Nothing Special   »   [go: up one dir, main page]

Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neuroscience insights improve neurorehabilitation of poststroke aphasia

Abstract

The treatment of aphasias—acquired language disorders—caused by stroke and other neurological conditions has benefitted from insights from neuroscience and neuropsychology. Hebbian mechanisms suggest that massed practice and exploitation of residual neurological capacities can aid neurorehabilitation of patients with poststroke aphasia, and progress in basic neuroscience research indicates that the language system of the human brain is functionally interwoven with perceptual and motor systems. Intensive speech and language therapies, including constraint-induced aphasia therapy, that activate both the linguistic and concordant motor circuits utilize the knowledge gained from these advances in neuroscience research and can lead to surprisingly rapid improvements in language performance, even in patients with chronic aphasia. Drug-based therapies alone and in conjunction with behavioral language therapies also increase language performance in patients with aphasia. Furthermore, noninvasive transcranial magnetic stimulation and electrical stimulation techniques that target neuronal activity within perilesional areas might help patients with aphasia to regain lost language functions. Intensive language–action therapies that lead to rapid improvements in language skills might provide a new opportunity for investigating fast plastic neuronal changes in the areas of the brain associated with language processing. Here, we review progress in basic neuroscience research and its translational impact on the neurorehabilitation of language disorders after stroke.

Key Points

  • Advances in neuroscience research have led to the development of novel treatments for poststroke aphasia

  • Intensive language–action therapy, pharmacological interventions and noninvasive brain stimulation can enhance language performance in patients with poststroke aphasia

  • Intensive language–action therapy can improve language performance of patients with aphasia several years after a stroke episode

  • Constraint-induced aphasia therapy is more effective than conventional speech–language therapy at treating chronic poststroke aphasia

  • Drug therapies targeting linguistic and cognitive disorders can augment functional improvements associated with intensive language–action therapy

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Brain areas involved in language processing.
Figure 2: CIAT for chronic poststroke aphasia.
Figure 3: Selected brainstem and basal forebrain nuclei and their major ascending monoaminergic and cholinergic projections.
Figure 4: Changes in brain activity over 2 weeks of CIAT in patients with chronic poststroke aphasia.

Similar content being viewed by others

References

  1. Engelter, S. T. et al. Epidemiology of aphasia attributable to first ischemic stroke: incidence, severity, fluency, etiology, and thrombolysis. Stroke 37, 1379–1384 (2006).

    Article  PubMed  Google Scholar 

  2. Dickey, L. et al. Incidence and profile of inpatient stroke-induced aphasia in Ontario, Canada. Arch. Phys. Med. Rehabil. 91, 196–202 (2010).

    Article  PubMed  Google Scholar 

  3. Law, J. et al. Reconciling the perspective of practitioner and service user: findings from The Aphasia in Scotland study. Int. J. Lang. Commun. Disord. 45, 551–560 (2009).

    Article  Google Scholar 

  4. Pedersen, P. M., Vinter, K. & Olsen, T. S. Aphasia after stroke: type, severity and prognosis. The Copenhagen aphasia study. Cerebrovasc. Dis. 17, 35–43 (2004).

    Article  PubMed  Google Scholar 

  5. Lazar, R. M. & Antoniello, D. Variability in recovery from aphasia. Curr. Neurol. Neurosci. 8, 497–502 (2008).

    Article  Google Scholar 

  6. Lazar, R. M. et al. Improvement in aphasia scores after stroke is well predicted by initial severity. Stroke 41, 1485–1488 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  7. Starkstein, S. E. & Robinson, R. G. Depression and aphasia. Aphasiology 2, 1–20 (1988).

    Article  Google Scholar 

  8. Gonzalez Rothi, L. J. & Barrett, A. M. The changing view of neurorehabilitation: a new era of optimism. J. Int. Neuropsychol. Soc. 12, 812–815 (2006).

    PubMed  Google Scholar 

  9. Taub, E., Uswatte, G. & Elbert, T. New treatments in neurorehabilitation founded on basic research. Nat. Rev. Neurosci. 3, 228–236 (2002).

    Article  CAS  PubMed  Google Scholar 

  10. Merzenich, M. M. et al. Temporal processing deficits of language-learning impaired children ameliorated by training. Science 271, 77–81 (1996).

    Article  CAS  PubMed  Google Scholar 

  11. Astrup, J., Siesjo, B. K. & Symon, L. Thresholds in cerebral ischemia—the ischemic penumbra. Stroke 12, 723–725 (1981).

    Article  CAS  PubMed  Google Scholar 

  12. Hillis, A. E. Pharmacological, surgical, and neurovascular interventions to augment acute aphasia recovery. Am. J. Phys. Med. Rehab. 86, 426–434 (2007).

