiwaraT.SonodaS.OkajimaY.ChinoN. (2001). The relationships between trunk function and the findings of transcranial magnetic stimulation among patients with stroke. Journal of Rehabilitation Medicine, 33(6), 249–255. https://doi.org/10.1080/165019701753236428
16.
GregsonJ. M.LeathleyM. J.MooreA. P.SmithT. L.SharmaA. K.WatkinsC. L. (2000). Reliability of measurements of muscle tone and muscle power in stroke patients. Age and Ageing, 29(3), 223–228. https://doi.org/10.1093/ageing/29.3.223
17.
GrosseP.CassidyM. J.BrownP. (2002). EEG-EMG, MEG-EMG and EMG-EMG frequency analysis: Physiological principles and clinical applications. Clinical Neurophysiology, 113(10), 1523–1531. https://doi.org/10.1016/s1388-2457(02)00223-7
18.
HansenN. L.ConwayB. A.HallidayD. M.HansenS.PyndtH. S.Biering-SørensenF.NielsenJ. B. (2005). Reduction of common synaptic drive to ankle dorsiflexor motoneurons during walking in patients with spinal cord lesion. Journal of Neurophysiology, 94(2), 934–942. https://doi.org/10.1152/jn.00082.2005
19.
HayashiY.YamazakiK.KomatsuS.YamamotoN.UedaS.SatoK.YamaguchiT.HatoriK.HonagaK.TakakuraT.WadaF.TanumaA.FujiwaraT. (2024). Quadriceps muscle activity during walking with a knee ankle foot orthosis is associated with improved gait ability in acute hemiplegic stroke patients with severe gait disturbance. Frontiers in Neurology, 15. https://doi.org/10.3389/fneur.2024.1387607
20.
JangS. H.ChoM. K. (2022). Relationship of recovery of contralesional ankle weakness with the corticospinal and corticoreticular tracts in stroke patients. American Journal of Physical Medicine and Rehabilitation, 101(7), 659–665. https://doi.org/10.1097/PHM.0000000000001881
21.
JangS. H.YiJ. H.ChoiB. Y.ChangC. H.JungY. J.LeeH. D.YeoS. S. (2016). Changes of the corticospinal tract in the unaffected hemisphere in stroke patients: A diffusion tensor imaging study. Somatosensory and Motor Research, 33(1), 1–7. https://doi.org/10.3109/08990220.2016.1142435
22.
JayaramG.StaggC. J.EsserP.KischkaU.StinearJ.Johansen-BergH. (2012). Relationships between functional and structural corticospinal tract integrity and walking post stroke. Clinical Neurophysiology, 123(12), 2422–2428. https://doi.org/10.1016/j.clinph.2012.04.026
23.
KimY. H.YouS. H., KwonY. H.HallettM.KimJ. H.JangS. H. (2006). Longitudinal fMRI study for locomotor recovery in patients with stroke. Neurology, 67(2), 330–333. https://doi.org/10.1212/01.wnl.0000225178.85833.0d
24.
LiS.ChenY. T.FranciscoG. E.ZhouP.RymerW. Z. (2019). A unifying pathophysiological account for post-stroke spasticity and disordered motor control. Frontiers in Neurology, 10, 10–468. https://doi.org/10.3389/fneur.2019.00468
25.
LimaE.de Souza NetoJ. M. R.AndradeS. M. (2023). Effects of transcranial direct current stimulation on lower limb function, balance and quality of life after stroke: A systematic review and meta-analysis. Neurological Research, 45(9), 843–853. https://doi.org/10.1080/01616412.2023.2211457
26.
MadhavanS.RogersL. M.StinearJ. W. (2010). A paradox: After stroke, the non-lesioned lower limb motor cortex may be maladaptive. European Journal of Neuroscience, 32(6), 1032–1039. https://doi.org/10.1111/j.1460-9568.2010.07364.x
27.
McCambridgeA. B.StinearJ. W.ByblowW. D. (2018). Revisiting interhemispheric imbalance in chronic stroke: A tDCS study. Clinical Neurophysiology, 129(1), 42–50. https://doi.org/10.1016/j.clinph.2017.10.016
28.
MehrholzJ.WagnerK.RutteK.MeißnerD.PohlM. (2007). Predictive validity and responsiveness of the functional ambulation category in hemiparetic patients after stroke. Archives of Physical Medicine and Rehabilitation, 88(10), 1314–1319. https://doi.org/10.1016/j.apmr.2007.06.764
29.
NemanichS. T.LenchD. H.SutterE. N.KowalskiJ. L.FrancisS. M.MeekinsG. D.KrachL. E.FeymaT.GillickB. T. (2023). Safety and feasibility of transcranial direct current stimulation stratified by corticospinal organization in children with hemiparesis. European Journal of Paediatric Neurology, 43, 27–35. https://doi.org/10.1016/j.ejpn.2023.01.013
30.
NitscheM.PaulusW. (2000). Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. The Journal of Physiology, 527(3), 633–639. https://doi.org/10.1111/j.1469-7793.2000.t01-1-00633.x
31.
