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Is there a future for therapeutic use of transcranial magnetic stimulation?

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has in recent years been used to explore therapeutic opportunities in a bewildering variety of conditions. Although there is good evidence that this technique can modify cortical activity, the rationale for its use in many of the conditions investigated so far is not clear. Here we discuss the effects of rTMS in healthy subjects and how it has been used in a number of neurological conditions. We argue that a better understanding of both the effects of rTMS and the pathological processes underlying the conditions for which it is used will reveal whether rTMS really does offer therapeutic potential and, if so, for which conditions.

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Figure 1: Responses to single-pulse TMS.
Figure 2: How reptitive TMS affects excitablity in the brain.
Figure 3: Different repetitive TMS approaches.

References

  1. Macklis, R. M. Magnetic healing, quackery, and the debate about the health effects of electromagnetic fields. Ann. Intern. Med. 118, 376–383 (1993).

    CAS  PubMed  Google Scholar 

  2. Couturier, J. L. Efficacy of rapid-rate repetitive transcranial magnetic stimulation in the treatment of depression: a systematic review and meta-analysis. J. Psychiatry Neurosci. 30, 83–90 (2005).

    PubMed  PubMed Central  Google Scholar 

  3. Martin, J. L. et al. Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis. Br. J. Psychiatry 182, 480–491 (2003).

    PubMed  Google Scholar 

  4. Kozel, F. A. & George, M. S. Meta-analysis of left prefrontal repetitive transcranial magnetic stimulation (rTMS) to treat depression. J. Psychiatr. Pract. 8, 270–275 (2002).

    PubMed  Google Scholar 

  5. Mitchell, P. B. & Loo, C. K. Transcranial magnetic stimulation for depression. Aust. N. Z. J. Psychiatry 40, 406–413 (2006). One of the most recent meta-analyses examining the efficacy of rTMS for the treatment of depression. Concludes that although rTMS has a statistically significant effect on measures of depression the clinical significance is questionable.

    PubMed  Google Scholar 

  6. Burt, T., Lisanby, S. H. & Sackeim, H. A. Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int. J. Neuropsychopharmacol. 5, 73–103 (2002).

    PubMed  Google Scholar 

  7. Day, B. L. et al. Motor cortex stimulation in intact man. 2. Multiple descending volleys. Brain 110, 1191–1209 (1987). Describes the first recordings of multiple descending volleys evoked by TMS in humans. These findings provided insight into the mechanism by which TMS activates the cortex.

    PubMed  Google Scholar 

  8. Werhahn, K. J., Kunesch, E., Noachtar, S., Benecke, R. & Classen, J. Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J. Physiol. (Lond.) 517, 591–597 (1999).

    CAS  Google Scholar 

  9. Ziemann, U. Pharmacology of TMS. Suppl. Clin. Neurophysiol. 56, 226–231 (2003).

    PubMed  Google Scholar 

  10. Touge, T., Gerschlager, W., Brown, P. & Rothwell, J. C. Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses? Clin. Neurophysiol. 112, 2138–2145 (2001).

    CAS  PubMed  Google Scholar 

  11. Schlaghecken, F., Munchau, A., Bloem, B. R., Rothwell, J. & Eimer, M. Slow frequency repetitive transcranial magnetic stimulation affects reaction times, but not priming effects, in a masked prime task. Clin. Neurophysiol. 114, 1272–1277 (2003).

    CAS  PubMed  Google Scholar 

  12. Huang, Y. Z., Edwards, M. J., Rounis, E., Bhatia, K. P. & Rothwell, J. C. Theta burst stimulation of the human motor cortex. Neuron 45, 201–206 (2005).

    CAS  PubMed  Google Scholar 

  13. Lee, L. et al. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 5308–5318 (2003).

    CAS  PubMed  Google Scholar 

  14. Iyer, M. B., Schleper, N. & Wassermann, E. M. Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 10867–10872 (2003).

