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Studying and modifying brain function with non-invasive brain stimulation

Nature Neuroscience volume 21, pages 174–187 (2018)Cite this article

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Abstract

In the past three decades, our understanding of brain–behavior relationships has been significantly shaped by research using non-invasive brain stimulation (NIBS) techniques. These methods allow non-invasive and safe modulation of neural processes in the healthy brain, enabling researchers to directly study how experimentally altered neural activity causally affects behavior. This unique property of NIBS methods has, on the one hand, led to groundbreaking findings on the brain basis of various aspects of behavior and has raised interest in possible clinical and practical applications of these methods. On the other hand, it has also triggered increasingly critical debates about the properties and possible limitations of these methods. In this review, we discuss these issues, clarify the challenges associated with the use of currently available NIBS techniques for basic research and practical applications, and provide recommendations for studies using NIBS techniques to establish brain–behavior relationships.

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Fig. 1: Overview of NIBS methods.
Fig. 2: Examples of NIBS methods to study brain–function relationships.
Fig. 3: Example factors determining the variability of neurophysiological and behavioral NIBS effects.
Fig. 4: The conclusiveness of NIBS results on brain–behavior relations depends on the degree of methodological effort.
Fig. 5: Example workflows of studies employing NIBS methods in a multimethods approach to establish brain–behavior relations.
Fig. 6: Methodical considerations during different stages of NIBS experiments. 
Box Fig. 1: Spatial focality of NIBS methods estimated by electric field (EF) models.

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References

  1. Katz, L. N., Yates, J. L., Pillow, J. W. & Huk, A. C. Dissociated functional significance of decision-related activity in the primate dorsal stream. Nature 535, 285–288 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lomber, S. G., Payne, B. R. & Horel, J. A. The cryoloop: an adaptable reversible cooling deactivation method for behavioral or electrophysiological assessment of neural function. J. Neurosci. Methods 86, 179–194 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Tehovnik, E. J., Tolias, A. S., Sultan, F., Slocum, W. M. & Logothetis, N. K. Direct and indirect activation of cortical neurons by electrical microstimulation. J. Neurophysiol. 96, 512–521 (2006).

    Article  CAS  PubMed  Google Scholar 

  4. Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389–412 (2011).

    Article  CAS  PubMed  Google Scholar 

  5. Merton, P. A. & Morton, H. B. Stimulation of the cerebral cortex in the intact human subject. Nature 285, 227 (1980).

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  7. Poreisz, C., Boros, K., Antal, A. & Paulus, W. Safety aspects of transcranial direct current stimulation concerning healthy subjects and patients. Brain Res. Bull. 72, 208–214 (2007).

    Article  PubMed  Google Scholar 

  8. Kar, K. & Krekelberg, B. Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin. J. Neurophysiol. 108, 2173–2178 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Kar, K., Duijnhouwer, J. & Krekelberg, B. Transcranial alternating current stimulation attenuates neuronal adaptation. J. Neurosci. 37, 2325–2335 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hallett, M. Transcranial magnetic stimulation: a primer. Neuron 55, 187–199 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Amassian, V. E. et al. Suppression of visual perception by magnetic coil stimulation of human occipital cortex. Electroencephalogr. Clin. Neurophysiol. 74, 458–462 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. Pascual-Leone, A., Gates, J. R. & Dhuna, A. Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation. Neurology 41, 697–702 (1991).

    Article  CAS  PubMed  Google Scholar 

  13. Koch, G. & Rothwell, J. C. TMS investigations into the task-dependent functional interplay between human posterior parietal and motor cortex. Behav. Brain Res. 202, 147–152 (2009).

    Article  PubMed  Google Scholar 

  14. Feredoes, E., Heinen, K., Weiskopf, N., Ruff, C. & Driver, J. Causal evidence for frontal involvement in memory target maintenance by posterior brain areas during distracter interference of visual working memory. Proc. Natl. Acad. Sci. USA 108, 17510–17515 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Blankenburg, F. et al. Studying the role of human parietal cortex in visuospatial attention with concurrent TMS-fMRI. Cereb. Cortex 20, 2702–2711 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Romei, V., Driver, J., Schyns, P. G. & Thut, G. Rhythmic TMS over parietal cortex links distinct brain frequencies to global versus local visual processing. Curr. Biol. 21, 334–337 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hanslmayr, S., Matuschek, J. & Fellner, M.-C. Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation. Curr. Biol. 24, 904–909 (2014).