    Article  Google Scholar 

  13. Cramer, S. C. Repairing the human brain after stroke. II. Restorative therapies. Ann. Neurol. 63, 549–560 (2008).

    Article  PubMed  Google Scholar 

  14. Cramer, S. C. & Riley, J. D. Neuroplasticity and brain repair after stroke. Curr. Opin. Neurol. 21, 76–82 (2008).

    Article  PubMed  Google Scholar 

  15. Hebb, D. O. The Organization of Behavior. A Neuropsychological Theory (John Wiley, New York, 1949).

    Google Scholar 

  16. Bi, G. Q. Spatiotemporal specificity of synaptic plasticity: cellular rules and mechanisms. Biol. Cybern. 87, 319–332 (2002).

    Article  PubMed  Google Scholar 

  17. Tsumoto, T. Long-term potentiation and long-term depression in the neocortex. Prog. Neurobiol. 39, 209–228 (1992).

    Article  CAS  PubMed  Google Scholar 

  18. Basso, A. How intensive/prolonged should be an intensive/prolonged treatment be? Aphasiology 19, 975–984 (2005).

    Article  Google Scholar 

  19. Bakheit, A. M. et al. A prospective, randomized, parallel group, controlled study of the effect of intensity of speech and language therapy on early recovery from poststroke aphasia. Clin. Rehabil. 21, 885–894 (2007).

    Article  CAS  PubMed  Google Scholar 

  20. Pulvermüller, F., Hummel, F. & Härle, M. Walking or talking? Behavioral and neurophysiological correlates of action verb processing. Brain Lang. 78, 143–168 (2001).

    Article  PubMed  Google Scholar 

  21. Hauk, O., Johnsrude, I. & Pulvermüller, F. Somatotopic representation of action words in the motor and premotor cortex. Neuron 41, 301–307 (2004).

    Article  CAS  PubMed  Google Scholar 

  22. Kemmerer, D., Castillo, J. G., Talavage, T., Patterson, S. & Wiley, C. Neuroanatomical distribution of five semantic components of verbs: evidence from fMRI. Brain Lang. 107, 16–43 (2008).

    Article  PubMed  Google Scholar 

  23. Pulvermüller, F., Shtyrov, Y. & Ilmoniemi, R. J. Brain signatures of meaning access in action word recognition. J. Cog. Neurosci. 17, 884–892 (2005).

    Article  Google Scholar 

  24. Pulvermüller, F., Hauk, O., Nikulin, V. V. & Ilmoniemi, R. J. Functional links between motor and language systems. Eur. J. Neurosci. 21, 793–797 (2005).

    Article  PubMed  Google Scholar 

  25. Glenberg, A. M. & Kaschak, M. P. Grounding language in action. Psychon. Bull. Rev. 9, 558–565 (2002).

    Article  PubMed  Google Scholar 

  26. Glenberg, A. M., Sato, M. & Cattaneo, L. Use-induced motor plasticity affects the processing of abstract and concrete language. Curr. Biol. 18, R290–R291 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Fischer, M. H. & Zwaan, R. A. Embodied language: a review of the role of the motor system in language comprehension. Q. J. Exp. Psychol. (Colchester) 61, 825–850 (2008).

    Article  Google Scholar 

  28. Moscoso Del Prado Martin, F., Hauk, O. & Pulvermüller, F. Category specificity in the processing of color-related and form-related words: an ERP study. Neuroimage 29, 29–37 (2006).

    Article  PubMed  Google Scholar 

  29. Gonzalez, J. et al. Reading “cinnamon” activates olfactory brain regions. Neuroimage 32, 906–912 (2006).

    Article  PubMed  Google Scholar 

  30. Kiefer, M., Sim, E. J., Herrnberger, B., Grothe, J. & Hoenig, K. The sound of concepts: four markers for a link between auditory and conceptual brain systems. J. Neurosci. 28, 12224–12230 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Martin, A. The representation of object concepts in the brain. Annu. Rev. Psychol. 58, 25–45 (2007).

    Article  PubMed  Google Scholar 

  32. Tranel, D., Damasio, H. & Damasio, A. R. A neural basis for the retrieval of conceptual knowledge. Neuropsychologia 35, 1319–1327 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. Pulvermüller, F. & Fadiga, L. Active perception: sensorimotor circuits as a cortical basis for language. Nat. Rev. Neurosci. 11, 351–360 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Bak, T. H., O'Donovan, D. G., Xuereb, J. H., Boniface, S. & Hodges, J. R. Selective impairment of verb processing associated with pathological changes in Brodmann areas 44 and 45 in the motor neuron disease-dementia-aphasia syndrome. Brain 124, 103–120 (2001).

