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Transcranial brain stimulation: potential and limitations

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e-Neuroforum

Abstract

The brain adapts to new requirements in response to activity, learning or reactions to environmental stimuli by continuous reorganization. These reorganization processes can be facilitated and augmented, or also inhibited and prevented, by transcranial neurostimulation. The most common methods are electrical or magnetic stimulation. However, few studies have dealt with the newer methods using near infrared or ultrasound stimulation.

Transcranial magnetic stimulation (TMS) allows the pain-free transfer of very short bursts of high intensity electrical energy through the skull and can induce action potentials. By varying the number and intensity of the stimuli, and the stimulus sequence, repetitive TMS (rTMS) can induce either inhibitory or facilitatory effects in the brain. A differentiation is made between short-lived interference with ongoing brain activity, and plastic changes that persist for a longer period beyond the end of the stimulation.

Weaker electric fields in the 1 mA range can be applied painlessly through the skull. These probably exert their effects by modulating neuronal membranes and influencing the spontaneous firing rate of cortical neurons. They encompass the range from transcranial direct current stimulation (tDCS) to high frequency alternating current stimulation (tACS) in the kilohertz range. In view of the multitude of physically possible stimulation algorithms, hypothesis-driven protocols based on cellular or neuronal network characteristics are particularly popular, in the effort to narrow the choices in a meaningful manner. Examples are theta burst stimulation or tACS in the so-called “ripple” frequency range. It is, of course, not possible to selectively stimulate individual neurons using transcranial stimulation techniques; however selective after-effects can be achieved when used in combination with neuropharmacologically active drugs. The use of these methods for neuroenhancement is now a topic of intense discussion.

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References

  1. Ali MM, Sellers KK, Frohlich F (2013) Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. J Neurosci 33:11262–11275

    Article  CAS  PubMed  Google Scholar 

  2. Antal A, Boros K, Poreisz C et al (2008) Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimul 1:97–105

    Article  PubMed  Google Scholar 

  3. Antal A, Kriener N, Lang N et al (2011) Cathodal transcranial direct current stimulation of the visual cortex in the prophylactic treatment of migraine. Cephalalgia 31:820–828

    Article  PubMed  Google Scholar 

  4. Antal A, Nitsche MA, Kruse W et al (2004) Direct current stimulation over V5 enhances visuomotor coordination by improving motion perception in humans. J Cogn Neurosci 16:521–527

    Article  PubMed  Google Scholar 

  5. Antal A, Terney D, Kuhnl S, Paulus W (2010) Anodal transcranial direct current stimulation of the motor cortex ameliorates chronic pain and reduces short intracortical inhibition. J Pain Symptom Manage 39:890–903

    Article  PubMed  Google Scholar 

  6. Antal A, Terney D, Poreisz C, Paulus W (2007) Towards unravelling task-related modulations of neuroplastic changes induced in the human motor cortex. Eur J Neurosci 26:2687–2691

    Article  PubMed  Google Scholar 

  7. Brittain JS, Probert-Smith P, Aziz TZ, Brown P (2013) Tremor suppression by rhythmic transcranial current stimulation. Curr Biol 23:436–440

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Brunoni AR, Zanao TA, Vanderhasselt MA et al (2014) Enhancement of affective processing induced by bifrontal transcranial direct current stimulation in patients with major depression. Neuromodulation 17:138–142

    Article  PubMed  Google Scholar 

  9. Cappelletti M, Gessaroli E, Hithersay R et al (2013) Transfer of cognitive training across magnitude dimensions achieved with concurrent brain stimulation of the parietal lobe. J Neurosci 33:14899–14907

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Coffman BA, Clark VP, Parasuraman R (2014) Battery powered thought: enhancement of attention, learning, and memory in healthy adults using transcranial direct current stimulation. NeuroImage 85 Pt 3:895–908

    Article  Google Scholar 

  11. Delvendahl I, Jung NH, Mainberger F et al (2010) Occlusion of bidirectional plasticity by preceding low-frequency stimulation in the human motor cortex. Clin Neurophysiol 121:594–602

    Article  PubMed  Google Scholar 

  12. Di Lazzaro V, Profice P, Pilato F et al (2010) The effects of motor cortex rTMS on corticospinal descending activity. Clin Neurophysiol 121:464–473