    CAS  PubMed  Google Scholar 

  15. Turrigiano, G. G. & Nelson, S. B. Homeostatic plasticity in the developing nervous system. Nature Rev. Neurosci. 5, 97–107 (2004).

    CAS  Google Scholar 

  16. Bienenstock, E. L., Cooper, L. N. & Munro, P. W. Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex. J. Neurosci. 2, 32–48 (1982).

    CAS  PubMed  Google Scholar 

  17. Stefan, K. et al. Temporary occlusion of associative motor cortical plasticity by prior dynamic motor training. Cereb. Cortex 16, 376–385 (2006). Described how prior motor training reduced the response to a subsequent facilitatory rTMS protocol. This seminal study provided evidence that rTMS influences circuits that are functionally important. It also provided indirect evidence that LTP-like changes are induced by such rTMS paradigms.

    PubMed  Google Scholar 

  18. Kuwabara, S., Cappelen-Smith, C., Lin, C. S., Mogyoros, I. & Burke, D. Effects of voluntary activity on the excitability of motor axons in the peroneal nerve. Muscle Nerve 25, 176–184 (2002).

    PubMed  Google Scholar 

  19. Stefan, K., Kunesch, E., Benecke, R., Cohen, L. G. & Classen, J. Mechanisms of enhancement of human motor cortex excitability induced by interventional paired associative stimulation. J. Physiol. (Lond.) 543, 699–708 (2002). Provided evidence that the lasting effects of rTMS protocols may be due to LTP-like mechanisms. Demonstrated that PAS effects are blocked by an NMDA-receptor antagonist.

    CAS  Google Scholar 

  20. Huang, Y. Z., Chen, R. S., Rothwell, J. C. & Wen, H. Y. The after-effect of human theta burst stimulation is NMDA receptor dependent. Clin. Neurophysiol. 118, 1028–1032 (2007).

    CAS  PubMed  Google Scholar 

  21. Hess, A. et al. Task-dependent modulation of inhibitory actions within the primary motor cortex. Exp. Brain Res. 124, 321–330 (1999).

    CAS  PubMed  Google Scholar 

  22. Hess, G. & Donoghue, J. P. Long-term potentiation of horizontal connections provides a mechanism to reorganize cortical motor maps. J. Neurophysiol. 71, 2543–2547 (1994).

    CAS  PubMed  Google Scholar 

  23. Levy, L. M., Ziemann, U., Chen, R. & Cohen, L. G. Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation. Ann. Neurol. 52, 755–761 (2002).

    CAS  PubMed  Google Scholar 

  24. Ziemann, U., Hallett, M. & Cohen, L. G. Mechanisms of deafferentation-induced plasticity in human motor cortex. J. Neurosci. 18, 7000–7007 (1998). Reports that temporary ischaemic block of the hand, which produces a reduction in GABA A inhibition in the contralateral motor cortex, facilitates the induction of plasticity by a low-frequency rTMS paradigm. By analogy with in vitro studies, this finding provides evidence that the effects of rTMS are due to an LTP-like mechanism.

    CAS  PubMed  Google Scholar 

  25. Neggers, S. F. et al. A stereotactic method for image-guided transcranial magnetic stimulation validated with fMRI and motor-evoked potentials. Neuroimage 21, 1805–1817 (2004).

    CAS  PubMed  Google Scholar 

  26. Stokes, M. G. et al. Simple metric for scaling motor threshold based on scalp–cortex distance: application to studies using transcranial magnetic stimulation. J. Neurophysiol. 94, 4520–4527 (2005).

    PubMed  Google Scholar 

  27. Stefan, K., Wycislo, M. & Classen, J. Modulation of associative human motor cortical plasticity by attention. J. Neurophysiol. 92, 66–72 (2004).

    PubMed  Google Scholar 

  28. Inghilleri, M. et al. Ovarian hormones and cortical excitability. An rTMS study in humans. Clin. Neurophysiol. 115, 1063–1068 (2004).