    Article  CAS  PubMed  Google Scholar 

  35. Neininger, B. & Pulvermüller, F. Word-category specific deficits after lesions in the right hemisphere. Neuropsychologia 41, 53–70 (2003).

    Article  PubMed  Google Scholar 

  36. Pulvermüller, F. Brain mechanisms linking language and action. Nat. Rev. Neurosci. 6, 576–582 (2005).

    Article  CAS  PubMed  Google Scholar 

  37. Berman, A. J., Teodoru, D. & Taub, E. Conditioned behavior following sensory isolation in primates. Trans. Am. Neurol. Assoc. 89, 185–186 (1964).

    CAS  PubMed  Google Scholar 

  38. Kolk, H. H. J. & Heeschen, C. Adaptation symptoms and impairment symptoms in Broca's aphasia. Aphasiology 4, 221–231 (1990).

    Article  Google Scholar 

  39. Pulvermüller, F. & Berthier, M. L. Aphasia therapy on a neuroscience basis. Aphasiology 22, 563–599 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Aten, J. L., Caligiuri, M. P. & Holland, A. L. The efficacy of functional communication therapy for chronic aphasic patients. J. Speech Hear. Disord. 47, 93–96 (1982).

    Article  CAS  PubMed  Google Scholar 

  41. Davis, G. A. & Wilcox, M. J. Adult Aphasia Rehabilitation: Applied Pragmatics (College Hill Press, San Diego, 1985).

    Google Scholar 

  42. Pulvermüller, F. & Roth, V. M. Communicative aphasia treatment as a further development of PACE therapy. Aphasiology 5, 39–50 (1991).

    Article  Google Scholar 

  43. Taub, E., Crago, J. E. & Uswatte, G. Constraint-induced movement therapy: a new approach to treatment in physical rehabilitation. Rehab. Psychol. 43, 152–170 (1998).

    Article  Google Scholar 

  44. Miltner, W. H., Bauder, H., Sommer, M., Dettmers, C. & Taub, E. Effects of constraint-induced movement therapy on patients with chronic motor deficits after stroke: a replication. Stroke 30, 586–592 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. Broida, H. Language therapy effects in long term aphasia. Arch. Phys. Med. Rehabil. 58, 248–253 (1977).

    CAS  PubMed  Google Scholar 

  46. Basso, A., Capitani, E. & Vignolo, L. A. Influence of rehabilitation on language skills in aphasic patients. A controlled study. Arch. Neurol. 36, 190–196 (1979).

    Article  CAS  PubMed  Google Scholar 

  47. Lincoln, N. B. et al. Effectiveness of speech therapy for aphasic stroke patients: a randomized controlled trial. Lancet 1, 1197–1200 (1984).

    Article  CAS  PubMed  Google Scholar 

  48. Howard, D., Patterson, K., Franklin, S., Orchard-Lisle, V. & Morton, J. Treatment of word retrieval deficits in aphasia. A comparison of two therapy methods. Brain 108, 817–829 (1985).

    Article  PubMed  Google Scholar 

  49. Doesborgh, S. J. et al. Effects of semantic treatment on verbal communication and linguistic processing in aphasia after stroke: a randomized controlled trial. Stroke 35, 141–146 (2004).

    Article  PubMed  Google Scholar 

  50. Glogowska, M., Roulstone, S., Enderby, P. & Peters, T. J. Randomised controlled trial of community based speech and language therapy in preschool children. BMJ 321, 923–926 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Katz, R. C. & Wertz, R. T. The efficacy of computer-provided reading treatment for chronic aphasic adults. J. Speech Lang. Hear. Res. 40, 493–507 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Robey, R. R. A meta-analysis of clinical outcomes in the treatment of aphasia. J. Speech Lang. Hear. Res. 41, 172–187 (1998).

    Article  CAS  PubMed  Google Scholar 

  53. Holland, A. L., Fromm, D. S., DeRuyter, F. & Stein, M. Treatment efficacy: aphasia. J. Speech Hear. Res. 39, S27–S36 (1996).

    Article  CAS  PubMed  Google Scholar 

  54. Greener, J., Enderby, P., Whurr, R. & Grant, A. Treatment for aphasia following stroke: evidence for effectiveness. Int. J. Lang. Commun. Disord. 33 (Suppl.), 158–161 (1998).

    Article  PubMed  Google Scholar 

  55. Pulvermüller, F. & Schönle, P. W. Behavioral and neuronal changes during treatment of mixed-transcortical aphasia: a case study. Cognition 48, 139–161 (1993).