    Article  Google Scholar 

  13. Elias WJ, Huss D, Voss T et al (2013) A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med 369:640–648

    Article  CAS  PubMed  Google Scholar 

  14. Esser SK, Hill SL, Tononi G (2005) Modeling the effects of transcranial magnetic stimulation on cortical circuits. J Neurophysiol 94:622–639

    Article  CAS  PubMed  Google Scholar 

  15. Ferrucci R, Mameli F, Guidi I et al (2008) Transcranial direct current stimulation improves recognition memory in Alzheimer disease. Neurology 71:493–498

    Article  CAS  PubMed  Google Scholar 

  16. Fox PT, Narayana S, Tandon N et al (2004) Column-based model of electric field excitation of cerebral cortex. Hum Brain Mapp 22:1–14

    Article  PubMed  Google Scholar 

  17. Fritsch B, Reis J, Martinowich K et al (2010) Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66:198–204

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Gamboa OL, Antal A, Moliadze V, Paulus W (2010) Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation. Exp Brain Res 204:181–187 (Experimentelle Hirnforschung Experimentation cerebrale)

    Article  PubMed Central  PubMed  Google Scholar 

  19. Grapengiesser CJC (1801) Versuche den Galvanismus zur Heilungeiniger Krankheiten anzuwenden. Myliussische Buchhandlung, Berlin

  20. Grundey J, Thirugnanasambandam N, Kaminsky K et al (2012) Neuroplasticity in cigarette smokers is altered under withdrawal and partially restituted by nicotine exposition. J Neurosci 32:4156–4162

    Article  CAS  PubMed  Google Scholar 

  21. Guleyupoglu B, Schestatsky P, Edwards D et al (2013) Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations. J Neurosci Methods 219:297–311

    Article  PubMed  Google Scholar 

  22. Hamada M, Terao Y, Hanajima R et al (2008) Bidirectional long-term motor cortical plasticity and metaplasticity induced by quadripulse transcranial magnetic stimulation. J Physiol 586:3927–3947

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Helfrich RF, Schneider TR, Rach S et al (2014) Entrainment of brain oscillations by transcranial alternating current stimulation. Curr Biol 24:333–339

    Article  CAS  PubMed  Google Scholar 

  24. Hellwag CF, Jacobi M (1802) Erfahrungen über die Heilkräfte des Galvanismus und Betrachtungen über desselben chemische und physiologische Wirkungen. Friedrich Perthes, Hamburg

  25. Herwig U, Fallgatter AJ, Hoppner J et al (2007) Antidepressant effects of augmentative transcranial magnetic stimulation: randomised multicentre trial. Br J Psychiatry 191:441–448

    Article  CAS  PubMed  Google Scholar 

  26. Huang YZ, Edwards MJ, Rounis E et al (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206

    Article  CAS  PubMed  Google Scholar 

  27. Hummel F, Celnik P, Giraux P et al (2005) Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain 128:490–499

    Article  PubMed  Google Scholar 

  28. Ilic TV, Meintzschel F, Cleff U et al (2002) Short-interval paired-pulse inhibition and facilitation of human motor cortex: the dimension of stimulus intensity. J Physiol 545:153–167

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Kirson ED, Dbaly V, Tovarys F et al (2007) Alternating electric fields arrest cell proliferation in animal tumor models and human brain tumors. Proc Natl Acad Sci U S A 104:10152–10157

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Krieg TD, Salinas FS, Narayana S et al (2013) PET-based confirmation of orientation sensitivity of TMS-induced cortical activation in humans. Brain Stimul 6:898–904

    Article  PubMed  Google Scholar 

  31. Kujirai T, Caramia MD, Rothwell JC et al (1993) Corticocortical inhibition in human motor cortex. J Physiol (Lond) 471:501–519

  32. Kuo HI, Bikson M, Datta A et al (2013) Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study. Brain Stimul 6:644–648

    Article  PubMed  Google Scholar 

  33. Kuo MF, Paulus W, Nitsche MA (2008) Boosting focally-induced brain plasticity by dopamine. Cereb Cortex 18:648–651

    Article  PubMed  Google Scholar 

  34. Laczo B, Antal A, Niebergall R et al (2012) Transcranial alternating stimulation in a high gamma frequency range applied over V1 improves contrast perception but does not modulate spatial attention. Brain Stimul 5:484–491