    Article  CAS  PubMed  Google Scholar 

  18. Albouy, P., Weiss, A., Baillet, S. & Zatorre, R. J. Selective entrainment of theta oscillations in the dorsal stream causally enhances auditory working memory performance. Neuron 94, 193–206.e5 (2017).

    Article  CAS  PubMed  Google Scholar 

  19. Nitsche, M. A., Müller-Dahlhaus, F., Paulus, W. & Ziemann, U. The pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugs. J. Physiol. (Lond.) 590, 4641–4662 (2012).

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. 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).

    Article  CAS  PubMed  Google Scholar 

  22. Ueyama, E. et al. Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats. Psychiatry Clin. Neurosci 65, 77–81 (2011).

    Article  PubMed  Google Scholar 

  23. Silvanto, J., Muggleton, N. & Walsh, V. State-dependency in brain stimulation studies of perception and cognition. Trends Cogn. Sci. 12, 447–454 (2008).

    Article  PubMed  Google Scholar 

  24. Gerloff, C., Corwell, B., Chen, R., Hallett, M. & Cohen, L. G. Stimulation over the human supplementary motor area interferes with the organization of future elements in complex motor sequences. Brain 120, 1587–1602 (1997).

    Article  PubMed  Google Scholar 

  25. Day, B. L. et al. Delay in the execution of voluntary movement by electrical or magnetic brain stimulation in intact man. Evidence for the storage of motor programs in the brain. Brain 112, 649–663 (1989).

    Article  PubMed  Google Scholar 

  26. Pascual-Leone, A. & Walsh, V. Fast backprojections from the motion to the primary visual area necessary for visual awareness. Science 292, 510–512 (2001).

    Article  CAS  PubMed  Google Scholar 

  27. Hallett, M. Plasticity of the human motor cortex and recovery from stroke. Brain Res. Brain Res. Rev. 36, 169–174 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Chen, R., Cohen, L. G. & Hallett, M. Nervous system reorganization following injury. Neuroscience 111, 761–773 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Amedi, A., Floel, A., Knecht, S., Zohary, E. & Cohen, L. G. Transcranial magnetic stimulation of the occipital pole interferes with verbal processing in blind subjects. Nat. Neurosci. 7, 1266–1270 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Nitsche, M. A. et al. Level of action of cathodal DC polarisation induced inhibition of the human motor cortex. Clin. Neurophysiol. 114, 600–604 (2003).

    Article  PubMed  Google Scholar 

  31. Nitsche, M. A. & Paulus, W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J. Physiol. (Lond.) 527, 633–639 (2000).

    Article  CAS  Google Scholar 

  32. Nitsche, M. A. et al. Pharmacological modulation of cortical excitability shifts induced by transcranial direct current stimulation in humans. J. Physiol. (Lond.) 553, 293–301 (2003).

    Article  CAS  Google Scholar 

  33. Nitsche, M. A. & Paulus, W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57, 1899–1901 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Bolzoni, F., Pettersson, L.-G. & Jankowska, E. Evidence for long-lasting subcortical facilitation by transcranial direct current stimulation in the cat. J. Physiol. (Lond.) 591, 3381–3399 (2013).

    Article  CAS  Google Scholar 

  35. Polanía, R., Paulus, W. & Nitsche, M. A. Modulating cortico-striatal and thalamo-cortical functional connectivity with transcranial direct current stimulation. Hum. Brain Mapp. 33, 2499–2508 (2012).

    Article  PubMed  Google Scholar 

  36. Kuo, H.-I. et al. Comparing cortical plasticity induced by conventional and high-definition 4 × 1 ring tDCS: a neurophysiological study. Brain Stimul. 6, 644–648 (2013).

