Review Article | Published:

Neuroplasticity in the context of motor rehabilitation after stroke

Nature Reviews Neurology volume 7, pages 7685 (2011) | Download Citation

Abstract

Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain–computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.

Key points

  • Training-based techniques, involving both physical and occupational therapy, continue to be the gold standard for poststroke motor rehabilitation

  • A better understanding of basic mechanisms of motor function and the pathophysiology of poststroke paresis will guide advances in neural repair and rehabilitation

  • Pharmacological, biological and electrophysiological techniques are being developed to augment neuroplasticity-induced and training-induced functional gains in patients with stroke

  • Exogenous cellular and neuroprosthetic technologies could enhance neural repair or offer alternative methods of motor control in patients with stroke

  • Combining measures of body function, activity, participation and patient quality of life will contribute to comprehensive goal setting in stroke rehabilitation

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References

  1. 1.

    et al. Contribution of chronic diseases to disability in elderly people in countries with low and middle incomes: a 10/66 Dementia Research Group population-based survey. Lancet 374, 1821–1830 (2009).

  2. 2.

    , , & Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science 272, 1791–1794 (1996).

  3. 3.

    , & New treatments in neurorehabilitation founded on basic research. Nat. Rev. Neurosci. 3, 228–236 (2002).

  4. 4.

    et al. Heart Disease and Stroke Statistics—2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 119, 480–486 (2008).

  5. 5.

    Motor learning: its relevance to stroke recovery and neurorehabilitation. Curr. Opin. Neurol. 19, 84–90 (2006).

  6. 6.

    How imaging will guide rehabilitation. Curr. Opin. Neurol. 23, 79–86 (2010).

  7. 7.

    & Contribution of transcranial magnetic stimulation to the understanding of functional recovery mechanisms after stroke. Neurorehabil. Neural Repair 24, 125–135 (2010).

  8. 8.

    & Recovery of function in humans: cortical stimulation and pharmacological treatments after stroke. Neurobiol. Dis. 37, 243–251 (2010).

  9. 9.

    & Cortical plasticity: from synapses to maps. Annu. Rev. Neurosci. 21, 149–186 (1998).

  10. 10.

    & Reconstructing functional systems after lesions of cerebral cortex. Nat. Rev. Neurosci. 2, 911–919 (2001).

  11. 11.

    et al. The reorganization of sensorimotor function in children after hemispherectomy. A functional MRI and somatosensory evoked potential study. Brain 123, 2432–2444 (2000).

  12. 12.

    , & Critical periods during sensory development. Curr. Opin. Neurobiol. 10, 138–145 (2000).

  13. 13.

    et al. Lack of long-term cortical reorganization after macaque retinal lesions. Nature 435, 300–307 (2005).

  14. 14.

    & Stem cells for the treatment of neurological disorders. Nature 441, 1094–1096 (2006).

  15. 15.

    , , & Adult cell therapy for brain neuronal damages and the role of tissue engineering. Biomaterials 31, 2105–2120 (2010).

  16. 16.

    , , , & Brain–computer interfaces for communication and control. Clin. Neurophysiol. 113, 767–791 (2002).

  17. 17.

    Disability: beyond the medical model. Lancet 374, 1793 (2009).

  18. 18.

    , , , & Music therapy for acquired brain injury. Cochrane Database of Systematic Reviews, Issue 7. Art. No.: CD006787. doi:10.1002/14651858.CD006787.pub2 (2010).

  19. 19.

    , , , & The impact of bilateral therapy on upper limb function after chronic stroke: a systematic review. Disabil. Rehabil. 32, 1221–1231 (2010).

  20. 20.

    et al. Does repetitive task training improve functional activity after stroke? A Cochrane systematic review and meta-analysis. J. Rehabil. Med. 42, 9–14 (2010).

  21. 21.

    Acute ischemic stroke management: administration of thrombolytics, neuroprotectants, and general principles of medical management. Neurol. Clin. 26, 943–961 (2008).

  22. 22.

    , , & Neuroprotection and stroke rehabilitation: modulation and enhancement of recovery. Behav. Neurol. 17, 17–24 (2006).

  23. 23.

    et al. Quality of stroke rehabilitation clinical practice guidelines. J. Eval. Clin. Pract. 13, 657–664 (2007).

