Facilitation of corticospinal excitability by virtual reality exercise following anodal transcranial direct current stimulation in healthy volunteers and subacute stroke subjects

Yeun Joon Kim, Jeonghun Ku, Sangwoo Cho, Hyun Jung Kim, Yun Kyung Cho, Teo Lim, Youn Joo Kang, Yeun Joon Kim, Jeonghun Ku, Sangwoo Cho, Hyun Jung Kim, Yun Kyung Cho, Teo Lim, Youn Joo Kang

Abstract

Background: There is growing evidence that the combination of non-invasive brain stimulation and motor skill training is an effective new treatment option in neurorehabilitation. We investigated the beneficial effects of the application of transcranial direct current stimulation (tDCS) combined with virtual reality (VR) motor training.

Methods: In total, 15 healthy, right-handed volunteers and 15 patients with stroke in the subacute stage participated. Four different conditions (A: active wrist exercise, B: VR wrist exercise, C: VR wrist exercise following anodal tDCS (1 mV, 20 min) on the left (healthy volunteer) or affected (stroke patient) primary motor cortex, and D: anodal tDCS without exercise) were provided in random order on separate days. We compared during and post-exercise corticospinal excitability under different conditions in healthy volunteers (A, B, C, D) and stroke patients (B, C, D) by measuring the changes in amplitudes of motor evoked potentials in the extensor carpi radialis muscle, elicited with single-pulse transcranial magnetic stimulation. For statistical analyses, a linear mixed model for a repeated-measures covariance pattern model with unstructured covariance within groups (healthy or stroke groups) was used.

Results: The VR wrist exercise (B) facilitated post-exercise corticospinal excitability more than the active wrist exercise (A) or anodal tDCS without exercise (D) in healthy volunteers. Moreover, the post-exercise corticospinal facilitation after tDCS and VR exercise (C) was greater and was sustained for 20 min after exercise versus the other conditions in healthy volunteers (A, B, D) and in subacute stroke patients (B, D).

Conclusions: The combined effect of VR motor training following tDCS was synergistic and short-term corticospinal facilitation was superior to the application of VR training, active motor training, or tDCS without exercise condition. These results support the concept of combining brain stimulation with VR motor training to promote recovery after a stroke.

Figures

Figure 1
Figure 1
Experimental set-up with a virtual reality exercise program (A) and transcranial direct current stimulation (B).
Figure 2
Figure 2
Time points of the application of TMS. A series of 12 TMS were applied repeatedly and we measured pre-, during- and post –exercise MEPs in each condition (A,B,C; thick arrow). In condition D, we measured pre- and post-tDCS MEPs without exercise. TMS, transcranial magnetic stimulation, MEPs, motor evoked potentials, VR, virtual reality, tDCS, transcranial direct current stimulation.
Figure 3
Figure 3
Facilitation of corticospinal excitability. The increase in MEP amplitude after VR wrist exercise following tDCS (A) was greater and sustained for 20 min after exercise compared with the three other conditions (B,C,D) in healthy volunteers and other two conditions (B,C) in stroke patients (***P < 0.001, **P < 0.01, *P < 0.05). P value from the post hoc analysis with Bonferroni correction. Error bars indicate standard errors of the mean (SEM). MEPs, motor evoked potentials, VR, virtual reality, tDCS, transcranial direct current stimulation.
Figure 4
Figure 4
Attention and fatigue scales between conditions. Level of attention and fatigue was presented by VAS, from 1: ‘no attention’ to 7: ‘highest level of attention’ and from 1: ‘no fatigue’ to 7: ‘highest level of fatigue’. Error bars indicate SEM. P values were from ANOVA and t-test (**P < 0.01, *P < 0.05). VR: virtual reality, tDCS: transcranial direct current stimulation, VAS: visual analog scale.