    Article  PubMed  Google Scholar 

  37. Siegel, M., Donner, T. H. & Engel, A. K. Spectral fingerprints of large-scale neuronal interactions. Nat. Rev. Neurosci. 13, 121–134 (2012).

    Article  CAS  PubMed  Google Scholar 

  38. Antal, A. & Paulus, W. Transcranial alternating current stimulation (tACS). Front. Hum. Neurosci. 7, 317 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  39. Ali, M. M., Sellers, K. K. & Fröhlich, F. Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. J. Neurosci. 33, 11262–11275 (2013).

    Article  CAS  PubMed  Google Scholar 

  40. Ozen, S. et al. Transcranial electric stimulation entrains cortical neuronal populations in rats. J. Neurosci. 30, 11476–11485 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Joundi, R. A., Jenkinson, N., Brittain, J.-S., Aziz, T. Z. & Brown, P. Driving oscillatory activity in the human cortex enhances motor performance. Curr. Biol. 22, 403–407 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Cecere, R., Rees, G. & Romei, V. Individual differences in alpha frequency drive crossmodal illusory perception. Curr. Biol. 25, 231–235 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Moisa, M., Polania, R., Grueschow, M. & Ruff, C. C. Brain network mechanisms underlying motor enhancement by transcranial entrainment of gamma oscillations. J. Neurosci. 36, 12053–12065 (2016).

    Article  CAS  PubMed  Google Scholar 

  44. Minami, S. & Amano, K. Illusory jitter perceived at the frequency of alpha oscillations. Curr. Biol. 27, 2344–2351.e4 (2017).

    Article  CAS  PubMed  Google Scholar 

  45. Alekseichuk, I., Turi, Z., Amador de Lara, G., Antal, A. & Paulus, W. Spatial working memory in humans depends on theta and high gamma synchronization in the prefrontal cortex. Curr. Biol. 26, 1513–1521 (2016).

    Article  CAS  PubMed  Google Scholar 

  46. Santarnecchi, E. et al. Frequency-dependent enhancement of fluid intelligence induced by transcranial oscillatory potentials. Curr. Biol. 23, 1449–1453 (2013).

    Article  CAS  PubMed  Google Scholar 

  47. Polanía, R., Nitsche, M. A., Korman, C., Batsikadze, G. & Paulus, W. The importance of timing in segregated theta phase-coupling for cognitive performance. Curr. Biol. 22, 1314–1318 (2012).

    Article  PubMed  CAS  Google Scholar 

  48. Polanía, R., Moisa, M., Opitz, A., Grueschow, M. & Ruff, C. C. The precision of value-based choices depends causally on fronto-parietal phase coupling. Nat. Commun. 6, 8090 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Violante, I. R. et al. Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance. Elife 6, 91–95 (2017).

    Article  Google Scholar 

  50. Bächinger, M. et al. Concurrent tACS-fMRI reveals causal influence of power synchronized neural activity on resting state fMRI connectivity. J. Neurosci. 37, 4766–4777 (2017).

    Article  PubMed  Google Scholar 

  51. Romei, V., Gross, J. & Thut, G. Sounds reset rhythms of visual cortex and corresponding human visual perception. Curr. Biol. 22, 807–813 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Berényi, A., Belluscio, M., Mao, D. & Buzsáki, G. Closed-loop control of epilepsy by transcranial electrical stimulation. Science 337, 735–737 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Ngo, H.-V. V., Martinetz, T., Born, J. & Mölle, M. Auditory closed-loop stimulation of the sleep slow oscillation enhances memory. Neuron 78, 545–553 (2013).

    Article  CAS  PubMed  Google Scholar 

  54. Lustenberger, C. et al. Feedback-controlled transcranial alternating current stimulation reveals a functional role of sleep spindles in motor memory consolidation. Curr. Biol. 26, 2127–2136 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Roth, Y., Zangen, A. & Hallett, M. A coil design for transcranial magnetic stimulation of deep brain regions. J. Clin. Neurophysiol. 19, 361–370 (2002).