  24. 24.

    et al. Evidence-based stroke rehabilitation: an expanded guidance document from the european stroke organisation (ESO) guidelines for management of ischaemic stroke and transient ischaemic attack 2008. J. Rehabil. Med. 41, 99–111 (2009).

  25. 25.

    et al. Veterans Affairs/Department of Defense Clinical Practice Guideline for the Management of Adult Stroke Rehabilitation Care: executive summary. Stroke 36, 2049–2056 (2005).

  26. 26.

    Confounders in rehabilitation trials of task-oriented training: lessons from the designs of the EXCITE and SCILT multicenter trials. Neurorehabil. Neural Repair 21, 3–13 (2007).

  27. 27.

    , , & Constraint-induced movement therapy for upper extremities in stroke patients. Cochrane Database Systematic Reviews, Issue 4. Art. No.: CD004433. doi:10.1002/14651858.CD004433.pub2 (2009).

  28. 28.

    & Constraint-induced movement therapy following stroke: a systematic review of randomised controlled trials. Aust. J. Physiother. 51, 221–231 (2005).

  29. 29.

    Evidence-based therapies for upper extremity dysfunction. Curr. Opin. Neurol. doi:10.1097/WCO.0b013e32833ff4c4.

  30. 30.

    Treadmill training with partial body weight support after stroke: a review. NeuroRehabilitation 23, 55–65 (2008).

  31. 31.

    , , & Treadmill training and body weight support for walking after stroke. Cochrane Database Systematic Reviews, Issue 4. Art. No.: CD002840. doi:10.1002/14651858.CD002840.pub2 (2005).

  32. 32.

    , , , & Cortical plasticity following motor skill learning during mental practice in stroke. Neurorehabil. Neural Repair 23, 382–388 (2009).

  33. 33.

    , & Motor imagery after stroke: relating outcome to motor network connectivity. Ann. Neurol. 66, 604–616 (2009).

  34. 34.

    , , , & Simultaneous bilateral training for improving arm function after stroke. Cochrane Database Systematic Reviews, Issue 4. Art. No.: CD006432. doi:10.1002/14651858.CD006432.pub2 (2010).

  35. 35.

    et al. Robotic devices as therapeutic and diagnostic tools for stroke recovery. Arch. Neurol. 66, 1086–1090 (2009).

  36. 36.

    et al. Robot-assisted therapy for long-term upper-limb impairment after stroke. N. Engl. J. Med. 362, 1772–1783 (2010).

  37. 37.

    , & Effects of robot-assisted therapy on upper limb recovery after stroke: a systematic review. Neurorehabil. Neural Repair 22, 111–121 (2008).

  38. 38.

    , & Virtual reality in stroke rehabilitation: a systematic review of its effectiveness for upper limb motor recovery. Top. Stroke Rehabil. 14, 52–61 (2007).

  39. 39.

    , , , & Efficacy of motor imagery in post-stroke rehabilitation: a systematic review. J. Neuroeng. Rehabil. 5, 8 (2008).

  40. 40.

    et al. Very early constraint-induced movement during stroke rehabilitation (VECTORS): a single-center RCT. Neurology 73, 195–201 (2009).

  41. 41.

    et al. Effect of constraint-induced movement therapy on upper extremity function 3 to 9 months after stroke: the EXCITE randomized clinical trial. JAMA 296, 2095–2104 (2006).

  42. 42.

    & Systematic reviews in rehabilitation for stroke: issues and approaches to addressing them. Clin. Rehabil. 16, 69–74 (2002).

  43. 43.

    , , , & In vivo voltage-sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites. J. Neurosci. 29, 1719–1734 (2009).

  44. 44.

    , & Synaptogenesis and dendritic growth in the cortex opposite unilateral sensorimotor cortex damage in adult rats: a quantitative electron microscopic examination. Brain Res. 733, 142–148 (1996).

  45. 45.

    et al. Extensive cortical rewiring after brain injury. J. Neurosci. 25, 10167–10179 (2005).

  46. 46.

    , , & Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury. Proc. Natl Acad. Sci. USA 98, 3513–3518 (2001).

  47. 47.

    Cellular and molecular mechanisms of neural repair after stroke: making waves. Ann. Neurol. 59, 735–742 (2006).

  48. 48.

    , & Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. Behav. Neural Biol. 44, 301–314 (1985).