    Article  PubMed  Google Scholar 

  56. Basso, A. & Caporali, A. Aphasia therapy or the importance of being earnest. Aphasiology 15, 307–332 (2001).

    Article  Google Scholar 

  57. Pulvermüller, F. et al. Constraint-induced therapy of chronic aphasia following stroke. Stroke 32, 1621–1626 (2001).

    Article  PubMed  Google Scholar 

  58. Meinzer, M. et al. Intensive training enhances brain plasticity in chronic aphasia. BMC Biol. 2, 20 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Meinzer, M., Djundja, D., Barthel, G., Elbert, T. & Rockstroh, B. Long-term stability of improved language functions in chronic aphasia after constraint-induced aphasia therapy. Stroke 36, 1462–1466 (2005).

    Article  PubMed  Google Scholar 

  60. Pulvermüller, F., Hauk, O., Zohsel, K., Neininger, B. & Mohr, B. Therapy-related reorganization of language in both hemispheres of patients with chronic aphasia. Neuroimage 28, 481–489 (2005).

    Article  PubMed  Google Scholar 

  61. Maher, L. M. et al. A pilot study of use-dependent learning in the context of constraint induced language therapy. J. Int. Neuropsychol. Soc. 12, 843–852 (2006).

    Article  PubMed  Google Scholar 

  62. Breier, J. I., Maher, L. M., Novak, B. & Papanicolaou, A. C. Functional imaging before and after constraint-induced language therapy for aphasia using magnetoencephalography. Neurocase 12, 322–331 (2006).

    Article  PubMed  Google Scholar 

  63. Meinzer, M., Streiftau, S. & Rockstroh, B. Intensive language training in the rehabilitation of chronic aphasia: efficient training by laypersons. J. Int. Neuropsychol. Soc. 13, 846–853 (2007).

    Article  PubMed  Google Scholar 

  64. Breier, J. I., Maher, L. M., Schmadeke, S., Hasan, K. M. & Papanicolaou, A. C. Changes in language-specific brain activation after therapy for aphasia using magnetoencephalography: a case study. Neurocase 13, 169–177 (2007).

    Article  PubMed  Google Scholar 

  65. Meinzer, M. et al. Functional re-recruitment of dysfunctional brain areas predicts language recovery in chronic aphasia. Neuroimage 39, 2038–2046 (2008).

    Article  PubMed  Google Scholar 

  66. Richter, M., Miltner, W. H. & Straube, T. Association between therapy outcome and right-hemispheric activation in chronic aphasia. Brain 131, 1391–1401 (2008).

    Article  PubMed  Google Scholar 

  67. Szaflarski, J. P. et al. Constraint-induced aphasia therapy stimulates language recovery in patients with chronic aphasia after ischemic stroke. Med. Sci. Monit. 14, CR243–CR250 (2008).

    PubMed  Google Scholar 

  68. Barthel, G., Meinzer, M., Djundja, D. & Rockstroh, B. Intensive language therapy in chronic aphasia: which aspects contribute most? Aphasiology 22, 408–421 (2008).

    Article  Google Scholar 

  69. Breier, J. I. et al. Behavioral and neurophysiologic response to therapy for chronic aphasia. Arch. Phys. Med. Rehabil. 90, 2026–2033 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Berthier, M. L. et al. Memantine and constraint-induced aphasia therapy in chronic poststroke aphasia. Ann. Neurol. 65, 577–585 (2009).

    Article  CAS  PubMed  Google Scholar 

  71. Goral, M. & Kempler, D. Training verb production in communicative context: evidence from a person with chronic non-fluent aphasia. Aphasiology 23, 1383–1397 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Faroqi-Shah, Y. & Virion, C. R. Constraint-induced language therapy for agrammatism: role of grammatical constraints. Aphasiology 23, 977–988 (2009).

    Article  Google Scholar 

  73. Kirmess, M. & Maher, L. M. Constraint induced language therapy in early aphasia rehabilitation. Aphasiology 24, 725–736 (2010).

    Article  Google Scholar 

  74. Bhogal, S. K., Teasell, R. & Speechley, M. Intensity of aphasia therapy, impact on recovery. Stroke 34, 987–993 (2003).

    Article  PubMed  Google Scholar 

  75. Cherney, L. R. et al. Evidence-based systematic review: effects of intensity of treatment and constraint-induced language therapy for individual with stroke-induced aphasia. J. Speech Lang. Hear. Res. 51, 1282–1299 (2008).

    Article  PubMed  Google Scholar 

  76. Kelly, H., Brady, M. C. & Enderby, P. Speech and language therapy for aphasia following stroke. Cochrane Database of Systematic Reviews, Issue 5. Art. No.: CD000425. doi: 10.1002/14651858.CD000425.pub2 (2010).