    Article  PubMed  Google Scholar 

  56. Roth, Y., Amir, A., Levkovitz, Y. & Zangen, A. Three-dimensional distribution of the electric field induced in the brain by transcranial magnetic stimulation using figure-8 and deep H-coils. J. Clin. Neurophysiol. 24, 31–38 (2007).

    Article  PubMed  Google Scholar 

  57. Grossman, N. et al. Noninvasive deep brain stimulation via temporally interfering electric Fields. Cell 169, 1029–1041.e16 (2017).

    Article  CAS  PubMed  Google Scholar 

  58. Noury, N. & Siegel, M. Phase properties of transcranial electrical stimulation artifacts in electrophysiological recordings. Neuroimage 158, 406–416 (2017).

    Article  PubMed  Google Scholar 

  59. Noury, N., Hipp, J. F. & Siegel, M. Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation. Neuroimage 140, 99–109 (2016).

    Article  PubMed  Google Scholar 

  60. Terney, D., Chaieb, L., Moliadze, V., Antal, A. & Paulus, W. Increasing human brain excitability by transcranial high-frequency random noise stimulation. J. Neurosci. 28, 14147–14155 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Fertonani, A., Pirulli, C. & Miniussi, C. Random noise stimulation improves neuroplasticity in perceptual learning. J. Neurosci. 31, 15416–15423 (2011).

    Article  CAS  PubMed  Google Scholar 

  62. Saiote, C., Polanía, R., Rosenberger, K., Paulus, W. & Antal, A. High-frequency TRNS reduces BOLD activity during visuomotor learning. PLoS One 8, e59669 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. van der Groen, O. & Wenderoth, N. Transcranial random noise stimulation of visual cortex: stochastic resonance enhances central mechanisms of perception. J. Neurosci. 36, 5289–5298 (2016).

    Article  PubMed  CAS  Google Scholar 

  64. Miniussi, C., Harris, J. A. & Ruzzoli, M. Modelling non-invasive brain stimulation in cognitive neuroscience. Neurosci. Biobehav. Rev. 37, 1702–1712 (2013).

    Article  PubMed  Google Scholar 

  65. Silvanto, J., Cowey, A., Lavie, N. & Walsh, V. Striate cortex (V1) activity gates awareness of motion. Nat. Neurosci. 8, 143–144 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Plewnia, C. et al. Dose-dependent attenuation of auditory phantom perception (tinnitus) by PET-guided repetitive transcranial magnetic stimulation. Hum. Brain Mapp. 28, 238–246 (2007).

    Article  PubMed  Google Scholar 

  67. Muellbacher, W. et al. Early consolidation in human primary motor cortex. Nature 415, 640–644 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Polanía, R., Nitsche, M. A. & Paulus, W. Modulating functional connectivity patterns and topological functional organization of the human brain with transcranial direct current stimulation. Hum. Brain Mapp. 32, 1236–1249 (2011).

    Article  PubMed  Google Scholar 

  69. Reis, J. et al. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. Proc. Natl. Acad. Sci. USA 106, 1590–1595 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Bolognini, N., Rossetti, A., Maravita, A. & Miniussi, C. Seeing touch in the somatosensory cortex: a TMS study of the visual perception of touch. Hum. Brain Mapp. 32, 2104–2114 (2011).

    Article  PubMed  Google Scholar 

  71. Tarapore, P. E. et al. Language mapping with navigated repetitive TMS: proof of technique and validation. Neuroimage 82, 260–272 (2013).

    Article  PubMed  Google Scholar 

  72. Holland, R. et al. Speech facilitation by left inferior frontal cortex stimulation. Curr. Biol. 21, 1403–1407 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Sparing, R. et al. Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. Brain 132, 3011–3020 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Ashbridge, E., Walsh, V. & Cowey, A. Temporal aspects of visual search studied by transcranial magnetic stimulation. Neuropsychologia 35, 1121–1131 (1997).

    Article  CAS  PubMed  Google Scholar 

  75. Oliveri, M. et al. Parieto-frontal interactions in visual-object and visual-spatial working memory: evidence from transcranial magnetic stimulation. Cereb. Cortex 11, 606–618 (2001).

