Background and purpose. Within the concept of interhemispheric competition, technical modulation of the excitability of motor areas in the contralesional and ipsilesional hemisphere has been applied in an attempt to enhance recovery of hand function following stroke. This review critically summarizes the data supporting the use of novel electrophysiological concepts in the rehabilitation of hand function after stroke. Summary of review. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are powerful tools to inhibit or facilitate cortical excitability. Modulation of cortical excitability may instantaneously induce plastic changes within the cortical network of sensorimotor areas, thereby improving motor function of the affected hand after stroke. No significant adverse effects have been noted when applying brain stimulation in stroke patients. To date, however, the clinical effects are small to moderate and short lived. Future work should elucidate whether repetitive administration of rTMS or tDCS over several days and the combination of these techniques with behavioral training (ie, physiotherapy) could result in an enhanced effectiveness. Conclusion. Brain stimulation is a safe and promising tool to induce plastic changes in the cortical sensorimotor network to improve motor behavior after stroke. However, several methodological issues remain to be answered to further improve the effectiveness of these new approaches.
Kolominsky-Rabas PL, Weber M., Gefeller O., Neundörfer B., Heuschmann PUEpidemiology of ischemic stroke subtypes according to the TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study . Stroke. 2001;32:2735-2740.
2.
Lai SM, Studenski S., Duncan PW, Perera S.Persisting consequences of stroke measured by the Stroke Impact Scale . Stroke. 2002;33:1840-1844.
3.
Kwakkel G., Kollen BJ, Wagenaar RCLong-term effects of intensity of upper and lower limb training following stroke: a randomised trial. J Neurol Neurosurg Psychiatry . 2002;72:473-479.
4.
Nakayama H., Jorgensen HS, Raaschou HO, Olsen TSRecovery of upper extremity function in stroke subjects: the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1994;75:394-398.
5.
Hummel FC, Cohen LGNon-invasive brain stimulation: a new strategy to improve neurorehabilitation after stroke? Lancet Neurol. 2006;5:708-712.
6.
Khedr EM, Ahmed MA, Fathy N., Rothwell JCTherapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology. 2005 ;65:466-468.
7.
Takeuchi N., Chuma T., Matsuo Y., Watanabe I., Ikoma K.Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke. 2005;36:2681-2686.
8.
Mansur CG, Fregni F., Boggio PS, et al. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology. 2005;64:1802-1804.
9.
Kim YH, You SH, Ko MH, et al. Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke. 2006;37:1471-1476.
10.
Fregni F., Boggio PS, Valle AC, et al. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke. 2006;37:2115-2122.
11.
Talelli P., Greenwood RJ, Rothwell JCExploring theta burst stimulation as an intervention to improve motor recovery in chronic stroke. Clin Neurophysiol. 2007 ;118:333-342.
12.
Nowak DA, Grefkes C., Dafotakis M., Küst J., Karbe H., Fink GREffects of low frequency rTMS over contralesional motor cortex on movement kinematics and movement-related neural activation in subcortical stroke. Arch Neurol. 2008;65:741-747.
13.
Takeuchi N. , Tada T., Toshima M., Takayo C., Matsuo Y., Ikoma K.Inhibition of the unaffected motor cortex by 1 Hz repetitive transcranial magnetic stimulation enhances motor performance and training effect of the paretic hand in patients with chronic stroke. J Rehabil Med. 2008 ;40:298-303.
14.
Dafotakis M. , Grefkes C., Karbe H., Fink GR, Nowak DAEffects of rTMS on grip force control after subcortical stroke. Exp Neurol . 2008;211:407-412.
15.
Liepert J., Zittel S., Weiller C.Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial. Restor Neurol Neuosci . 2007;25:461-465.
16.
Hummel F., Cohen LGImprovement of motor function with noninvasive cortical stimulation in a patient with chronic stroke. Neurorehabil Neural Repair . 2005;19:14-19.
17.
Hummel F., Celnik P., Giraux P., et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain. 2005;128:490-499.
18.
Fregni F., Boggio PS, Mansur CG, et al. Transcranial direct current stimulation of the unaffected hemisphere in stroke patients. Neuroreport. 2005;16:1551-1555.
19.
Hummel FC, Voller B., Celnik P., et al. Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neurosci. 2006;7:73.
20.
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.
21.
Murase N., Duque J., Mazzocchio R., Cohen LGInfluence of interhemispheric interactions on motor function in chronic stroke . Ann Neurol. 2004;55:400-409.
22.
Kinsbourne M.Mechanisms of hemispheric interaction in man. In: Kinsbourne M, Smith WL , eds. Hemispheric Disconnection and Cerebral Function. Springfield, IL: Thomas; 1974:260-285.
23.
Bütefisch CM, Wessling M., Netz J., Seitz RJ, Hömberg V.Relationship between interhemispheric inhibition and motor cortex excitability in subacute stroke patients. Neurorehabil Neural Repair. 2008;22:4-21.
24.
Grefkes C., Eickhoff SB, Nowak DA, Dafotakis M., Fink GRDynamic intra-and interhemispheric interactions during unilateral and bilateral hand movements assessed with fMRI and DCM. Neuroimage. 2008;41:1382-1394.
25.
Nair DG, Hutchinson S., Fregni F., Alexander M., Pascual-Leone A., Schlaug G.Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients. Neuroimage. 2007;34:253-263.
26.