  77. Cramer, S. C., Shah, R., Juranek, J., Crafton, K. R. & Le, V. Activity in the peri-infarct rim in relation to recovery from stroke. Stroke 37, 111–115 (2006).

    Article  PubMed  Google Scholar 

  78. Hansen, A. J. & Zeuthen, T. Extracellular ion concentrations during spreading depression and ischemia in the rat brain cortex. Acta Physiol. Scand. 113, 437–445 (1981).

    Article  CAS  PubMed  Google Scholar 

  79. Kamada, K. et al. Functional and metabolic analysis of cerebral ischemia using magnetoencephalography and proton magnetic resonance spectroscopy. Ann. Neurol. 42, 554–563 (1997).

    Article  CAS  PubMed  Google Scholar 

  80. Lewine, J. D. et al. Objective documentation of traumatic brain injury subsequent to mild head trauma: multimodal brain imaging with MEG, SPECT, and MRI. J. Head Trauma Rehabil. 22, 141–155 (2007).

    Article  PubMed  Google Scholar 

  81. Witte, O. W., Bidmon, H. J., Schiene, K., Redecker, C. & Hagemann, G. Functional differentiation of multiple perilesional zones after focal cerebral ischemia. J. Cereb. Blood Flow Metab. 20, 1149–1165 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. Albert, M. L., Bachman, D. & Morgan, A. & Helm-Estabrooks, N. Pharmacotherapy for aphasia. Neurology 38, 877–879 (1988).

    Article  CAS  PubMed  Google Scholar 

  83. Bakheit, A. M. Drug treatment of poststroke aphasia. Expert Rev. Neurother. 4, 211–217 (2004).

    Article  CAS  PubMed  Google Scholar 

  84. Klein, R. B. & Albert, M. L. Can drug therapies improve language functions of individual with aphasia? A review of the evidence. Semin. Speech Lang. 25, 193–204 (2004).

    Article  PubMed  Google Scholar 

  85. McNamara, P. & Albert, M. L. Neuropharmacology of verbal perseveration. Semin. Speech Lang. 25, 309–321 (2004).

    Article  PubMed  Google Scholar 

  86. Berthier, M. L. Poststroke aphasia: epidemiology, pathophysiology and treatment. Drugs Aging 22, 163–182 (2005).

    Article  CAS  PubMed  Google Scholar 

  87. de Boissezon, X., Peran, P., de Boysson, C. & Démonet, J. F. Pharmacotherapy of aphasia: myth or reality? Brain Lang. 102, 114–125 (2007).

    Article  PubMed  Google Scholar 

  88. Crinion, J. T. & Leff, A. P. Recovery and treatment of aphasia after stroke: functional imaging studies. Curr. Opin. Neurol. 20, 667–673 (2007).

    Article  PubMed  Google Scholar 

  89. Liepert, J. Pharmacotherapy in restorative neurology. Curr. Opin. Neurol. 21, 639–643 (2008).

    Article  CAS  PubMed  Google Scholar 

  90. Small, S. L. & Llano, D. A. Biological approaches to aphasia treatment. Curr. Neurol. Neurosci. Rep. 9, 443–450 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  92. Gundersen, V. Co-localization of excitatory and inhibitory transmitters in the brain. Acta Neurol. Scand. Suppl. 188, 29–33 (2008).

    Article  CAS  PubMed  Google Scholar 

  93. Mesulam, M. M. The cholinergic innervation of the human cerebral cortex. Prog. Brain Res. 145, 68–78 (2004).

    Google Scholar 

  94. Goldman-Rakic, P. S., Lidow, M. S. & Gallager, D. W. Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex. J. Neurosci. 10, 2125–2138 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Luria, A., Naydyn, V. L., Tsvetkova, L. S. & Vinarskaya, E. N. Restoration of higher cortical function following local brain damage. In Handbook of Clinical Neurology (eds Vinken, P. J. & Bruyn, G. W.) 368–433 (North-Holland Publishing Company, Amsterdam, 1969).

    Google Scholar 

  96. Winblad, B. Piracetam: a review of pharmacological properties and clinical uses. CNS Drug Rev. 11, 169–182 (2005).

    Article  CAS  PubMed  Google Scholar 

  97. Huber, W. The role of piracetam in the treatment of acute and chronic aphasia. Pharmacopsychiatry 32 (Suppl. 1), 38–43 (1999).

    Article  CAS  PubMed  Google Scholar 

  98. Kessler, J., Thiel, A., Karbe, H. & Heiss, W. D. Piracetam improves activated blood flow and facilitates rehabilitation of poststroke aphasic patients. Stroke 31, 2112–2116 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Grenner, J., Enderby, P. & Whurr, R. Pharmacological treatment for aphasia following stroke. Cochrane Database of Systematic Reviews, Issue 4. Art. No.: CD000424. doi: 10.1002/14651858.CD000424 (2001).