    Article  CAS  PubMed  Google Scholar 

  76. Wang, J. X. et al. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science 345, 1054–1057 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cohen Kadosh, R., Soskic, S., Iuculano, T., Kanai, R. & Walsh, V. Modulating neuronal activity produces specific and long-lasting changes in numerical competence. Curr. Biol. 20, 2016–2020 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Philiastides, M. G., Auksztulewicz, R., Heekeren, H. R. & Blankenburg, F. Causal role of dorsolateral prefrontal cortex in human perceptual decision making. Curr. Biol. 21, 980–983 (2011).

    Article  CAS  PubMed  Google Scholar 

  79. Raja Beharelle, A., Polanía, R., Hare, T. A. & Ruff, C. C. Transcranial stimulation over frontopolar cortex elucidates the choice attributes and neural mechanisms used to resolve exploration-exploitation trade-offs. J. Neurosci. 35, 14544–14556 (2015).

    Article  PubMed  CAS  Google Scholar 

  80. Maréchal, M. A., Cohn, A., Ugazio, G. & Ruff, C. C. Increasing honesty in humans with noninvasive brain stimulation. Proc. Natl. Acad. Sci. USA 114, 4360–4364 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Strang, S. et al. Be nice if you have to—the neurobiological roots of strategic fairness. Soc. Cogn. Affect. Neurosci. 10, 790–796 (2015).

    Article  PubMed  Google Scholar 

  82. Ruff, C. C., Ugazio, G. & Fehr, E. Changing social norm compliance with noninvasive brain stimulation. Science 342, 482–484 (2013).

    Article  CAS  PubMed  Google Scholar 

  83. Knoch, D., Pascual-Leone, A., Meyer, K., Treyer, V. & Fehr, E. Diminishing reciprocal fairness by disrupting the right prefrontal cortex. Science 314, 829–832 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Pashler, H. & Wagenmakers, E.-J. Editors’ introduction to the special section on replicability in psychological science: a crisis of confidence? Perspect. Psychol. Sci. 7, 528–530 (2012).

    Article  PubMed  Google Scholar 

  85. Eklund, A., Nichols, T. E. & Knutsson, H. Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates. Proc. Natl. Acad. Sci. USA 113, 7900–7905 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Du, X., Summerfelt, A., Chiappelli, J., Holcomb, H. H. & Hong, L. E. Individualized brain inhibition and excitation profile in response to paired-pulse TMS. J. Mot. Behav. 46, 39–48 (2014).

    Article  PubMed  Google Scholar 

  87. Rioult-Pedotti, M. S., Friedman, D. & Donoghue, J. P. Learning-induced LTP in neocortex. Science 290, 533–536 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Wiethoff, S., Hamada, M. & Rothwell, J. C. Variability in response to transcranial direct current stimulation of the motor cortex. Brain Stimul. 7, 468–475 (2014).

    Article  PubMed  Google Scholar 

  89. Strube, W. et al. Bidirectional variability in motor cortex excitability modulation following 1 mA transcranial direct current stimulation in healthy participants. Physiol. Rep. 4, e12884 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  90. López-Alonso, V., Cheeran, B., Río-Rodríguez, D. & Fernández-Del-Olmo, M. Inter-individual variability in response to non-invasive brain stimulation paradigms. Brain Stimul. 7, 372–380 (2014).

    Article  PubMed  Google Scholar 

  91. Horvath, J. C., Forte, J. D. & Carter, O. Quantitative review finds no evidence of cognitive effects in healthy populations from single-session transcranial direct current stimulation (tDCS). Brain Stimul. 8, 535–550 (2015).

    Article  PubMed  Google Scholar 

  92. Horvath, J. C., Forte, J. D. & Carter, O. Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: a systematic review. Neuropsychologia 66, 213–236 (2015).

    Article  PubMed  Google Scholar 

  93. Nitsche, M. A., Bikson, M. & Bestmann, S. On the use of meta-analysis in neuromodulatory non-invasive brain stimulation. Brain Stimul. 8, 666–667 (2015).