    CAS  PubMed  Google Scholar 

  29. Sale, M. V., Ridding, M. C. & Nordstrom, M. A. Factors influencing the magnitude and reproducibility of corticomotor excitability changes induced by paired associative stimulation. Exp. Brain Res. 9 May 2007 (doi:10.1007/500221-007-0960-x).

  30. Kleim, J. A. et al. BDNF val66met polymorphism is associated with modified experience-dependent plasticity in human motor cortex. Nature Neurosci. 9, 735–737 (2006). Describes how a val66met polymorphism in BDNF influences induction of plasticity by motor training. This is the first description of a genetic influence on induction of human cortical plasticity.

    CAS  PubMed  Google Scholar 

  31. Fregni, F. et al. Homeostatic effects of plasma valproate levels on corticospinal excitability changes induced by 1Hz rTMS in patients with juvenile myoclonic epilepsy. Clin. Neurophysiol. 117, 1217–1227 (2006).

    CAS  PubMed  Google Scholar 

  32. Rizzo, V. et al. Shaping the excitability of human motor cortex with premotor rTMS. J. Physiol. (Lond.) 554, 483–495 (2004).

    CAS  Google Scholar 

  33. Mir, P. et al. Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease. Neurology 14, 1906–1912 (2005).

    Google Scholar 

  34. Ziemann, U., Tam, A., Butefisch, C. & Cohen, L. G. Dual modulating effects of amphetamine on neuronal excitability and stimulation-induced plasticity in human motor cortex. Clin. Neurophysiol. 113, 1308–1315 (2002).

    CAS  PubMed  Google Scholar 

  35. Baumer, T. et al. Repeated premotor rTMS leads to cumulative plastic changes of motor cortex excitability in humans. Neuroimage 20, 550–560 (2003).

    PubMed  Google Scholar 

  36. Lefaucheur, J. P. New insights into the therapeutic potential of non-invasive transcranial cortical stimulation in chronic neuropathic pain. Pain 122, 11–13 (2006).

    PubMed  Google Scholar 

  37. Pascual-Leone, A., Rubio, B., Pallardo, F. & Catala, M. D. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 348, 233–237 (1996).

    CAS  PubMed  Google Scholar 

  38. George, M. S. et al. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport 6, 1853–1856 (1995). This paper is one of the earliest to describe the use of daily rTMS to treat the symptoms of depression.

    CAS  PubMed  Google Scholar 

  39. Cummings, J. L. The neuroanatomy of depression. J. Clin. Psychiatry 54, 14–20 (1993).

    PubMed  Google Scholar 

  40. Hirono, N. et al. Frontal lobe hypometabolism and depression in Alzheimer's disease. Neurology 50, 380–383 (1998).

    CAS  PubMed  Google Scholar 

  41. Klein, E. et al. Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Arch. Gen. Psychiatry 56, 315–320 (1999).

    CAS  PubMed  Google Scholar 

  42. Speer, A. M. et al. Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol. Psychiatry 48, 1133–1141 (2000).

    CAS  PubMed  Google Scholar 

  43. Miniussi, C. et al. Repetitive transcranial magnetic stimulation (rTMS) at high and low frequency: an efficacious therapy for major drug-resistant depression? Clin. Neurophysiol. 116, 1062–1071 (2005).

    CAS  PubMed  Google Scholar 

  44. Loo, C. et al. Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Am. J. Psychiatry 156, 946–948 (1999).

    CAS  PubMed  Google Scholar 

  45. Holtzheimer, P. E., Russo, J. & Avery, D. H. A meta-analysis of repetitive transcranial magnetic stimulation in the treatment of depression. Psychopharmacol. Bull. 35, 149–169 (2001).

    PubMed  Google Scholar 

  46. Lee, S. H. et al. A double blind study showing that two weeks of daily repetitive TMS over the left or right temporoparietal cortex reduces symptoms in patients with schizophrenia who are having treatment-refractory auditory hallucinations. Neurosci. Lett. 376, 177–181 (2005).