References

    1. Dobkin BH. Clinical practice. Rehabilitation after stroke. N Engl J Med. 2005;352:1677–1684. doi: 10.1056/NEJMcp043511.
    1. Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol. 2004;61:1844–1848. doi: 10.1001/archneur.61.12.1844.
    1. Simpson LA, Eng JJ. Functional recovery following stroke: capturing changes in upper-extremity function. Neurorehabil Neural Repair. 2013;27:240–250. doi: 10.1177/1545968312461719.
    1. Langhorne P, Bernhardt J, Kwakkel G. Stroke rehabilitation. Lancet. 2011;377:1693–1702. doi: 10.1016/S0140-6736(11)60325-5.
    1. Hesse S, Waldner A, Mehrholz J, Tomelleri C, Pohl M, Werner C. Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: an exploratory, randomized multicenter trial. Neurorehabil Neural Repair. 2011;25:838–846. doi: 10.1177/1545968311413906.
    1. Nair DG, Renga V, Lindenberg R, Zhu L, Schlaug G. Optimizing recovery potential through simultaneous occupational therapy and non-invasive brain-stimulation using tDCS. Restor Neurol Neurosci. 2011;29:411–420.
    1. Nudo RJ. Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury. J Rehabil Med. 2003;41:7–10. doi: 10.1080/16501960310010070.
    1. Krakauer JW. Motor learning: its relevance to stroke recovery and neurorehabilitation. Curr Opin Neurol. 2006;19:84–90. doi: 10.1097/.
    1. Lucca LF. Virtual reality and motor rehabilitation of the upper limb after stroke: a generation of progress? J Rehabil Med. 2009;41:1003–1100. doi: 10.2340/16501977-0405.
    1. Sveistrup H. Motor rehabilitation using virtual reality. J Neuroeng Rehabil. 2004;1:10. doi: 10.1186/1743-0003-1-10.
    1. Laver KE, George S, Thomas S, Deutsch JE, Crotty M: Virtual reality for stroke rehabilitation. Cochrane Database Syst Rev. 2011, CD008349-DOI: 10.1002/14651858.CD008349.pub2., 9
    1. Subramanian SK, Lourenco CB, Chilingaryan G, Sveistrup H, Levin MF. Arm motor recovery using a virtual reality intervention in chronic stroke: randomized control trial. Neurorehabil Neural Repair. 2013;27:13–23. doi: 10.1177/1545968312449695.
    1. Saposnik G, Robert T, Mamdani M, Cheung D, Thorpe KE, McIlroy B, Willems J, Hall J, Cohen LG, Bayley M. Effectiveness of Virtual Reality using Wii Gaming technology in STroke Rehabilitation (EVREST): a randomized clinical trial and proof of principle. Stroke. 2010;41:E473–E473. doi: 10.1161/STR.0b013e3181e6c862.
    1. Turolla A, Dam M, Ventura L, Tonin P, Agostini M, Zucconi C, Kiper P, Cagnin A, Piron L. Virtual reality for the rehabilitation of the upper limb motor function after stroke: a prospective controlled trial. J Neuroeng Rehabil. 2013;10:85. doi: 10.1186/1743-0003-10-85.
    1. Bagce HF, Saleh S, Adamovich SV, Krakauer JW, Tunik E. Corticospinal excitability is enhanced after visuomotor adaptation and depends on learning rather than performance or error. J Neurophysiol. 2013;109:1097–1106. doi: 10.1152/jn.00304.2012.
    1. Adamovich SV, Fluet GG, Tunik E, Merians AS. Sensorimotor training in virtual reality: a review. NeuroRehabilitation. 2009;25:29–44.
    1. Nitsche MA, Paulus W. 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.
    1. Nitsche MA, Schauenburg A, Lang N, Liebetanz D, Exner C, Paulus W, Tergau F. Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci. 2003;15:619–626. doi: 10.1162/089892903321662994.
    1. Stagg CJ, Jayaram G, Pastor D, Kincses ZT, Matthews PM, Johansen-Berg H. Polarity and timing-dependent effects of transcranial direct current stimulation in explicit motor learning. Neuropsychologia. 2011;49:800–804. doi: 10.1016/j.neuropsychologia.2011.02.009.
    1. Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, Cohen LG. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128:490–499. doi: 10.1093/brain/awh369.
    1. Lindenberg R, Renga V, Zhu LL, Nair D, Schlaug G. Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. Neurology. 2010;75:2176–2184. doi: 10.1212/WNL.0b013e318202013a.