    Article  PubMed  Google Scholar 

  94. Antal, A., Keeser, D., Priori, A., Padberg, F. & Nitsche, M. A. Conceptual and procedural shortcomings of the systematic review “Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human subjects: a systematic review” by Horvath and co-workers. Brain Stimul. 8, 846–849 (2015).

    Article  CAS  PubMed  Google Scholar 

  95. Ridding, M. C. & Ziemann, U. Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects. J. Physiol. (Lond.) 588, 2291–2304 (2010).

    Article  CAS  Google Scholar 

  96. Chaieb, L., Antal, A., Ambrus, G. G. & Paulus, W. Brain-derived neurotrophic factor: its impact upon neuroplasticity and neuroplasticity inducing transcranial brain stimulation protocols. Neurogenetics 15, 1–11 (2014).

    Article  CAS  PubMed  Google Scholar 

  97. Monte-Silva, K. et al. D2 receptor block abolishes θ burst stimulation-induced neuroplasticity in the human motor cortex. Neuropsychopharmacology 36, 2097–2102 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Fresnoza, S., Paulus, W., Nitsche, M. A. & Kuo, M.-F. Nonlinear dose-dependent impact of D1 receptor activation on motor cortex plasticity in humans. J. Neurosci. 34, 2744–2753 (2014).

    Article  CAS  PubMed  Google Scholar 

  99. Nitsche, M. A. et al. Dopaminergic modulation of long-lasting direct current-induced cortical excitability changes in the human motor cortex. Eur. J. Neurosci 23, 1651–1657 (2006).

    Article  PubMed  Google Scholar 

  100. Gentner, R., Wankerl, K., Reinsberger, C., Zeller, D. & Classen, J. Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity. Cereb. Cortex 18, 2046–2053 (2008).

    Article  PubMed  Google Scholar 

  101. Batsikadze, G., Moliadze, V., Paulus, W., Kuo, M.-F. & Nitsche, M. A. Partially non-linear stimulation intensity-dependent effects of direct current stimulation on motor cortex excitability in humans. J. Physiol. (Lond.) 591, 1987–2000 (2013).

    Article  CAS  Google Scholar 

  102. Thirugnanasambandam, N. et al. Isometric contraction interferes with transcranial direct current stimulation (tDCS) induced plasticity: evidence of state-dependent neuromodulation in human motor cortex. Restor. Neurol. Neurosci. 29, 311–320 (2011).

    PubMed  Google Scholar 

  103. Woods, A. J. et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin. Neurophysiol. 127, 1031–1048 (2016).

    Article  CAS  PubMed  Google Scholar 

  104. Schmidt, F.L. & Hunter, J.E. Methods of Meta-analysis: Correcting Error and Bias in Research Findings (Sage, Thousand Oaks, CA, USA, 2014).

  105. Parazzini, M. et al. A computational model of the electric field distribution due to regional personalized or nonpersonalized electrodes to select transcranial electric stimulation target. IEEE Trans. Biomed. Eng. 64, 184–195 (2017).

    Article  PubMed  Google Scholar 

  106. Opitz, A. et al. Physiological observations validate finite element models for estimating subject-specific electric field distributions induced by transcranial magnetic stimulation of the human motor cortex. Neuroimage 81, 253–264 (2013).

    Article  PubMed  Google Scholar 

  107. Gamboa, O. L., Antal, A., Moliadze, V. & Paulus, W. Simply longer is not better: reversal of theta burst after-effect with prolonged stimulation. Exp. Brain Res. 204, 181–187 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Lin, C.-H. et al. Age related differences in the neural substrates of motor sequence learning after interleaved and repetitive practice. Neuroimage 62, 2007–2020 (2012).

    Article  PubMed  Google Scholar 

  109. Pascual-Leone, A., Valls-Solé, J., Wassermann, E. M. & Hallett, M. Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. Brain 117, 847–858 (1994).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  111. Saturnino, G. B., Madsen, K. H., Siebner, H. R. & Thielscher, A. How to target inter-regional phase synchronization with dual-site transcranial alternating current stimulation. Neuroimage 163, 68–80 (2017).