    CAS  PubMed  Google Scholar 

  47. Chibbaro, G. et al. Repetitive transcranial magnetic stimulation in schizophrenic patients reporting auditory hallucinations. Neurosci. Lett. 383, 54–57 (2005).

    CAS  PubMed  Google Scholar 

  48. Kleinjung, T. et al. Long-term effects of repetitive transcranial magnetic stimulation (rTMS) in patients with chronic tinnitus. Otolaryngol. Head Neck Surg. 132, 566–569 (2005).

    PubMed  Google Scholar 

  49. Langguth, B. et al. Neuronavigated rTMS in a patient with chronic tinnitus. Effects of 4 weeks treatment. Neuroreport 14, 977–980 (2003).

    PubMed  Google Scholar 

  50. Lee, R. G. & van Donkelaar, P. Mechanisms underlying functional recovery following stroke. Can. J. Neurol. Sci. 22, 257–263 (1995).

    CAS  PubMed  Google Scholar 

  51. Ward, N. S. & Frackowiak, R. S. The functional anatomy of cerebral reorganisation after focal brain injury. J. Physiol. (Paris) 99, 425–436 (2006).

    Google Scholar 

  52. Plautz, E. J. et al. Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: a feasibility study in primates. Neurol. Res. 25, 801–810 (2003).

    PubMed  Google Scholar 

  53. Brown, J. A., Lutsep, H. L., Weinand, M. & Cramer, S. C. Motor cortex stimulation for the enhancement of recovery from stroke: a prospective, multicenter safety study. Neurosurgery 58, 464–473 (2006).

    PubMed  Google Scholar 

  54. Khedr, E. M., Ahmed, M. A., Fathy, N. & Rothwell, J. C. Therapeutic trial of repetitive transcranial magnetic stimulation after acute ischemic stroke. Neurology 65, 466–468 (2005). Examined the possible facilitatory effect of rTMS applied in conjunction with conventional rehabilitative training. Demonstrated that 2 weeks' daily rTMS over the stroke-affected hemisphere increased the functional gain when compared with sham stimulation and therapy.

    PubMed  Google Scholar 

  55. Fregni, F. 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). A sham-controlled study examining the efficacy of an alternative approach for rehabilitation of stroke patients; namely the application of inhibitory rTMS over the unaffected motor cortical region

    PubMed  Google Scholar 

  56. Ziemann, U., Iliac, T. V., Pauli, C., Meintzschel, F. & Ruge, D. Learning modifies subsequent induction of long-term potentiation-like and long-term depression-like plasticity in human motor cortex. J. Neurosci. 24, 1666–1672 (2004).

    CAS  PubMed  Google Scholar 

  57. Roth, B. J., Saypol, J. M., Hallett, M. & Cohen, L. G. A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroencephalogr. Clin. Neurophysiol. 81, 47–56 (1991).

    CAS  PubMed  Google Scholar 

  58. Thielscher, A. & Kammer, T. Electric field properties of two commercial figure-8 coils in TMS: calculation of focality and efficiency. Clin. Neurophysiol. 115, 1697–1708 (2004).

    PubMed  Google Scholar 

  59. Stefan, K., Kunesch, E., Cohen, L. G., Benecke, R. & Classen, J. Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123, 572–584 (2000).

    PubMed  Google Scholar 

  60. Murase, N., Duque, J., Mazzocchio, R. & Cohen, L. G. Influence of interhemispheric interactions on motor function in chronic stroke. Ann. Neurol. 55, 400–409 (2004).

    PubMed  Google Scholar 

  61. Talelli, P., Greenwood, R. J. & Rothwell, J. C. Exploring theta burst stimulation as an intervention to improve motor recovery in chronic stroke. Clin. Neurophysiol. 118, 333–342 (2007).

    CAS  PubMed  Google Scholar 

  62. Takeuchi, N., Chuma, T., Matsuo, Y., Watanabe, I. & Ikoma, K. Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke 36, 2681–2686 (2005).

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  64. Pascual-Leone, A. et al. Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation. Neurology 44, 892–898 (1994).