    1. Boggio PS, Ferrucci R, Rigonatti SP, Covre P, Nitsche M, Pascual-Leone A, Fregni F. Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease. J Neurol Sci. 2006;249:31–38. doi: 10.1016/j.jns.2006.05.062.
    1. Kang EK, Baek MJ, Kim S, Paik NJ. Non-invasive cortical stimulation improves post-stroke attention decline. Restor Neurol Neurosci. 2009;27:645–650.
    1. Hallett M. Transcranial magnetic stimulation and the human brain. Nature. 2000;406:147–150. doi: 10.1038/35018000.
    1. Wassermann EM. Variation in the response to transcranial magnetic brain stimulation in the general population. Clin Neurophysiol. 2002;113:1165–1171. doi: 10.1016/S1388-2457(02)00144-X.
    1. Leonard G, Tremblay F. Corticomotor facilitation associated with observation, imagery and imitation of hand actions: a comparative study in young and old adults. Exp Brain Res. 2007;177:167–175. doi: 10.1007/s00221-006-0657-6.
    1. Cirillo J, Todd G, Semmler JG. Corticomotor excitability and plasticity following complex visuomotor training in young and old adults. Eur J Neurosci. 2011;34:1847–1856. doi: 10.1111/j.1460-9568.2011.07870.x.
    1. Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–198. doi: 10.1016/0022-3956(75)90026-6.
    1. Wilson B, Cockburn J, Halligan P. Development of a behavioral test of visuospatial neglect. Arch Phys Med Rehabil. 1987;68:98–102.
    1. van Marwijk HW, Wallace P, de Bock GH, Hermans J, Kaptein AA, Mulder JD. Evaluation of the feasibility, reliability and diagnostic value of shortened versions of the geriatric depression scale. Br J Gen Pract. 1995;45:195–199.
    1. Liebetanz D, Nitsche MA, Tergau F, Paulus W. Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain. 2002;125:2238–2247. doi: 10.1093/brain/awf238.
    1. Nitsche MA, Paulus W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology. 2001;57:1899–1901. doi: 10.1212/WNL.57.10.1899.
    1. Reis J, Schambra HM, Cohen LG, Buch ER, Fritsch B, Zarahn E, Celnik PA, Krakauer JW. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc Natl Acad Sci U S A. 2009;106:1590–1595. doi: 10.1073/pnas.0805413106.
    1. Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A, Fregni F. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor Neurol Neurosci. 2007;25:123–129.
    1. Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJ, Lima MC, Rigonatti SP, Marcolin MA, Freedman SD, Nitsche MA, Pascual-Leone A. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16:1551–1555. doi: 10.1097/01.wnr.0000177010.44602.5e.
    1. Fukumura K, Sugawara K, Tanabe S, Ushiba J, Tomita Y. Influence of mirror therapy on human motor cortex. Int J Neurosci. 2007;117:1039–1048. doi: 10.1080/00207450600936841.
    1. Perez MA, Lungholt BK, Nyborg K, Nielsen JB. Motor skill training induces changes in the excitability of the leg cortical area in healthy humans. Exp Brain Res. 2004;159:197–205. doi: 10.1007/s00221-004-1947-5.
    1. Paz R, Boraud T, Natan C, Bergman H, Vaadia E. Preparatory activity in motor cortex reflects learning of local visuomotor skills. Nat Neurosci. 2003;6:882–890. doi: 10.1038/nn1097.
    1. Blicher JU, Jakobsen J, Andersen G, Nielsen JF. Cortical excitability in chronic stroke and modulation by training: a TMS study. Neurorehabil Neural Repair. 2009;23:486–493. doi: 10.1177/1545968308328730.
    1. Ljubisavljevic M. Transcranial magnetic stimulation and the motor learning-associated cortical plasticity. Exp Brain Res. 2006;173:215–222. doi: 10.1007/s00221-006-0538-z.
    1. Hauptmann B, Skrotzki A, Hummelsheim H. Facilitation of motor evoked potentials after repetitive voluntary hand movements depends on the type of motor activity. Electroencephalogr Clin Neurophysiol. 1997;105:357–364. doi: 10.1016/S0924-980X(97)00031-3.