  100. Walker-Batson, D. et al. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 32, 2093–2098 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Seniów, J., Litwin, M., Litwin, T., Lesniak, M. & Czlonkowska, A. New approach to the rehabilitation of post-stroke focal cognitive syndrome: effect of levodopa combined with speech and language therapy on functional recovery from aphasia. J. Neurol. Sci. 283, 214–218 (2009).

    Article  PubMed  Google Scholar 

  102. Barrett, A. M. & Eslinger, P. J. Amantadine for adynamic speech: possible benefit for aphasia. Am. J. Phys. Med. Rehabil. 86, 605–612 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Leiguarda, R., Merello, M., Sabe, L. & Starkstein, S. Bromocriptine-induced dystonia in patients with aphasia and hemiparesis. Neurology 43, 2319–2322 (1993).

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

    PubMed  PubMed Central  Google Scholar 

  105. Goldstein, L. B. Amphetamine trials and tribulations. Stroke 40, S133–S135 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Martinsson, L., Wahlgreen, N. G. & Hardemark, H. G. Amphetamines for improving recovery after stroke. Cochrane Database of Systematic Reviews, Issue 3. Art. No.: CD002090. doi: 10.1002/14651858.CD002090 (2003).

  107. Raymer, A. M. Treatment of adynamia in aphasia. Front. Biosci. 8, s845–s851 (2003).

    Article  CAS  PubMed  Google Scholar 

  108. Sabe, L., Leiguarda, R. & Starkstein, S. An open-label trial of bromocriptine in nonfluent aphasia. Neurology 42, 1637–1638 (1992).

    Article  CAS  PubMed  Google Scholar 

  109. Gupta, S. & Mlcoch, A. Bromocriptine treatment of nonfluent aphasia. Arch. Phys. Med. Rehabil. 73, 373–376 (1992).

    Article  CAS  PubMed  Google Scholar 

  110. Sabe, L., Salvarezza, F., García Cuerva, A., Leiguarda, R. & Starkstein, S. A randomized, double-blind, placebo-controlled study of bromocriptine in nonfluent aphasia. Neurology 45, 2272–2274 (1995).

    Article  CAS  PubMed  Google Scholar 

  111. Ozeren, A., Sarica, Y., Mavi, H. & Demirkiran, M. Bromocriptine is ineffective in the treatment of chronic nonfluent aphasia. Acta Neurol. Belg. 95, 235–238 (1995).

    CAS  PubMed  Google Scholar 

  112. Gupta, S. R., Mlcoch, A. G., Scolaro, C. & Moritz, T. Bromocriptine treatment of nonfluent aphasia. Neurology 45, 2170–2173 (1995).

    Article  CAS  PubMed  Google Scholar 

  113. Ashtary, F., Janghorbani, M., Chitsaz, A., Reisi, M. & Bahrami, A. A randomized, double blind trial of bromocriptine efficacy in nonfluent aphasia after stroke. Neurology 66, 914–916 (2006).

    Article  CAS  PubMed  Google Scholar 

  114. Bragoni, M. et al. Bromocriptine and speech therapy in non-fluent chronic aphasia after stroke. Neurol. Sci. 21, 19–22 (2000).

    Article  CAS  PubMed  Google Scholar 

  115. Walker-Batson, D. et al. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke 32, 2093–2098 (2001) .

    Article  CAS  PubMed  Google Scholar 

  116. Whiting, E., Chenery, H. J., Chalk, J. & Copland, D. A. Dexamphetamine boosts naming treatment effects in chronic aphasias. J. Int. Neuropsychol. Soc. 13, 972–979 (2007).

    Article  CAS  PubMed  Google Scholar 

  117. Beversdorf, D. Q. et al. Effect of propranolol on naming in chronic Broca's aphasia with anomia. Neurocase 13, 256–259 (2007).

    Article  PubMed  Google Scholar 

  118. Tanaka, Y. & Bachman, D. L. Pharmacotherapy of aphasia. In Neurobehavior of Language and Cognition: Studies of Normal Aging and Brain Damage (eds Connor, L. S. & Obler, L. K.) 159–162 (SpringerLink, Berlin, 2007).

    Google Scholar 

  119. Tsikunov, S. G. & Belokoskova, S. G. Psychophysiological analysis of the influence of vasopressin on speech in patients with post-stroke aphasias. Span. J. Psychol. 10, 178–188 (2007).

    Article  PubMed  Google Scholar 

  120. Ferris, S. et al. Treatment effects of memantine on language in moderate to severe Alzheimer's disease patients. Alzheimers Dement. 5, 375–379 (2009).