  49. 49.

    , , & Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J. Neurosci. 19, 10153–10163 (1999).

  50. 50.

    , , & Learning-dependent synaptic modifications in the cerebellar cortex of the adult rat persist for at least four weeks. J. Neurosci. 17, 717–721 (1997).

  51. 51.

    , & Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke 26, 2135–2144 (1995).

  52. 52.

    & Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J. Neurosci. 21, 5272–5280 (2001).

  53. 53.

    , , & Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord. J. Appl. Physiol. 101, 1776–1782 (2006).

  54. 54.

    et al. Functional potential in chronic stroke patients depends on corticospinal tract integrity. Brain 130, 170–180 (2007).

  55. 55.

    , & Structural damage to the corticospinal tract correlates with bilateral sensorimotor cortex reorganization in stroke patients. Neuroimage 39, 1370–1382 (2008).

  56. 56.

    & The functional anatomy of cerebral reorganisation after focal brain injury. J. Physiol. Paris 99, 425–436 (2006).

  57. 57.

    Functional imaging of stroke recovery: what have we learnt and where do we go from here? Int. J. Stroke 2, 7–16 (2007).

  58. 58.

    Functional imaging of motor recovery after stroke: remaining challenges. Curr. Neurol. Neurosci. Rep. 4, 42–46 (2004).

  59. 59.

    et al. Evolution of cortical activation during recovery from corticospinal tract infarction. Stroke 31, 656–661 (2000).

  60. 60.

    , , , & Remote changes in cortical excitability after stroke. Brain 126, 470–481 (2003).

  61. 61.

    , , , & Motor cortical disinhibition during early and late recovery after stroke. Neurorehabil. Neural Repair 22, 396–403 (2008).

  62. 62.

    , , & Stages of motor output reorganization after hemispheric stroke suggested by longitudinal studies of cortical physiology. Cereb. Cortex 18, 1909–1922 (2008).

  63. 63.

    , , & Influence of interhemispheric interactions on motor function in chronic stroke. Ann. Neurol. 55, 400–409 (2004).

  64. 64.

    et al. Predicting functional gains in a stroke trial. Stroke 38, 2108–2114 (2007).

  65. 65.

    et al. Early imaging correlates of subsequent motor recovery after stroke. Ann. Neurol. 65, 596–602 (2009).

  66. 66.

    & Mechanisms underlying recovery of motor function after stroke. Arch. Neurol. 61, 1844–1848 (2004).

  67. 67.

    et al. Motor system activation after subcortical stroke depends on corticospinal system integrity. Brain 129, 809–819 (2006).

  68. 68.

    et al. Non-invasive mapping of corticofugal fibres from multiple motor areas—relevance to stroke recovery. Brain 129, 1844–1858 (2006).

  69. 69.

    et al. The role of ipsilateral premotor cortex in hand movement after stroke. Proc. Natl Acad. Sci. USA 99, 14518–14523 (2002).

  70. 70.

    What we can do and what we cannot do with fMRI. Nature 453, 869–878 (2008).

  71. 71.

    et al. The clinical diagnostic utility of transcranial magnetic stimulation: report of an IFCN committee. Clin. Neurophysiol. 119, 504–532 (2008).

  72. 72.

    et al. Neuroimaging in stroke recovery: a position paper from the First International Workshop on Neuroimaging and Stroke Recovery. Cerebrovasc. Dis. 18, 260–267 (2004).

  73. 73.

    & Biomarkers of recovery after stroke. Curr. Opin. Neurol. 21, 654–659 (2008).

  74. 74.

    et al. The future of restorative neurosciences in stroke: driving the translational research pipeline from basic science to rehabilitation of people after stroke. Neurorehabil. Neural Repair 23, 97–107 (2009).

  75. 75.

    Effects of delta-amphetamine on hemi-decorticate, decorticate, and decerebrate cats. Am. J. Physiol. 163, 731–732 (1950).

  76. 76.

    , & Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science 217, 855–857 (1982).

  77. 77.

    et al. Modulation of use-dependent plasticity by d-amphetamine. Ann. Neurol. 51, 59–68 (2002).

  78. 78.

    , , , & Enhancement of use-dependent plasticity by D-amphetamine. Neurology 59, 1262–1264 (2002).

  79. 79.