NitscheM. A.LiebetanzD.AntalA.LangN.TergauF.PaulusW. (2003). Chapter 27 modulation of cortical excitability by weak direct current stimulation - technical, safety and functional aspects. Supplements to Clinical Neurophysiology, 56(C), 255–276. https://doi.org/10.1016/S1567-424X(09)70230-2
32.
NojimaI.WatanabeT.SaitoK.TanabeS.KanazawaH. (2018). Modulation of EMG-EMG coherence in a choice stepping task. Frontiers in Human Neuroscience, 12, https://doi.org/10.3389/fnhum.2018.00050
33.
NortonJ. A.GorassiniM. A. (2006). Changes in cortically related intermuscular coherence accompanying improvements in locomotor skills in incomplete spinal cord injury. Journal of Neurophysiology, 95(4), 2580–2589. https://doi.org/10.1152/jn.01289.2005
34.
PlowE. B.SankarasubramanianV.CunninghamD. A.Potter-BakerK.VarnerinN.CohenL. G.SterrA.ConfortoA. B.MachadoA. G. (2016). Models to tailor brain stimulation therapies in stroke. Neural Plasticity, 2016, 1–17. https://doi.org/10.1155/2016/4071620
35.
PowerH. A.NortonJ. A.PorterC. L.DoyleZ.HuiI.ChanK. M. (2006). Transcranial direct current stimulation of the primary motor cortex affects cortical drive to human musculature as assessed by intermuscular coherence. Journal of Physiology, 577(3), 795–803. https://doi.org/10.1113/jphysiol.2006.116939
36.
Ritterband-RosenbaumA.HerskindA.LiX.Willerslev-OlsenM.OlsenM. D.FarmerS. F.NielsenJ. B. (2017). A critical period of corticomuscular and EMG–EMG coherence detection in healthy infants aged 9–25 weeks. Journal of Physiology, 595(8), 2699–2713. https://doi.org/10.1113/JP273090
37.
SchlaugG.RengaV.NairD. (2008). Transcranial direct current stimulation in stroke recovery. Archives of Neurology, 65(12), 1571–1576. https://doi.org/10.1001/archneur.65.12.1571
38.
StruttonP. H.BeithI. D.TheodorouS.CatleyM.McGregorA. H.DaveyN. J. (2004). Corticospinal activation of internal oblique muscles has a strong ipsilateral component and can be lateralised in man. Experimental Brain Research, 158(4), 474–479. https://doi.org/10.1007/s00221-004-1939-5
39.
TaninoG.SonodaS.WatanabeM.OkuyamaY.SasakiS.MuraiH.TomidaK.SuzukiA.KawakamiK.MiyasakaH.OrandA.TomitaY. (2014). Changes in the gait ability of hemiplegic patients with stroke in the subacute phase —A pattern based on their gait ability and degree of lower extremity motor paralysis on admission—. Japanese Journal of Comprehensive Rehabilitation Science, 5(0), 40–49. https://doi.org/10.11336/jjcrs.5.40
40.
ThairH.HollowayA. L.NewportR.SmithA. D. (2017). Transcranial direct current stimulation (tDCS): A beginner’s guide for design and implementation. Frontiers in Neuroscience, 11, 641. https://doi.org/10.3389/fnins.2017.00641
41.
TomczakC. R.GreidanusK. R.BoliekC. A. (2013). Modulation of chest wall intermuscular coherence: Effects of lung volume excursion and transcranial direct current stimulation. Journal of Neurophysiology, 110(3), 680–687. https://doi.org/10.1152/jn.00723.2012
42.
VeerbeekJ. M.WintersC.van WegenE. E. H.KwakkelG. (2018). Is the proportional recovery rule applicable to the lower limb after a first-ever ischemic stroke?PLoS ONE, 13(1). https://doi.org/10.1371/journal.pone.0189279
43.
VerheydenG.NieuwboerA.MertinJ.PregerR.KiekensC.De WeerdtW. (2004). The trunk impairment scale: A new tool to measure motor impairment of the trunk after stroke. Clinical Rehabilitation, 18(3), 326–334. https://doi.org/10.1191/0269215504cr733oa
44.
YangY. R.ChenI. H.LiaoK. K.HuangC. C.WangR. Y. (2010). Cortical reorganization induced by body weight-supported treadmill training in patients with hemiparesis of different stroke durations. Archives of Physical Medicine and Rehabilitation, 91(4), 513–518. https://doi.org/10.1016/j.apmr.2009.11.021
45.
YeoS. S.JangS. H.ParkG. Y.OhS. (2020). Effects of injuries to descending motor pathways on restoration of gait in patients with pontine hemorrhage. Journal of Stroke and Cerebrovascular Diseases, 29(7). https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.104857
46.
YooJ. S.ChoiB. Y.ChangC. H.JungY. J.KimS. H.JangS. H. (2014). Characteristics of injury of the corticospinal tract and corticoreticular pathway in hemiparetic patients with putaminal hemorrhage. BMC Neurology, 14(1). https://doi.org/10.1186/1471-2377-14-121
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