Gerloff C., Bushara K., Sailer A., et al. Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke . Brain. 2006;129:791-808.
27.
Ward NS, Brown MM, Thompson AJ, Frackowiak RSJ.Neural correlates of outcome after stroke: a cross-sectional fMRI study. Brain. 2003;126:1430-1448.
28.
Lotze M., Markert J., Sauseng P., Hoppe J., Plewnia C., Gerloff C.The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion. J Neurosci. 2006;26:6096-6102.
29.
Zhang W., Linden DJThe other side of the engram: experience-driven changes in neuronal intrinsic excitability. Nat Rev Neurosci. 2003;4:885-900.
30.
Maldonado MA , Allred RP, Felthauser EL, Jones TAMotor skills training, but not voluntary exercise, improves skilled reaching after unilateral ischemic lesions of the sensorimotor cortex in rats. Neurorehabil Neural Repair. 2008;22:250-261.
31.
Nudo RJ, Wise BM, SiFuentes F., Milliken GWNeural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996;272:1791-1794.
32.
Plautz EJ, Barbay S., Frost SB, et al. Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: a feasibility study in primates. Neurol Res. 2003;25:801-810.
33.
Hesse S., Werner C., Schonhardt EM, Bardeleben A., Jenrich W., Kirker SGCombined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: a pilot study. Restor Neurol Neurosci. 2007;25:9-15.
34.
Lee L., Siebner HR, Rowe JB, et al. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J Neurosci. 2003;23:5308-5318.
35.
Grefkes C., Nowak DA, Eickhoff SB, et al. Cortical connectivity after subcortical stroke assessed with functional magnetic resonance imaging. Ann Neurol. 2008;63:236-246.
36.
Brown JA, Lutsep HL, Weinand M., Cramer SCMotor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study. Neurosurgery. 2006 ;58:464-473.
37.
Levy R., Ruland S., Weinand M., Lowry D., Dafer R., Bakay R.Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: a multicenter feasibility study of safety and efficacy. J Neurosurg. 2008;108:707-714.
38.
Harvey RL, Winstein CJ; Everest Trial Group.Design for the Everest randomized trial of cortical stimulation and rehabilitation for arm function following stroke. Neurorehabil Neural Repair. 2009;23:32-44.
39.
Ameli M., Grefkes C., Wang L., et al. Differential effects of high-frequency rTMS on movement kinematics and neural activation in subcortical and cortical MCA stroke [abstract]. Neurology. 2008;70:A206.
40.
Schlaug G., Renga V., Nair D.Transcranial direct current stimulation in stroke recovery. Arch Neurol. 2008;65:1571-1576.
41.
Kobayashi M. , Hutchinson S., Théoret H., Schlaug G., Pascual-Leone A.Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements . Neurology. 2004;62:91-98.
42.
Dafotakis M. , Grefkes C., Wang L., Fink GR, Nowak DAThe effects of 1 Hz rTMS over the hand area of M1 improves movement kinematics of the ipsilateral hand. J Neural Transm. 2008;115:1269-1274.
43.
Kim YH, Park JW, Ko MH, Jang SH, Lee PKFacilitative effect of high frequency subthreshold repetitive transcranial magnetic stimulation on complex sequential motor learning in humans. Neurosci Lett. 2004;367:181-185.
44.
Conchou F., Loubinoux I., Castel-Lacanal E., et al. Neural substrates of low-frequency repetitive transcranial magnetic stimulation during movement in healthy subjects and acute stroke patients. A PET study [published online ahead of print December 15, 2008]. Hum Brain Mapp. doi: 10.1002/hbm.20690.
45.
Boggio PS, Alonso-Alonso M., Mansur CG, et al. Hand function improvement with low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere in a severe case of stroke . Am J Phys Med Rehabil.2006;85:927-930.
46.
Kirton A., Chen R., Friefeld S., Gunraj C., Pontigon AM, Deveber G.Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 2008;7:507-513.
47.
Yozbatiran N., Alonso-Alonso M., See J., et al. Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke. Stroke . 2009;40:309-312.
48.
Malcolm MP, Triggs WJ, Light KE, et al. Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial. Am J Phys Med Rehabil. 2007;86:707-715.
49.
Wolf SL, Winstein CJ, Miller JP, et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial . JAMA. 2006;296:2095-2104.
50.
Bestmann S. , Baudewig J., Siebner HR, Rothwell JC, Frahm J.Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits . Eur J Neurosci. 2004;19: 1950-1962.
51.
Anwander A. , Tittgemeyer M., von Cramon DY, Friederici AD, Knösche TRConnectivity-based parcellation of Broca’s area. Cereb Cortex. 2007;17:816-825.
52.
Fregni F., Pascual-Leone A.Technology insight: noninvasive brain stimulation in neurology-perspectives on the therapeutic potential of rTMS and tDCS. Nat Clin Pract Neurol. 2007;3:383-393.
53.
Talelli P., Rothwell J.Does brain stimulation after stroke have a future? Curr Opin Neurol. 2006;19:543-550.
54.
Siebner H., Rothwell JCTranscranial magnetic stimulation: new insights into representational cortical plasticity. Exp Brain Res. 2003;148:1-16.
55.
Poreisz C., Boros K., Antal A., Paulus W.Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res Bull. 2007 ;72:208-114.
56.
Wassermann EMRisk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Electroencephalogr Clin Neurophysiol. 1998;108:1-16.