    , , , & Evidence that amphetamine with physical therapy promotes recovery of motor function in stroke patients. Ann. Neurol. 23, 94–97 (1988).

  80. 80.

    Amphetamine trials and tribulations. Stroke 40, S133–S135 (2009).

  81. 81.

    , & Amphetamines for improving recovery after stroke. Cochrane Database Systematic Reviews, Issue 3. Art. No.: CD002090. doi:10.1002/14651858.CD002090 (2003).

  82. 82.

    & Safety of dexamphetamine in acute ischemic stroke: a randomized, double-blind, controlled dose-escalation trial. Stroke 34, 475–481 (2003).

  83. 83.

    & The effects of amphetamine on recovery of function in animal models of cerebral injury: a critical appraisal. NeuroRehabilitation 25, 5–17 (2009).

  84. 84.

    , , & Effect of levodopa in combination with physiotherapy on functional motor recovery after stroke: a prospective, randomised, double-blind study. Lancet 358, 787–790 (2001).

  85. 85.

    & Effects of amphetamine and/or L-dopa and physiotherapy after stroke—a blinded randomized study. Acta Neurol. Scand. 115, 55–59 (2007).

  86. 86.

    Citicoline: update on a promising and widely available agent for neuroprotection and neurorepair. Rev. Neurol. Dis. 5, 167–177 (2008).

  87. 87.

    et al. An open-label pilot study of acetylcholinesterase inhibitors to promote functional recovery in elderly cognitively impaired stroke patients. Cerebrovasc. Dis. 26, 317–321 (2008).

  88. 88.

    Road to recovery: drugs used in stroke rehabilitation. Expert Rev. Neurother. 4, 219–231 (2004).

  89. 89.

    et al. Donepezil as an adjuvant to constraint-induced therapy for upper-limb dysfunction after stroke: an exploratory randomized clinical trial. J. Rehabil. Res. Dev. 41, 525–534 (2004).

  90. 90.

    et al. The clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; a Cochrane systematic review. Eur. J. Phys. Rehabil. Med. 45, 621–630 (2009).

  91. 91.

    , & A nerve growth-stimulating factor isolated from sarcom as 37 and 180. Proc. Natl Acad. Sci. USA 40, 1014–1018 (1954).

  92. 92.

    Are new neurons formed in the brains of adult mammals? Science 135, 1127–1128 (1962).

  93. 93.

    et al. Growth factor expression after stroke. Stroke 21 (Suppl. 11), 122–124 (1990).

  94. 94.

    Gene expression changes after focal stroke, traumatic brain and spinal cord injuries. Curr. Opin. Neurol. 16, 699–704 (2003).

  95. 95.

    & Regeneration of the adult central nervous system. Curr. Biol. 15, R749–R753 (2005).

  96. 96.

    , , & Electrical stimulation of the medullary pyramid promotes proliferation and differentiation of oligodendrocyte progenitor cells in the corticospinal tract of the adult rat. Neurosci. Lett. 479, 128–133 (2010).

  97. 97.

    & Promoting axonal rewiring to improve outcome after stroke. Neurobiol. Dis. 37, 259–266 (2010).

  98. 98.

    et al. Effects of granulocyte-colony stimulating factor after stroke in aged rats. Stroke 41, 1027–1031 (2010).

  99. 99.

    et al. Functional recovery of stroke rats induced by granulocyte colony-stimulating factor-stimulated stem cells. Circulation 110, 1847–1854 (2004).

  100. 100.

    et al. Meta-analysis of the efficacy of granulocyte-colony stimulating factor in animal models of focal cerebral ischemia. Stroke 39, 1855–1861 (2008).

  101. 101.

    , , & Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J. Neurosci. 21, 9733–9743 (2001).

  102. 102.

    et al. A novel neurotrophic therapeutic strategy for experimental stroke. Brain Res. 1280, 117–123 (2009).

  103. 103.

    et al. Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats. J. Cereb. Blood Flow Metab. 27, 983–997 (2007).

  104. 104.

    et al. Effect of brain-derived neurotrophic factor treatment and forced arm use on functional motor recovery after small cortical ischemia. Stroke 35, 992–997 (2004).

  105. 105.

    et al. Brain-derived neurotrophic factor contributes to recovery of skilled reaching after focal ischemia in rats. Stroke 40, 1490–1495 (2009).