    Article  PubMed  Google Scholar 

  35. Lang N, Siebner HR, Ward NS, Lee L, Nitsche MA, Paulus W, Rothwell JC, Lemon RN, Frackowiak RS (2005) How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain? European Journal of Neuroscience 22:495–504

    Article  PubMed Central  PubMed  Google Scholar 

  36. Lang N, Siebner HR, Ernst D et al (2004) Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects. Biol Psychiatry 56:634–639

    Article  PubMed  Google Scholar 

  37. Larson J, Wong D, Lynch G (1986) Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res 368:347–350

    Article  CAS  PubMed  Google Scholar 

  38. Legon W, Sato TF, Opitz A et al (2014) Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat Neurosci 17:322–329

    Article  CAS  PubMed  Google Scholar 

  39. Liebetanz D, Koch R, Mayenfels S et al (2009) Safety limits of cathodal transcranial direct current stimulation in rats. Clin Neurophysiol 120:1161–1167

    Article  PubMed  Google Scholar 

  40. Logothetis NK, Eschenko O, Murayama Y et al (2012) Hippocampal-cortical interaction during periods of subcortical silence. Nature 491:547–553

    Article  CAS  PubMed  Google Scholar 

  41. Logothetis NK, Kayser C, Oeltermann A (2007) In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation. Neuron 55:809–823

    Article  CAS  PubMed  Google Scholar 

  42. McCaig CD, Song B, Rajnicek AM (2009) Electrical dimensions in cell science. J Cell Sci 122:4267–4276

    Article  CAS  PubMed  Google Scholar 

  43. Merton PA, Morton HB (1980) Stimulation of the cerebral cortex in the intact human subject. Nature 285:227

    Article  CAS  PubMed  Google Scholar 

  44. Moliadze V, Antal A, Paulus W (2010) Boosting brain excitability by transcranial high frequency stimulation in the ripple range. J Physiol 588:4891–4904

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Moliadze V, Atalay D, Antal A, Paulus W (2012) Close to threshold transcranial electrical stimulation preferentially activates inhibitory networks before switching to excitation with higher intensities. Brain Stimul 5:505–511

    Article  PubMed  Google Scholar 

  46. Moliadze V, Zhao Y, Eysel U, Funke K (2003) Effect of transcranial magnetic stimulation on single-unit activity in the cat primary visual cortex. J Physiol 553:665–679

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Monte-Silva K, Kuo MF, Hessenthaler S et al (2013) Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation. Brain Stimul 6:424–432

    Article  PubMed  Google Scholar 

  48. Monte-Silva K, Kuo MF, Thirugnanasambandam N et al (2009) Dose-dependent inverted U-shaped effect of dopamine (D2-like) receptor activation on focal and nonfocal plasticity in humans. J Neurosci 29:6124–6131

    Article  CAS  PubMed  Google Scholar 

  49. Nitsche MA, Kuo MF, Karrasch R et al (2009) Serotonin affects transcranial direct current-induced neuroplasticity in humans. Biol Psychiatry 66:503–508

    Article  CAS  PubMed  Google Scholar 

  50. Nitsche MA, Paulus W (2000) Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol 527 Pt 3:633–639

    Article  Google Scholar 

  51. Nitsche MA, Schauenburg A, Lang N et al (2003) Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. J Cogn Neurosci15:619–626

    Google Scholar 

  52. O’Reardon JP, Solvason HB, Janicak PG et al (2007) Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 62:1208–1216

    Article  Google Scholar 

  53. Oliviero A, Mordillo-Mateos L, Arias P et al (2011) Transcranial static magnetic field stimulation (tSMS) of the human motor cortex. J Physiol 589:4949–4958

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Paulus W, Classen J, Cohen LG et al (2008) State of the art: pharmacologic effects on cortical excitability measures tested by transcranial magnetic stimulation. Brain Stimul 1:151–163

    Article  PubMed  Google Scholar 

  55. Paulus W, Peterchev AV, Ridding M (2013) Transcranial electric and magnetic stimulation: technique and paradigms. In: Lozano AM, Hallett M (eds) Handbook of Clinical Neurology, (3rd series), vol. 116 Brain Stimulation. Elsevier, Amsterdam, pp 330–342