    Article  PubMed  Google Scholar 

  112. Wurzman, R., Hamilton, R. H., Pascual-Leone, A. & Fox, M. D. An open letter concerning do-it-yourself users of transcranial direct current stimulation. Ann. Neurol. 80, 1–4 (2016).

    Article  PubMed  Google Scholar 

  113. Cohen Kadosh, R., Levy, N., O’Shea, J., Shea, N. & Savulescu, J. The neuroethics of non-invasive brain stimulation. Curr. Biol. 22, R108–R111 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Reardon, S. ‘Brain doping’ may improve athletes’ performance. Nature 531, 283–284 (2016).

    Article  CAS  PubMed  Google Scholar 

  115. Cabrera, L. Y., Evans, E. L. & Hamilton, R. H. Ethics of the electrified mind: defining issues and perspectives on the principled use of brain stimulation in medical research and clinical care. Brain Topogr. 27, 33–45 (2014).

    Article  PubMed  Google Scholar 

  116. Fitz, N. S. & Reiner, P. B. The challenge of crafting policy for do-it-yourself brain stimulation. J. Med. Ethics 41, 410–412 (2015).

    Article  PubMed  Google Scholar 

  117. Hill, C. A. et al. A causal account of the brain network computations underlying strategic social behavior. Nat. Neurosci. 20, 1142–1149 (2017).

    Article  CAS  PubMed  Google Scholar 

  118. Rose, N. S. et al. Reactivation of latent working memories with transcranial magnetic stimulation. Science 354, 1136–1139 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Barron, H. C. et al. Unmasking latent inhibitory connections in human cortex to reveal dormant cortical memories. Neuron 90, 191–203 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Thut, G. et al. Rhythmic TMS causes local entrainment of natural oscillatory signatures. Curr. Biol. 21, 1176–1185 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  122. Stagg, C. J., Bachtiar, V. & Johansen-Berg, H. The role of GABA in human motor learning. Curr. Biol. 21, 480–484 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Stagg, C. J. et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J. Neurosci. 29, 5202–5206 (2009).

    Article  CAS  PubMed  Google Scholar 

  124. Trepel, C. & Racine, R. J. GABAergic modulation of neocortical long-term potentiation in the freely moving rat. Synapse 35, 120–128 (2000).

    Article  CAS  PubMed  Google Scholar 

  125. Open Science Collaboration. Estimating the reproducibility of psychological science. Science 349, aac4716 (2015).

    Article  CAS  Google Scholar 

  126. Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 14, 365–376 (2013).

    Article  CAS  PubMed  Google Scholar 

  127. Simonsohn, U., Nelson, L. D. & Simmons, J. P. p-Curve and effect size: correcting for publication bias using only significant results. Perspect. Psychol. Sci. 9, 666–681 (2014).

    Article  PubMed  Google Scholar 

  128. Morbidi, F. et al. Off-line removal of TMS-induced artifacts on human electroencephalography by Kalman filter. J. Neurosci. Methods 162, 293–302 (2007).

    Article  PubMed  Google Scholar 

  129. Gandiga, P. C., Hummel, F. C. & Cohen, L. G. Transcranial DC stimulation (tDCS): a tool for double-blind sham-controlled clinical studies in brain stimulation. Clin. Neurophysiol. 117, 845–850 (2006).

    Article  PubMed  Google Scholar 

  130. Kanai, R., Chaieb, L., Antal, A., Walsh, V. & Paulus, W. Frequency-dependent electrical stimulation of the visual cortex. Curr. Biol. 18, 1839–1843 (2008).

    Article  CAS  PubMed  Google Scholar 

  131. Fostering reproducible fMRI research. Nat. Commun. 8, 14748 (2017).

    Article  CAS  Google Scholar 

  132. Chipchase, L. et al. A checklist for assessing the methodological quality of studies using transcranial magnetic stimulation to study the motor system: an international consensus study. Clin. Neurophysiol. 123, 1698–1704 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Buch, E. R. et al. Effects of tDCS on motor learning and memory formation: A consensus and critical position paper. Clin. Neurophysiol. 128, 589–603 (2017).