  106. 106.

    et al. Brain-derived neurotrophic factor but not forced arm use improves long-term outcome after photothrombotic stroke and transiently upregulates binding densities of excitatory glutamate receptors in the rat brain. Stroke 39, 1012–1021 (2008).

  107. 107.

    et al. Recombinant human erythropoietin in the treatment of acute ischemic stroke. Stroke 40, e647–e656 (2009).

  108. 108.

    et al. The beta-hCG+erythropoietin in acute stroke (BETAS) study: a 3-center, single-dose, open-label, noncontrolled, phase IIa safety trial. Stroke 41, 927–931 (2010).

  109. 109.

    , , , & Influence of somatosensory input on interhemispheric interactions in patients with chronic stroke. Neurorehabil. Neural Repair 22, 477–485 (2008).

  110. 110.

    , & Increase in hand muscle strength of stroke patients after somatosensory stimulation. Ann. Neurol. 51, 122–125 (2002).

  111. 111.

    et al. Effects of somatosensory stimulation on motor function after subacute stroke. Neurorehabil. Neural Repair 24, 263–272 (2010).

  112. 112.

    & Afferent input and cortical organisation: a study with magnetic stimulation. Exp. Brain Res. 126, 536–544 (1999).

  113. 113.

    , , , & Functional MRI of human primary somatosensory and motor cortex during median nerve stimulation. Clin. Neurophysiol. 110, 47–52 (1999).

  114. 114.

    et al. Functional magnetic resonance image finding of cortical activation by neuromuscular electrical stimulation on wrist extensor muscles. Am. J. Phys. Med. Rehabil. 82, 17–20 (2003).

  115. 115.

    et al. Influence of somatosensory input on motor function in patients with chronic stroke. Ann. Neurol. 56, 206–212 (2004).

  116. 116.

    , & Neuromuscular electrical stimulation for motor restoration in hemiplegia. Top. Stroke Rehabil. 15, 412–426 (2008).

  117. 117.

    , , , & Functional electrical stimulation to dorsiflexors and plantar flexors during gait to improve walking in adults with chronic hemiplegia. Arch. Phys. Med. Rehabil. 91, 687–696 (2010).

  118. 118.

    , , & Interhemispheric competition after stroke: brain stimulation to enhance recovery of function of the affected hand. Neurorehabil. Neural Repair 23, 641–656 (2009).

  119. 119.

    et al. Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: a pilot study. Restor. Neurol. Neurosci. 25, 9–15 (2007).

  120. 120.

    , , & Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology 65, 466–468 (2005).

  121. 121.

    et al. Repetitive transcranial magnetic stimulation-induced corticomotor excitability and associated motor skill acquisition in chronic stroke. Stroke 37, 1471–1476 (2006).

  122. 122.

    , & Exploring theta burst stimulation as an intervention to improve motor recovery in chronic stroke. Clin. Neurophysiol. 118, 333–342 (2007).

  123. 123.

    et al. Repetitive transcranial magnetic stimulation as an adjunct to constraint-induced therapy: an exploratory randomized controlled trial. Am. J. Phys. Med. Rehabil. 86, 707–715 (2007).

  124. 124.

    et al. Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke. Stroke 40, 309–312 (2009).

  125. 125.

    et al. Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 128, 490–499 (2005).

  126. 126.

    et al. Effects of brain polarization on reaction times and pinch force in chronic stroke. BMC Neurosci. 7, 73 (2006).

  127. 127.

    & Improvement of motor function with noninvasive cortical stimulation in a patient with chronic stroke. Neurorehabil. Neural Repair 19, 14–19 (2005).

  128. 128.

    et al. Repeated sessions of noninvasive brain DC stimulation is associated with motor function improvement in stroke patients. Restor. Neurol. Neurosci. 25, 123–129 (2007).

  129. 129.

    et al. Recovery of upper-limb function due to enhanced use-dependent plasticity in chronic stroke patients. Brain 133, 3373–3384 (2010).

  130. 130.

    et al. Differential effects of high-frequency repetitive transcranial magnetic stimulation over ipsilesional primary motor cortex in cortical and subcortical middle cerebral artery stroke. Ann. Neurol. 66, 298–309 (2009).

  131. 131.