  56. Polania R, Nitsche MA, Korman C et al (2012) The importance of timing in segregated theta phase-coupling for cognitive performance. Curr Biol 22:1314–1318

    Article  CAS  PubMed  Google Scholar 

  57. Polania R, Nitsche MA, Paulus W (2011) Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation. Hum Brain Mapp 32:1236–1249

    Article  PubMed  Google Scholar 

  58. Rahman A, Reato D, Arlotti M et al (2013) Cellular effects of acute direct current stimulation: somatic and synaptic terminal effects. J Physiol 591:2563–2578

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Reato D, Rahman A, Bikson M, Parra LC (2013) Effects of weak transcranial alternating current stimulation on brain activity-a review of known mechanisms from animal studies. Front Hum Neurosci 7:687

    Article  PubMed Central  PubMed  Google Scholar 

  60. Reis J, Schambra HM, Cohen LG et al (2009) Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc Natl Acad Sci U S A 106:1590–1595

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120:2008–2039

    Article  PubMed Central  PubMed  Google Scholar 

  62. Rothkegel H, Sommer M, Paulus W (2010) Breaks during 5 Hz rTMS are essential for facilitatory after effects. Clin Neurophysiol 121:426–430

    Article  CAS  PubMed  Google Scholar 

  63. Saiote C, Goldschmidt T, Timäus C et al (2014) Impact of transcranial direct current stimulation on fatigue in multiple sclerosis. Restor Neurol Neurosci (in press)

  64. Shirota Y, Hewitt M, Paulus W (2014) Neuroscientists do not use non-invasive brain stimulation on themselves for neural enhancement. Brain Stimul (in press)

  65. Siebner HR, Lang N, Rizzo V et al (2004) Preconditioning of low-frequency repetitive transcranial magnetic stimulation with transcranial direct current stimulation: evidence for homeostatic plasticity in the human motor cortex. J Neurosci 24:3379–3385

    Article  CAS  PubMed  Google Scholar 

  66. Sommer M, Norden C, Schmack L et al (2013) Opposite optimal current flow directions for induction of neuroplasticity and excitation threshold in the human motor cortex. Brain Stimul 6:363–370

    Article  PubMed  Google Scholar 

  67. Stefan K, Kunesch E, Cohen LG et al (2000) Induction of plasticity in the human motor cortex by paired associative stimulation. Brain 123 Pt 3:572–584

    Google Scholar 

  68. Terney D, Chaieb L, Moliadze V et al (2008) Increasing human brain excitability by transcranial high-frequency random noise stimulation. J Neurosci 28:14147–14155

    Article  CAS  PubMed  Google Scholar 

  69. Tufail Y, Matyushov A, Baldwin N et al (2010) Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66:681–694

    Article  CAS  PubMed  Google Scholar 

  70. Vlachos A, Muller-Dahlhaus F, Rosskopp J et al (2012) Repetitive magnetic stimulation induces functional and structural plasticity of excitatory postsynapses in mouse organotypic hippocampal slice cultures. J Neurosci 32:17514–17523

    Article  CAS  PubMed  Google Scholar 

  71. Voss U, Holzmann R, Hobson A et al (2014) Induction of self awareness in dreams through frontal low current stimulation of gamma activity. Nat Neurosci (in press)

  72. Wach C, Krause V, Moliadze V et al (2013) Effects of 10 Hz and 20 Hz transcranial alternating current stimulation (tACS) on motor functions and motor cortical excitability. Behav Brain Res 241:1–6

    Article  CAS  PubMed  Google Scholar 

  73. Zaehle T, Herrmann CS (2011) Neural synchrony and white matter variations in the human brain—Relation between evoked gamma frequency and corpus callosum morphology. Int J Psychophysiol 79:49–54

    Article  PubMed  Google Scholar 

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Conflict of interest. W. Paulus states that he is a member of the scientific advisory board of EBS Technologies. The accompanying manuscript does not include studies on humans or animals.

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Paulus, W. Transcranial brain stimulation: potential and limitations. e-Neuroforum 5, 29–36 (2014). https://doi.org/10.1007/s13295-014-0056-6

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