    Article  PubMed  Google Scholar 

  134. Lefaucheur, J.-P. et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin. Neurophysiol. 128, 56–92 (2017).

    Article  PubMed  Google Scholar 

  135. Huys, Q. J. M., Maia, T. V. & Frank, M. J. Computational psychiatry as a bridge from neuroscience to clinical applications. Nat. Neurosci. 19, 404–413 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Polanía, R., Krajbich, I., Grueschow, M. & Ruff, C. C. Neural oscillations and synchronization differentially support evidence accumulation in perceptual and value-based decision making. Neuron 82, 709–720 (2014).

    Article  PubMed  CAS  Google Scholar 

  137. Datta, A. et al. Gyri-precise head model of transcranial direct current stimulation: improved spatial focality using a ring electrode versus conventional rectangular pad. Brain Stimul. 2, 201–207.e1 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Thielscher, A., Opitz, A. & Windhoff, M. Impact of the gyral geometry on the electric field induced by transcranial magnetic stimulation. Neuroimage 54, 234–243 (2011).

    Article  PubMed  Google Scholar 

  139. Legon, W. et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat. Neurosci. 17, 322–329 (2014).

    Article  CAS  PubMed  Google Scholar 

  140. Opitz, A., Falchier, A., Linn, G. S., Milham, M. P. & Schroeder, C. E. Limitations of ex vivo measurements for in vivo neuroscience. Proc. Natl. Acad. Sci. USA 114, 5243–5246 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Day, B. L. et al. Electric and magnetic stimulation of human motor cortex: surface EMG and single motor unit responses. J. Physiol. (Lond.) 412, 449–473 (1989).

    Article  CAS  Google Scholar 

  142. Rossini, P. M. et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin. Neurophysiol. 126, 1071–1107 (2015).

    Article  CAS  PubMed  Google Scholar 

  143. Huang, Y. et al. Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. Elife 6, e18834 (2017).

    PubMed  PubMed Central  Google Scholar 

  144. Rahman, A., Lafon, B., Parra, L. C. & Bikson, M. Direct current stimulation boosts synaptic gain and cooperativity in vitro. J. Physiol. (Lond.) 595, 3535–3547 (2017).

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  146. Antal, A. et al. Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain. Neuroimage 85, 1040–1047 (2014).

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Cheeran, B. et al. A common polymorphism in the brain-derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS. J. Physiol. (Lond.) 586, 5717–5725 (2008).

    Article  CAS  Google Scholar 

  149. Malenka, R. C. & Bear, M. F. LTP and LTD: an embarrassment of riches. Neuron 44, 5–21 (2004).

    Article  CAS  PubMed  Google Scholar 

  150. Schwiedrzik, C. M. Retina or visual cortex? The site of phosphene induction by transcranial alternating current stimulation. Front. Integr. Neurosci 3, 6 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Michael A. Nitsche receives support by the EC Horizon 2020 Program, FET Grant, 686764-LUMINOUS, grants from the German ministry of Research and Education (GCBS grant 01EE1403C, TRAINSTIM grant 01GQ1424E), and by a grant from the Deutsche Forschungsgemeinschaft - Germany (SFB 1280 Extinction Learning). Christian C. Ruff is supported by the Swiss National Science Foundation (grants 105314_152891 and 100019L_173248) and by an ERC consolidator grant (BRAINCODES).

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Authors and Affiliations

  1. Laboratory for Social and Neural Systems Research (SNS-Lab), Department of Economics, University of Zurich, Zurich, Switzerland

    Rafael Polanía & Christian C. Ruff

  2. Leibniz Research Center for Working Environment and Human Factors, Department of Psychology and Neurosciences, TU Dortmund, Dortmund, Germany

    Michael A. Nitsche

  3. Department of Neurology, University Medical Hospital Bergmannsheil, Bochum, Germany

    Michael A. Nitsche

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  1. Rafael Polanía
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Polanía, R., Nitsche, M.A. & Ruff, C.C. Studying and modifying brain function with non-invasive brain stimulation. Nat Neurosci 21, 174–187 (2018). https://doi.org/10.1038/s41593-017-0054-4

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