    CAS  PubMed  Google Scholar 

  65. Koch, G. et al. rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease. Neurology 65, 623–625 (2005).

    CAS  PubMed  Google Scholar 

  66. Siebner, H. R. et al. Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer's cramp. Neurology 52, 529–537 (1999).

    CAS  PubMed  Google Scholar 

  67. Murase, N. et al. Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp. Brain 128, 104–115 (2005).

    PubMed  Google Scholar 

  68. Huang, Y. Z., Edwards, M. J., Bhatia, K. P. & Rothwell, J. C. One-Hz repetitive transcranial magnetic stimulation of the premotor cortex alters reciprocal inhibition in DYT1 dystonia. Mov. Disord. 19, 54–59 (2004).

    PubMed  Google Scholar 

  69. Khedr, E. M. et al. Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain. J. Neurol. Neurosurg. Psychiatry 76, 833–838 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Lefaucheur, J. P., Drouot, X., Keravel, Y. & Nguyen, J. P. Pain relief induced by repetitive transcranial magnetic stimulation of precentral cortex. Neuroreport 12, 2963–2965 (2001).

    CAS  PubMed  Google Scholar 

  71. Tergau, F., Naumann, U., Paulus, W. & Steinhoff, B. J. Low-frequency repetitive transcranial magnetic stimulation improves intractable epilepsy. Lancet 353, 2209 (1999).

    CAS  PubMed  Google Scholar 

  72. Menkes, D. L. & Gruenthal, M. Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia. Epilepsia 41, 240–242 (2000).

    CAS  PubMed  Google Scholar 

  73. Kinoshita, M. et al. Low-frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy — a pilot study. Seizure 14, 387–392 (2005).

    PubMed  Google Scholar 

  74. Menkes, D. L. & Gruenthal, M. Slow-frequency repetitive transcranial magnetic stimulation in a patient with focal cortical dysplasia. Epilepsia 41, 240–242 (2000).

    CAS  PubMed  Google Scholar 

  75. Di, Lazzaro, V. et al. Repetitive transcranial magnetic stimulation for ALS. A preliminary controlled study. Neurosci. Lett. 408, 135–140 (2006).

    Google Scholar 

  76. Camprodon, J. A., Martinez-Raga, J., Alonso-Alonso, M., Shih, M. C. & Pascual-Leone, A. One session of high frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex transiently reduces cocaine craving. Drug Alcohol Depend. 86, 91–94 (2007).

    PubMed  Google Scholar 

  77. Eichhammer, P. et al. High-frequency repetitive transcranial magnetic stimulation decreases cigarette smoking. J. Clin. Psychiatry 64, 951–953 (2003).

    PubMed  Google Scholar 

  78. Greenberg, B. D. et al. Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study. Am. J. Psychiatry 154, 867–869 (1997).

    CAS  PubMed  Google Scholar 

  79. Sachdev, P. S. et al. Right versus left prefrontal transcranial magnetic stimulation for obsessive-compulsive disorder: a preliminary investigation. J. Clin. Psychiatry 62, 981–984 (2001).

    CAS  PubMed  Google Scholar 

  80. Mantovani, A. et al. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS). Int. J. Neuropsychopharmacol. 9, 95–100 (2006).

    PubMed  Google Scholar 

  81. Sole-Padulles, C. et al. Repetitive transcranial magnetic stimulation effects on brain function and cognition among elders with memory dysfunction. A randomized sham-controlled study. Cereb. Cortex 16, 1487–1493 (2006).

    PubMed  Google Scholar 

  82. Siebner, H. R. et al. Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. Brain 126, 2710–2725 (2003).

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was funded by the Medical Research Council (UK), and the National Health and Medical Research Council (Australia).

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Correspondence to John C. Rothwell.

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Ridding, M., Rothwell, J. Is there a future for therapeutic use of transcranial magnetic stimulation?. Nat Rev Neurosci 8, 559–567 (2007). https://doi.org/10.1038/nrn2169

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