    1. Jensen JL, Marstrand PC, Nielsen JB. Motor skill training and strength training are associated with different plastic changes in the central nervous system. J Appl Physiol. 2005;99:1558–1568. doi: 10.1152/japplphysiol.01408.2004.
    1. Pascual-Leone A, Nguyet D, Cohen LG, Brasil-Neto JP, Cammarota A, Hallett M. Modulation of muscle responses evoked by transcranial magnetic stimulation during the acquisition of new fine motor skills. J Neurophysiol. 1995;74:1037–1045.
    1. Stinear CM, Barber PA, Coxon JP, Fleming MK, Byblow WD. Priming the motor system enhances the effects of upper limb therapy in chronic stroke. Brain. 2008;131:1381–1390. doi: 10.1093/brain/awn051.
    1. Liepert J, Miltner WH, Bauder H, Sommer M, Dettmers C, Taub E, Weiller C. Motor cortex plasticity during constraint-induced movement therapy in stroke patients. Neurosci Lett. 1998;250:5–8. doi: 10.1016/S0304-3940(98)00386-3.
    1. Subramanian SK, Levin MF. Viewing medium affects arm motor performance in 3D virtual environments. J Neuroeng Rehabil. 2011;8:36. doi: 10.1186/1743-0003-8-36.
    1. Piron L, Turolla A, Agostini M, Zucconi CS, Ventura L, Tonin P, Dam M. Motor learning principles for rehabilitation: a pilot randomized controlled study in poststroke patients. Neurorehabil Neural Repair. 2010;24:501–508. doi: 10.1177/1545968310362672.
    1. Kang YJ, Park HK, Kim HJ, Im SJ, Ku J, Cho S, Kim SI, Park ES. Upper extremity rehabilitation of stroke: facilitation of corticospinal excitability using virtual mirror paradigm. J Neuroeng Rehabil. 2012;9:71. doi: 10.1186/1743-0003-9-71.
    1. Liepert J, Classen J, Cohen LG, Hallett M. Task-dependent changes of intracortical inhibition. Exp Brain Res. 1998;118:421–426. doi: 10.1007/s002210050296.
    1. Chye L, Nosaka K, Murray L, Edwards D, Thickbroom G. Corticomotor excitability of wrist flexor and extensor muscles during active and passive movement. Hum Mov Sci. 2010;29:494–501. doi: 10.1016/j.humov.2010.03.003.
    1. Tinazzi M, Farina S, Tamburin S, Facchini S, Fiaschi A, Restivo D, Berardelli A. Task-dependent modulation of excitatory and inhibitory functions within the human primary motor cortex. Exp Brain Res. 2003;150:222–229.
    1. Kang YJ, Ku J, Park HK, Kim HJ. Facilitation of corticospinal excitability according to motor imagery and mirror therapy in healthy subjects and stroke patients. Ann Rehabil Med. 2011;35(6):747–758. doi: 10.5535/arm.2011.35.6.747.
    1. Harris-Love ML, Cohen LG. Noninvasive cortical stimulation in neurorehabilitation: a review. Arch Phys Med Rehabil. 2006;87:S84–S93. doi: 10.1016/j.apmr.2006.08.330.
    1. Ridding MC, Rothwell JC. Afferent input and cortical organisation: a study with magnetic stimulation. Exp Brain Res. 1999;126:536–544. doi: 10.1007/s002210050762.
    1. Ziemann U, Corwell B, Cohen LG. Modulation of plasticity in human motor cortex after forearm ischemic nerve block. J Neurosci. 1998;18:1115–1123.
    1. Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT. Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke. Restor Neurol Neurosci. 2009;27:199–207.
    1. Jacobs KM, Donoghue JP. Reshaping the cortical motor map by unmasking latent intracortical connections. Science. 1991;251:944–947. doi: 10.1126/science.2000496.
    1. Celnik P, Paik NJ, Vandermeeren Y, Dimyan M, Cohen LG. Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke. Stroke. 2009;40:1764–1771. doi: 10.1161/STROKEAHA.108.540500.
    1. Kim DY, Ohn SH, Yang EJ, Park CI, Jung KJ. Enhancing motor performance by anodal transcranial direct current stimulation in subacute stroke patients. Am J Phys Med Rehabil. 2009;88:829–836. doi: 10.1097/PHM.0b013e3181b811e3.
    1. Vines BW, Cerruti C, Schlaug G. Dual-hemisphere tDCS facilitates greater improvements for healthy subjects’ non-dominant hand compared to uni-hemisphere stimulation. BMC Neurosci. 2008;9:103. doi: 10.1186/1471-2202-9-103.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren