Understanding and enhancing motor recovery after stroke using transcranial magnetic stimulation.

Stroke is the leading cause of long-term disability. Understanding how people recover from stroke and other brain lesions remain one of the biggest conundrums in neuroscience. As a result, concerted efforts in recent years have focused on investigating the neurophysiological changes that occur in the brain after stroke, and in developing novel strategies to enhance motor recovery. In particular, transcranial magnetic stimulation (TMS) is a non-invasive tool that has been used to investigate the brain plasticity changes resulting from stroke and as a therapeutic modality to safely improve motor function. In this review, we discuss the contributions of TMS to understand how different motor areas, such as the ipsilesional hemisphere, secondary motor areas, and contralesional hemisphere are involved in motor recovery. We also consider recent studies using repetitive TMS (rTMS) in stroke patients to enhance upper extremity function. Although further studies are needed, these investigations provide an important starting point to understand the stimulation parameters and patient characteristics that may influence the optimal response to non-invasive brain stimulation. Future directions of rTMS are discussed in the context of post-stroke motor recovery.

[1]  Bruce T Volpe,et al.  Transcranial magnetic stimulation, synaptic plasticity and network oscillations , 2009, Journal of NeuroEngineering and Rehabilitation.

[2]  Babak Boroojerdi,et al.  Transcallosal inhibition in cortical and subcortical cerebral vascular lesions , 1996, Journal of the Neurological Sciences.

[3]  Chad D. Evans,et al.  Safety of 6-Hz Primed Low-Frequency rTMS in Stroke , 2008, Neurorehabilitation and neural repair.

[4]  B. Rosen,et al.  A functional MRI study of subjects recovered from hemiparetic stroke. , 1997, Stroke.

[5]  L. Cohen,et al.  Deficient intracortical inhibition (SICI) during movement preparation after chronic stroke , 2009, Neurology.

[6]  Tamara J. Dartnall,et al.  Corticomotor plasticity and learning of a ballistic thumb training task are diminished in older adults. , 2009, Journal of applied physiology.

[7]  B. Day,et al.  Interhemispheric inhibition of the human motor cortex. , 1992, The Journal of physiology.

[8]  R. Nudo,et al.  Effects of Repetitive Motor Training on Movement Representations in Adult Squirrel Monkeys: Role of Use versus Learning , 2000, Neurobiology of Learning and Memory.

[9]  J. Donoghue,et al.  Dynamic organization of primary motor cortex output to target muscles in adult rats I. Long-term patterns of reorganization following motor or mixed peripheral nerve lesions , 2004, Experimental Brain Research.

[10]  W. Fries,et al.  Motor recovery following capsular stroke. Role of descending pathways from multiple motor areas. , 1993, Brain : a journal of neurology.

[11]  Julie Duque,et al.  Intermanual Differences in Movement-related Interhemispheric Inhibition , 2007, Journal of Cognitive Neuroscience.

[12]  C. Braun,et al.  Motor learning elicited by voluntary drive. , 2003, Brain : a journal of neurology.

[13]  Á. Pascual-Leone,et al.  Safety and Behavioral Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation in Stroke , 2009, Stroke.

[14]  A. Gershon,et al.  Transcranial magnetic stimulation in the treatment of depression. , 2003, The American journal of psychiatry.

[15]  Sung Tae Kim,et al.  Long-term effects of rTMS on motor recovery in patients after subacute stroke. , 2010, Journal of rehabilitation medicine.

[16]  P. A. Tonali,et al.  Modulating cortical excitability in acute stroke: A repetitive TMS study , 2008, Clinical Neurophysiology.

[17]  Alvaro Pascual-Leone,et al.  6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke , 2010, Neuroscience Letters.

[18]  J. Rothwell,et al.  Informing Dose-Finding Studies of Repetitive Transcranial Magnetic Stimulation to Enhance Motor Function: A Qualitative Systematic Review , 2008, Neurorehabilitation and Neural Repair.

[19]  Rüdiger J. Seitz,et al.  Relationship Between Interhemispheric Inhibition and Motor Cortex Excitability in Subacute Stroke Patients , 2008, Neurorehabilitation and neural repair.

[20]  Leonid Kopylev,et al.  Age‐dependent changes in the ability to encode a novel elementary motor memory , 2003, Annals of neurology.

[21]  J. Nielsen,et al.  Cortical Excitability in Chronic Stroke and Modulation by Training: A TMS Study , 2009, Neurorehabilitation and neural repair.

[22]  J. Rothwell,et al.  Stages of Motor Output Reorganization after Hemispheric Stroke Suggested by Longitudinal Studies of Cortical Physiology , 2008, Cerebral cortex.

[23]  B. Bussel,et al.  Longitudinal Study of Motor Recovery After Stroke: Recruitment and Focusing of Brain Activation , 2002, Stroke.

[24]  L. Cohen,et al.  Increase in hand muscle strength of stroke patients after somatosensory stimulation , 2002, Annals of neurology.

[25]  Edward T. Bullmore,et al.  The relationship between motor deficit and hemisphere activation balance after stroke: A 3T fMRI study , 2007, NeuroImage.

[26]  M. Hommel,et al.  Vicarious function within the human primary motor cortex? A longitudinal fMRI stroke study. , 2005, Brain : a journal of neurology.

[27]  Richard D. Jones,et al.  Impairment and recovery of ipsilateral sensory-motor function following unilateral cerebral infarction. , 1989, Brain : a journal of neurology.

[28]  M. Hallett,et al.  Cortical motor representation of the ipsilateral hand and arm , 2004, Experimental Brain Research.

[29]  Sung Ho Jang,et al.  Facilitative effect of high frequency subthreshold repetitive transcranial magnetic stimulation on complex sequential motor learning in humans , 2004, Neuroscience Letters.

[30]  D. Buonomano,et al.  Cortical plasticity: from synapses to maps. , 1998, Annual review of neuroscience.

[31]  L. Cohen,et al.  Reorganization of the human ipsilesional premotor cortex after stroke. , 2004, Brain : a journal of neurology.

[32]  M. Knapp,et al.  Costs and disability among stroke patients. , 1999, Journal of public health medicine.

[33]  Gary W Thickbroom,et al.  Long-term changes in motor cortical organisation after recovery from subcortical stroke 1 1 Published on the World Wide Web on 1 December 2000. , 2001, Brain Research.

[34]  Fausto Viader,et al.  Spontaneous neurological recovery after stroke and the fate of the ischemic penumbra , 1996, Annals of neurology.

[35]  J. Liepert,et al.  Motor cortex disinhibition in acute stroke , 2000, Clinical Neurophysiology.

[36]  Hermann Ackermann,et al.  The role of the unaffected hemisphere in motor recovery after stroke , 2010, Human brain mapping.

[37]  L. Cohen,et al.  Enhancing encoding of a motor memory in the primary motor cortex by cortical stimulation. , 2004, Journal of neurophysiology.

[38]  M. Hallett,et al.  The role of the human motor cortex in the control of complex and simple finger movement sequences. , 1998, Brain : a journal of neurology.

[39]  Alvaro Pascual-Leone,et al.  Cumulative sessions of repetitive transcranial magnetic stimulation (rTMS) build up facilitation to subsequent TMS‐mediated behavioural disruptions , 2008, The European journal of neuroscience.

[40]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2009, Circulation.

[41]  Christian Grefkes,et al.  Differential effects of high‐frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke , 2009, Annals of neurology.

[42]  Volker Hömberg,et al.  Remote changes in cortical excitability after stroke. , 2003, Brain : a journal of neurology.

[43]  M. Cynader,et al.  Somatosensory cortical map changes following digit amputation in adult monkeys , 1984, The Journal of comparative neurology.

[44]  Alvaro Pascual-Leone,et al.  Brain Stimulation in Poststroke Rehabilitation , 2007, Cerebrovascular Diseases.

[45]  H. Siebner,et al.  Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex , 2004, Clinical Neurophysiology.

[46]  J. Baron,et al.  Motor imagery after stroke: Relating outcome to motor network connectivity , 2009, Annals of neurology.

[47]  B. Christensen,et al.  The mechanisms of interhemispheric inhibition in the human motor cortex , 2002, The Journal of physiology.

[48]  Michael C. Ridding,et al.  Reduced motor cortex plasticity following inhibitory rTMS in older adults , 2010, Clinical Neurophysiology.

[49]  J. Rothwell,et al.  Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke , 2005, Neurology.

[50]  F. Chollet,et al.  Neural substrates of low‐frequency repetitive transcranial magnetic stimulation during movement in healthy subjects and acute stroke patients. A PET study , 2009, Human brain mapping.

[51]  Sergio P. Rigonatti,et al.  A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients , 2005, Neurology.

[52]  P. Celnik,et al.  Reconnecting the dots after stroke , 2009, Annals of neurology.

[53]  S McEwen,et al.  Disablement following stroke. , 1999, Disability and rehabilitation.

[54]  C. Marsden,et al.  Corticocortical inhibition in human motor cortex. , 1993, The Journal of physiology.

[55]  F. Fregni,et al.  Can the 'yin and yang' BDNF hypothesis be used to predict the effects of rTMS treatment in neuropsychiatry? , 2008, Medical hypotheses.

[56]  W. Byblow,et al.  Combining Theta Burst Stimulation With Training After Subcortical Stroke , 2010, Stroke.

[57]  Gereon R. Fink,et al.  Interhemispheric Competition After Stroke: Brain Stimulation to Enhance Recovery of Function of the Affected Hand , 2009, Neurorehabilitation and neural repair.

[58]  L. Cohen,et al.  Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke. , 2007, Archives of physical medicine and rehabilitation.

[59]  G. Fink,et al.  Effects of rTMS on grip force control following subcortical stroke , 2008, Experimental Neurology.

[60]  M. Hallett,et al.  Depression of motor cortex excitability by low‐frequency transcranial magnetic stimulation , 1997, Neurology.

[61]  M. Hallett,et al.  Repetitive Transcranial Magnetic Stimulation–Induced Corticomotor Excitability and Associated Motor Skill Acquisition in Chronic Stroke , 2006, Stroke.

[62]  Markus Zahn,et al.  Transcranial magnetic stimulation and stroke: A computer-based human model study , 2006, NeuroImage.

[63]  D. Mozaffarian,et al.  Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. , 2009, Circulation.

[64]  Stéphane Lehéricy,et al.  Foot, face and hand representation in the human supplementary motor area , 2004, Neuroreport.

[65]  Yue Cao,et al.  Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. , 1998, Stroke.

[66]  J. Rothwell,et al.  Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex , 2000, Clinical Neurophysiology.

[67]  Sergio P. Rigonatti,et al.  Hand function improvement with low-frequency repetitive transcranial magnetic stimulation of the unaffected hemisphere in a severe case of stroke. , 2006, American journal of physical medicine & rehabilitation.

[68]  Alexander Münchau,et al.  Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans , 2003, NeuroImage.

[69]  G. Hagemann,et al.  Electrophysiological transcortical diaschisis after cortical photothrombosis in rat brain. , 1996, Stroke.

[70]  Steven D. Freedman,et al.  A Sham-Controlled Trial of a 5-Day Course of Repetitive Transcranial Magnetic Stimulation of the Unaffected Hemisphere in Stroke Patients , 2006, Stroke.

[71]  J. Liepert,et al.  Motor cortex disinhibition of the unaffected hemisphere after acute stroke , 2000, Muscle & nerve.

[72]  J. Liepert,et al.  Improvement of dexterity by single session low-frequency repetitive transcranial magnetic stimulation over the contralesional motor cortex in acute stroke: a double-blind placebo-controlled crossover trial. , 2007, Restorative neurology and neuroscience.

[73]  Á. Pascual-Leone,et al.  Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation , 2000, Clinical Neurophysiology.

[74]  John H. Martin,et al.  Motor Cortex Bilateral Motor Representation Depends on Subcortical and Interhemispheric Interactions , 2009, The Journal of Neuroscience.

[75]  鯨井 隆 Corticocortical inhibition in human motor cortex , 1994 .

[76]  Simon B. Eickhoff,et al.  Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling , 2010, NeuroImage.

[77]  Karl J. Friston,et al.  Functional reorganization of the brain in recovery from striatocapsular infarction in man , 1992, Annals of neurology.

[78]  L. Cohen,et al.  Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. , 2005, Brain : a journal of neurology.

[79]  R N Lemon,et al.  Contralateral and ipsilateral EMG responses to transcranial magnetic stimulation during recovery of arm and hand function after stroke. , 1996, Electroencephalography and clinical neurophysiology.

[80]  H. Mushiake,et al.  Reorganization of activity in the supplementary motor area associated with motor learning and functional recovery , 2004, Experimental Brain Research.

[81]  Richard S. J. Frackowiak,et al.  Motor system activation after subcortical stroke depends on corticospinal system integrity. , 2006, Brain : a journal of neurology.

[82]  Lumy Sawaki,et al.  Modulation of human corticomotor excitability by somatosensory input , 2002, The Journal of physiology.

[83]  Patrick Ragert,et al.  Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control , 2008, The Journal of physiology.

[84]  J. Tanji The supplementary motor area in the cerebral cortex , 1994, Neuroscience Research.

[85]  RP Dum,et al.  The origin of corticospinal projections from the premotor areas in the frontal lobe , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[86]  Julie Duque,et al.  Transcallosal inhibition in chronic subcortical stroke , 2005, NeuroImage.

[87]  J. Whitall,et al.  Bilateral arm training: why and who benefits? , 2008, NeuroRehabilitation.

[88]  R. A. Davidoff The pyramidal tract. , 1990, Neurology.

[89]  David W. McNeal,et al.  Selective long‐term reorganization of the corticospinal projection from the supplementary motor cortex following recovery from lateral motor cortex injury , 2010, The Journal of comparative neurology.

[90]  L. Cohen,et al.  Influence of interhemispheric interactions on motor function in chronic stroke , 2004, Annals of neurology.

[91]  R. Nudo,et al.  Neural Substrates for the Effects of Rehabilitative Training on Motor Recovery After Ischemic Infarct , 1996, Science.

[92]  J. C. Rothwell,et al.  Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke , 2007, Clinical Neurophysiology.

[93]  Tamer H. Emara,et al.  Repetitive transcranial magnetic stimulation at 1Hz and 5Hz produces sustained improvement in motor function and disability after ischaemic stroke , 2010, European journal of neurology.

[94]  Daniel Zeller,et al.  Theta-burst stimulation: Remote physiological and local behavioral after-effects , 2008, NeuroImage.

[95]  V. Pomeroy,et al.  Transcranial Magnetic Stimulation and Muscle Contraction to Enhance Stroke Recovery: A Randomized Proof-of-Principle and Feasibility Investigation , 2007, Neurorehabilitation and neural repair.

[96]  W. Kakuda,et al.  Low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy for poststroke patients with upper limb hemiparesis: preliminary study of a 15-day protocol , 2010, International journal of rehabilitation research. Internationale Zeitschrift fur Rehabilitationsforschung. Revue internationale de recherches de readaptation.

[97]  C. Darian‐Smith,et al.  Parallel pathways mediating manual dexterity in the macaque , 1999, Experimental Brain Research.

[98]  L. Cohen,et al.  Mechanisms underlying recovery of motor function after stroke. , 2004, Postgraduate medical journal.

[99]  J Valls-Solé,et al.  Rapid modulation of human cortical motor outputs following ischaemic nerve block. , 1993, Brain : a journal of neurology.

[100]  E. Khedr,et al.  Long‐term effect of repetitive transcranial magnetic stimulation on motor function recovery after acute ischemic stroke , 2010, Acta neurologica Scandinavica.

[101]  K. Ikoma,et al.  Repetitive transcranial magnetic stimulation over bilateral hemispheres enhances motor function and training effect of paretic hand in patients after stroke. , 2009, Journal of rehabilitation medicine.

[102]  P. Strick,et al.  Spinal Cord Terminations of the Medial Wall Motor Areas in Macaque Monkeys , 1996, The Journal of Neuroscience.

[103]  Gottfried Schlaug,et al.  Modulating activity in the motor cortex affects performance for the two hands differently depending upon which hemisphere is stimulated , 2008, The European journal of neuroscience.

[104]  Sergio P. Rigonatti,et al.  Transcranial direct current stimulation of the unaffected hemisphere in stroke patients , 2005, Neuroreport.

[105]  C. Calautti,et al.  Sequential activation brain mapping after subcortical stroke: changes in hemispheric balance and recovery , 2001, Neuroreport.

[106]  Julie Duque,et al.  Encoding a motor memory in the older adult by action observation , 2006, NeuroImage.

[107]  V. Hömberg,et al.  Reorganization of motor output in the non-affected hemisphere after stroke. , 1997, Brain : a journal of neurology.

[108]  Cornelius Weiller,et al.  Two different reorganization patterns after rehabilitative therapy: An exploratory study with fMRI and TMS , 2006, NeuroImage.

[109]  J. Donoghue,et al.  Dynamic organization of primary motor cortex output to target muscles in adult rats II. Rapid reorganization following motor nerve lesions , 2004, Experimental Brain Research.

[110]  J. Rothwell,et al.  Theta Burst Stimulation of the Human Motor Cortex , 2005, Neuron.

[111]  O. Witte,et al.  Extended brain disinhibition following small photothrombotic lesions in rat frontal cortex , 1997, Neuroreport.

[112]  Paolo Maria Rossini,et al.  Follow-up of interhemispheric differences of motor evoked potentials from the `affected' and `unaffected' hemispheres in human stroke , 1998, Brain Research.

[113]  R. Nudo,et al.  Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. , 1996, Journal of neurophysiology.

[114]  Christian Gerloff,et al.  The Role of Multiple Contralesional Motor Areas for Complex Hand Movements after Internal Capsular Lesion , 2006, The Journal of Neuroscience.

[115]  François Chollet,et al.  A longitudinal fMRI study: in recovering and then in clinically stable sub-cortical stroke patients , 2004, NeuroImage.

[116]  G. Schlaug,et al.  Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients , 2010, Neurology.

[117]  S. Barbay,et al.  Effects of small ischemic lesions in the primary motor cortex on neurophysiological organization in ventral premotor cortex. , 2006, Journal of neurophysiology.

[118]  Ichiro Watanabe,et al.  Repetitive Transcranial Magnetic Stimulation of Contralesional Primary Motor Cortex Improves Hand Function After Stroke , 2005, Stroke.

[119]  M Hallett,et al.  Mechanisms of Cortical Reorganization in Lower-Limb Amputees , 1998, The Journal of Neuroscience.

[120]  L. Cohen,et al.  Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke. , 2009, Stroke.

[121]  François Chollet,et al.  Correlation between cerebral reorganization and motor recovery after subcortical infarcts , 2003, NeuroImage.

[122]  S. Barbay,et al.  Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. , 2003, Journal of neurophysiology.

[123]  Katsunori Ikoma,et al.  Inhibition of the unaffected motor cortex by 1 Hz repetitive transcranical magnetic stimulation enhances motor performance and training effect of the paretic hand in patients with chronic stroke. , 2008, Journal of rehabilitation medicine.

[124]  Stephen E. Nadeau,et al.  Repetitive Transcranial Magnetic Stimulation as an Adjunct to Constraint-Induced Therapy: An Exploratory Randomized Controlled Trial , 2007, American journal of physical medicine & rehabilitation.

[125]  J. Krakauer Motor learning: its relevance to stroke recovery and neurorehabilitation. , 2006, Current opinion in neurology.

[126]  RP Dum,et al.  Topographic organization of corticospinal projections from the frontal lobe: motor areas on the lateral surface of the hemisphere , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[127]  Richard S. J. Frackowiak,et al.  The functional anatomy of motor recovery after stroke in humans: A study with positron emission tomography , 1991, Annals of neurology.

[128]  E. Khedr,et al.  Role of 1 and 3 Hz repetitive transcranial magnetic stimulation on motor function recovery after acute ischaemic stroke , 2009, European journal of neurology.

[129]  Hartwig R. Siebner,et al.  Modifying motor learning through gating and homeostatic metaplasticity , 2008, Brain Stimulation.

[130]  M. Rushworth,et al.  Functionally Specific Reorganization in Human Premotor Cortex , 2007, Neuron.

[131]  M. Hallett,et al.  Contribution of the ipsilateral motor cortex to recovery after chronic stroke , 2003, Annals of neurology.

[132]  J. Mullooly,et al.  Stroke in a defined elderly population, 1967-1985. A less lethal and disabling but no less common disease. , 1997, Stroke.

[133]  B R Rosen,et al.  A pilot study of somatotopic mapping after cortical infarct. , 2000, Stroke.

[134]  P M Rossini,et al.  Post-stroke reorganization of brain motor output to the hand: a 2-4 month follow-up with focal magnetic transcranial stimulation. , 1997, Electroencephalography and clinical neurophysiology.

[135]  G Schlaug,et al.  Repetitive TMS of the motor cortex improves ipsilateral sequential simple finger movements , 2004, Neurology.

[136]  M. Brainin,et al.  Neurostimulation in ischaemic stroke – down with the healthy hemisphere! , 2009, European journal of neurology.

[137]  W. Byblow,et al.  Functional potential in chronic stroke patients depends on corticospinal tract integrity. , 2006, Brain : a journal of neurology.

[138]  P. Matthews,et al.  The role of ipsilateral premotor cortex in hand movement after stroke , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[139]  Gereon R Fink,et al.  Effects of low-frequency repetitive transcranial magnetic stimulation of the contralesional primary motor cortex on movement kinematics and neural activity in subcortical stroke. , 2008, Archives of neurology.

[140]  P M Rossini,et al.  Neuroimaging experimental studies on brain plasticity in recovery from stroke. , 2007, Europa medicophysica.

[141]  S. Ibayashi,et al.  Deterioration of pre-existing hemiparesis brought about by subsequent ipsilateral lacunar infarction , 2003, Journal of neurology, neurosurgery, and psychiatry.