    Article  PubMed  Google Scholar 

  121. Román, G. C. et al. Randomized, placebo-controlled, clinical trial of donepezil in vascular dementia: differential affects by hippocampal size. Stroke 41, 1213–1221 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Berthier, M. L. et al. Open-label study of donepezil in post-stroke aphasia. Neurology 60, 1118–1119 (2003).

    Article  Google Scholar 

  123. Berthier, M. L., Moreno-Torres, I. & Hinojosa, J. Beneficial effects of donepezil and modality-specific language therapy on chronic conduction aphasia [abstract P06.014]. Neurology 62 (Suppl. 5), A462 (2004).

    Google Scholar 

  124. Berthier, M. L. et al. A randomized controlled trial of donepezil in poststroke aphasia. Neurology 67, 1687–1689 (2006).

    Article  CAS  PubMed  Google Scholar 

  125. Kavirajan, H. & Schneider, L. S. Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised controlled trials. Lancet Neurol. 6, 782–792 (2007).

    Article  CAS  PubMed  Google Scholar 

  126. Tanaka, Y., Miyazaki, M. & Albert, M. L. Effect of increased cholinergic activity on naming in aphasia. Lancet 350, 116–117 (1997).

    Article  CAS  PubMed  Google Scholar 

  127. Kabasawa, H. et al. Effects of bifemelane hydrochloride on cerebral circulation and metabolism in patients with aphasia. Clin. Ther. 16, 471–482 (1994).

    CAS  PubMed  Google Scholar 

  128. Jacobs, D. H. et al. Physostigmine pharmacotherapy for anomia. Neurocase 2, 83–91 (1996).

    Article  Google Scholar 

  129. Benke, T., Köylü, B., Delazer, M., Trinka, E. & Kemmler, G. Cholinergic treatment of amnesia following basal forebrain lesion due to aneurysm rupture—an open-label pilot study. Eur. J. Neurol. 12, 791–796 (2005).

    Article  CAS  PubMed  Google Scholar 

  130. Pashek, G. V. & Bachman, D. L. Cognitive, linguistic, and motor speech effects of donepezil hydrochloride in a patient with stroke-related aphasia and apraxia of speech. Brain Lang. 87, 179–180 (2003).

    Article  Google Scholar 

  131. Berthier, M. L. & Green, C. Donepezil improves speed and accuracy of information processing in chronic post-stroke aphasia [abstract P01.012]. Neurology 68 (Suppl. 1), A10 (2007).

    Google Scholar 

  132. Berthier, M. L. et al. Beneficial effect of donepezil on sensorimotor function after stroke. Am. J. Phys. Med. Rehabil. 82, 725–729 (2003).

    Google Scholar 

  133. Nadeau, S. E. 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).

    Article  PubMed  Google Scholar 

  134. Chen, Y. et al. The efficacy of donepezil for post-stroke aphasia: a pilot case control study. Zhonghua Nei Ke Za Zhi 49, 115–118 (2010).

    PubMed  Google Scholar 

  135. Martin, P. I. et al. Research with transcranial magnetic stimulation in the treatment of aphasia. Curr. Neurol. Neurosci. Rep. 9, 451–458 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Baker, J., Rorden, C. & Fridriksson, J. Using transcranial direct current stimulation (tDCS) to treat stroke patients with aphasia. Stroke 41, 1229–1236 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  137. Naeser, M. A. et al. Improved picture naming in chronic aphasia after TMS to part of right Broca's area: an open-protocol study. Brain Lang. 93, 95–105 (2005).

    Article  PubMed  Google Scholar 

  138. Winhuisen, L. et al. The right inferior frontal gyrus and poststroke aphasia: a follow-up investigation. Stroke 38, 1286–1292 (2007).

    Article  PubMed  Google Scholar 

  139. Winhuisen, L. et al. Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia: a combined repetitive transcranial magnetic stimulation and positron emission tomography study. Stroke 36, 1759–1763 (2005).

    Article  PubMed  Google Scholar 

  140. Floel, A., Rosser, N., Michka, O., Knecht, S. & Breitenstein, C. Noninvasive brain stimulation improves language learning. J. Cogn. Neurosci. 20, 1415–1422 (2008).

    Article  PubMed  Google Scholar 

  141. Liuzzi, G. et al. The involvement of the left motor cortex in learning of a novel action word lexicon. Curr. Biol. 20, 1745–1751 (2010).

    Article  CAS  PubMed  Google Scholar 

  142. Monti, A. et al. Improved naming after transcranial direct current stimulation in aphasia. J. Neurol. Neurosurg. Psychiatry 79, 451–453 (2008).