    , , & Motor cortex stimulation for enhancement of recovery after stroke: case report. Neurol. Res. 25, 815–818 (2003).

  132. 132.

    , , & Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study. Neurosurgery 58, 464–473 (2006).

  133. 133.

    et al. Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: a multicenter feasibility study of safety and efficacy. J. Neurosurg. 108, 707–714 (2008).

  134. 134.

    Neuroregeneration enhanced by transcranial direct current current stimulation (TDCS) in stroke NCT00909714. US NIH ClinicalTrials.gov , (2010).

  135. 135.

    et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66, 198–204 (2010).

  136. 136.

    , , & Pharmacological approach to the mechanisms of transcranial DC-stimulation-induced after-effects of human motor cortex excitability. Brain 125, 2238–2247 (2002).

  137. 137.

    , , & Striatal dopamine release induced by repetitive transcranial magnetic stimulation of the human motor cortex. Brain 126, 2609–2615 (2003).

  138. 138.

    et al. GABAergic modulation of DC stimulation-induced motor cortex excitability shifts in humans. Eur. J. Neurosci. 19, 2720–2726 (2004).

  139. 139.

    & Transcranial magnetic stimulation: new insights into representational cortical plasticity. Exp. Brain Res. 148, 1–16 (2003).

  140. 140.

    , , & Neural correlates of motor recovery after stroke: a longitudinal fMRI study. Brain 126, 2476–2496 (2003).

  141. 141.

    et al. The role of multiple contralesional motor areas for complex hand movements after internal capsular lesion. J. Neurosci. 26, 6096–6102 (2006).

  142. 142.

    et al. Multimodal imaging of brain reorganization in motor areas of the contralesional hemisphere of well recovered patients after capsular stroke. Brain 129, 791–808 (2006).

  143. 143.

    et al. Imaging correlates of motor recovery from cerebral infarction and their physiological significance in well-recovered patients. Neuroimage 34, 253–263 (2007).

  144. 144.

    et al. Transcallosal inhibition in chronic subcortical stroke. Neuroimage 28, 940–946 (2005).

  145. 145.

    Hemi-neglect and hemisphere rivalry. Adv. Neurol. 18, 41–49 (1977).

  146. 146.

    , , , & Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke 36, 2681–2686 (2005).

  147. 147.

    et al. A sham stimulation-controlled trial of rTMS of the unaffected hemisphere in stroke patients. Neurology 64, 1802–1804 (2005).

  148. 148.

    et al. A sham-controlled trial of a 5-day course of repetitive transcranial magnetic stimulation of the unaffected hemisphere in stroke patients. Stroke 37, 2115–2122 (2006).

  149. 149.

    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. Arch. Neurol. 65, 741–747 (2008).

  150. 150.

    et al. Contralesional repetitive transcranial magnetic stimulation for chronic hemiparesis in subcortical paediatric stroke: a randomised trial. Lancet Neurol. 7, 507–513 (2008).

  151. 151.

    , & 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. Restor. Neurol. Neurosci. 25, 461–465 (2007).

  152. 152.

    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. J. Rehabil. Med. 40, 298–303 (2008).

  153. 153.

    , , & Combining theta burst stimulation with training after subcortical stroke. Stroke 41, 1568–1572 (2010).

  154. 154.

    , , , & Effects of combined peripheral nerve stimulation and brain polarization on performance of a motor sequence task after chronic stroke. Stroke 40, 1764–1771 (2009).

  155. 155.

    , & Effect of consecutive application of paired associative stimulation on motor recovery in a rat stroke model: a preliminary study. Int. J. Neurosci. 118, 807–820 (2008).

  156. 156.

    et al. Induction of cortical plastic changes in wrist muscles by paired associative stimulation in the recovery phase of stroke patients. Neurorehabil. Neural Repair 23, 366–372 (2009).

  157. 157.

    , , , & Induction of cortical plastic changes in wrist muscles by paired associative stimulation in healthy subjects and post-stroke patients. Exp. Brain Res. 180, 113–122 (2007).

  158. 158.

    & Contralesional paired associative stimulation increases paretic lower limb motor excitability post-stroke. Exp. Brain Res. 185, 563–570 (2008).

  159. 159.

    et al. Modulating cortical connectivity in stroke patients by rTMS assessed with fMRI and dynamic causal modeling. Neuroimage 50, 233–242 (2010).

  160. 160.

    & Mechanisms underlying functional changes in the primary motor cortex ipsilateral to an active hand. J. Neurosci. 28, 5631–5640 (2008).

  161. 161.

    & Stem cells in human neurodegenerative disorders—time for clinical translation? J. Clin. Invest. 120, 29–40 (2010).

  162. 162.

    Pilot investigation of stem cells in stroke (PISCES) NCT01151124. US NIH ClinicalTrials.gov , (2010).

  163. 163.

    et al. Transplantation of human neural precursor cells in Matrigel scaffolding improves outcome from focal cerebral ischemia after delayed postischemic treatment in rats. J. Cereb. Blood Flow Metab. 30, 534–544 (2010).

  164. 164.

    et al. Hydrogel matrix to support stem cell survival after brain transplantation in stroke. Neurorehabil. Neural Repair 24, 636–644 (2010).

  165. 165.

    & Nanotechnology for treatment of stroke and spinal cord injury. Nanomedicine (Lond.) 5, 99–108 (2010).

  166. 166.

    & Brain-computer interfaces in neurological rehabilitation. Lancet Neurol. 7, 1032–1043 (2008).

  167. 167.

    et al. Think to move: a neuromagnetic brain–computer interface (BCI) system for chronic stroke. Stroke 39, 910–917 (2008).

  168. 168.

    et al. Neural interface technology for rehabilitation: exploiting and promoting neuroplasticity. Phys. Med. Rehabil. Clin. N. Am. 21, 157–178 (2010).

  169. 169.

    et al. Feasibility of a new application of noninvasive brain computer interface (BCI): a case study of training for recovery of volitional motor control after stroke. J. Neurol. Phys. Ther. 33, 203–211 (2009).

  170. 170.

    et al. Combination of brain-computer interface training and goal-directed physical therapy in chronic stroke: a case report. Neurorehabil. Neural Repair 24, 674–679 (2010).

  171. 171.

    The optogenetic catechism. Science 326, 395–399 (2009).

  172. 172.

    et al. Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141, 154–165 (2010).

  173. 173.

    et al. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66, 681–694 (2010).

  174. 174.

    et al. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nat. Neurosci. 9, 735–737 (2006).

  175. 175.

    , , & Mapping genetic influences on the corticospinal motor system in humans. Neuroscience 164, 156–163 (2009).

  176. 176.

    International classification of functioning, disability and health: an introduction and discussion of its potential impact on rehabilitation services and research. J. Rehabil. Med. 34, 201–204 (2002).

  177. 177.

    The first year of rehabilitation after a stroke—from two perspectives. Scand. J. Caring Sci. 17, 215–222 (2003).

  178. 178.

    , , , & Stroke patients' and therapists' opinions of constraint-induced movement therapy. Clin. Rehabil. 16, 55–60 (2002).

  179. 179.

    et al. Relationships between long-term stroke disability, handicap and health-related quality of life. Age Ageing 35, 273–279 (2006).

  180. 180.

    , , & Measuring quality of life in a way that is meaningful to stroke patients. Neurology 53, 1839–1843 (1999).

  181. 181.

    , & What do motor “recovery” and “compensation” mean in patients following stroke? Neurorehabil. Neural Repair 23, 313–319 (2009).

  182. 182.

    et al. Relationship of the Met allele of the brain-derived neurotrophic factor Val66Met polymorphism to memory after aneurysmal subarachnoid hemorrhage. Neurosurgery 63, 198–203 (2008).

  183. 183.

    et al. BDNF genotype potentially modifying the association between incident stroke and depression. Neurobiol. Aging 29, 789–792 (2008).

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Acknowledgements

This work was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, NIH. The original illustrations used for Figure 1 were by G. Qushair of SciLingua.

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Affiliations

  1. Human Cortical Physiology and Stroke Neurorehabilitation Section, National Institute of Neurological Disorders and Stroke, NIH, 10 Center Drive MSC 1428, Bethesda, MD 20892-1428, USA

    • Michael A. Dimyan
    •  & Leonardo G. Cohen

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Contributions

M. A. Dimyan and L. G. Cohen researched the data and wrote the article, and provided substantial contributions to discussions of the content, reviewing and editing of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Leonardo G. Cohen.

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DOI

https://doi.org/10.1038/nrneurol.2010.200