    Article  CAS  PubMed  Google Scholar 

  143. Miniussi, C. et al. Efficacy of repetitive transcranial magnetic stimulation/transcranial direct current stimulation in cognitive neurorehabilitation. Brain Stimul. 1, 326–336 (2008).

    Article  PubMed  Google Scholar 

  144. Crosson, B. et al. Role of the right and left hemispheres in recovery of function during treatment of intention in aphasia. J. Cogn. Neurosci. 17, 392–406 (2005).

    Article  PubMed  Google Scholar 

  145. Cherney, L. R. & Small, S. L. Task-dependent changes in brain activation following therapy for nonfluent aphasia: discussion of two individual cases. J. Int. Neuropsychol. Soc. 6, 828–842 (2006).

    Google Scholar 

  146. Fridriksson, J. et al. Neural correlates of phonological and semantic-based anomia treatment in aphasia. Neuropsychologia 45, 1812–1822 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  147. Raboyeau, G. et al. Right hemisphere activation in recovery from aphasia: lesion effect or function recruitment? Neurology 70, 290–298 (2008).

    Article  CAS  PubMed  Google Scholar 

  148. Menke, R. et al. Imaging short- and long-term training success in chronic aphasia. BMC Neurosci. 10, 118 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  149. Meinzer, M. et al. Integrity of the hippocampus and surrounding white matter is correlated with language training success in aphasia. Neuroimage 53, 283–290 (2010).

    Article  PubMed  Google Scholar 

  150. Price, C. J., Seghier, M. L. & Leff, A. P. Predicting language outcome and recovery after stroke: the PLORAS system. Nat. Rev. Neurol. 6, 202–210 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Saur, D. et al. Dynamics of language reorganization after stroke. Brain 129, 1371–1384 (2006).

    Article  PubMed  Google Scholar 

  152. Green Heredia, C., Sage, K., Lambon Ralph, M. A. & Berthier, M. L. Relearning and retention of verbal labels in a case of semantic dementia. Aphasiology 23, 192–209 (2009).

    Article  Google Scholar 

  153. Pulvermüller, F., Kherif, F., Hauk, O., Mohr, B. & Nimmo-Smith, I. Cortical cell assemblies for general lexical and category-specific semantic processing as revealed by fMRI cluster analysis. Hum. Brain Mapping 30, 3837–3850 (2009).

    Article  Google Scholar 

  154. Robbins, T. W. & Arnsten, A. F. The neuropsychopharmacology of fronto-executive function: monoaminergic modulation. Annu. Rev. Neurosci. 32, 267–287 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Sarter, M., Hasselmo, M. E., Bruno, J. P. & Givens, B. Unraveling the attentional functions of cortical cholinergic inputs: interactions between signal-driven and cognitive modulation of signal detection. Brain Res. Rev. 48, 98–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  156. Hasselmo, M. E. & McGaughy, J. High acetylcholine levels set circuit dynamics for attention and encoding and low acetylcholine levels set dynamics for consolidation. Prog. Brain Res. 145, 207–231 (2004).

    Article  CAS  PubMed  Google Scholar 

  157. Gotts, S. J., della Rocchetta, A. I. & Cipolotti, L. Mechanisms underlying perseveration in aphasia: evidence from a single case study. Neuropsychologia 40, 1930–1947 (2002).

    Article  PubMed  Google Scholar 

  158. Gauthier, L. V. et al. Remodeling the brain: plastic structural brain changes produced by different motor therapies after stroke. Stroke 39, 1520–1525 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The study was supported by the Ministerio de Educación y Ciencia, Spain (grant SEJ2007-67,793) and the Medical Research Council, UK (grants U1055.04.003.00001.01 and MC_US_A060_0034).

C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

Authors

Contributions

M. L. Berthier and F. Pulvermüller researched the data and wrote the article, and provided substantial contributions to discussions of the content, reviewing and editing of the manuscript.

Corresponding authors

Correspondence to Marcelo L. Berthier or Friedemann Pulvermüller.

Ethics declarations

Competing interests

M. L. Berthier has received honoraria from Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Merz, Novartis and Pfizer for consulting, and received honoraria from Janssen, Lundbeck, Merz and Pfizer for lectures. He has also received research funding from Eisai, Merz and Pfizer. F. Pulvermüller has received research funding from GlaxoSmithKline.

Supplementary information

Supplementary Table 1

Studies of constraint-induced aphasia therapy in poststroke aphasia (DOC 133 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berthier, M., Pulvermüller, F. Neuroscience insights improve neurorehabilitation of poststroke aphasia. Nat Rev Neurol 7, 86–97 (2011). https://doi.org/10.1038/nrneurol.2010.201

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2010.201

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing