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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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).
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).
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).
Fenno, L., Yizhar, O. & Deisseroth, K. The development and application of optogenetics. Annu. Rev. Neurosci. 34, 389–412 (2011).
Merton, P. A. & Morton, H. B. Stimulation of the cerebral cortex in the intact human subject. Nature 285, 227 (1980).
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).
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).
Kar, K. & Krekelberg, B. Transcranial electrical stimulation over visual cortex evokes phosphenes with a retinal origin. J. Neurophysiol. 108, 2173–2178 (2012).
Kar, K., Duijnhouwer, J. & Krekelberg, B. Transcranial alternating current stimulation attenuates neuronal adaptation. J. Neurosci. 37, 2325–2335 (2017).
Hallett, M. Transcranial magnetic stimulation: a primer. Neuron 55, 187–199 (2007).
Amassian, V. E. et al. Suppression of visual perception by magnetic coil stimulation of human occipital cortex. Electroencephalogr. Clin. Neurophysiol. 74, 458–462 (1989).
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).
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).
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).
Blankenburg, F. et al. Studying the role of human parietal cortex in visuospatial attention with concurrent TMS-fMRI. Cereb. Cortex 20, 2702–2711 (2010).
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).
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).
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).
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).
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).
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).
Ueyama, E. et al. Chronic repetitive transcranial magnetic stimulation increases hippocampal neurogenesis in rats. Psychiatry Clin. Neurosci 65, 77–81 (2011).
Silvanto, J., Muggleton, N. & Walsh, V. State-dependency in brain stimulation studies of perception and cognition. Trends Cogn. Sci. 12, 447–454 (2008).
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).
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).
Pascual-Leone, A. & Walsh, V. Fast backprojections from the motion to the primary visual area necessary for visual awareness. Science 292, 510–512 (2001).
Hallett, M. Plasticity of the human motor cortex and recovery from stroke. Brain Res. Brain Res. Rev. 36, 169–174 (2001).
Chen, R., Cohen, L. G. & Hallett, M. Nervous system reorganization following injury. Neuroscience 111, 761–773 (2002).
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).
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).
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).
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).
Nitsche, M. A. & Paulus, W. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans. Neurology 57, 1899–1901 (2001).
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).
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).
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).
Siegel, M., Donner, T. H. & Engel, A. K. Spectral fingerprints of large-scale neuronal interactions. Nat. Rev. Neurosci. 13, 121–134 (2012).
Antal, A. & Paulus, W. Transcranial alternating current stimulation (tACS). Front. Hum. Neurosci. 7, 317 (2013).
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).
Ozen, S. et al. Transcranial electric stimulation entrains cortical neuronal populations in rats. J. Neurosci. 30, 11476–11485 (2010).
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).
Cecere, R., Rees, G. & Romei, V. Individual differences in alpha frequency drive crossmodal illusory perception. Curr. Biol. 25, 231–235 (2015).
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).
Minami, S. & Amano, K. Illusory jitter perceived at the frequency of alpha oscillations. Curr. Biol. 27, 2344–2351.e4 (2017).
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).
Santarnecchi, E. et al. Frequency-dependent enhancement of fluid intelligence induced by transcranial oscillatory potentials. Curr. Biol. 23, 1449–1453 (2013).
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).
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).
Violante, I. R. et al. Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance. Elife 6, 91–95 (2017).
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).
Romei, V., Gross, J. & Thut, G. Sounds reset rhythms of visual cortex and corresponding human visual perception. Curr. Biol. 22, 807–813 (2012).
Berényi, A., Belluscio, M., Mao, D. & Buzsáki, G. Closed-loop control of epilepsy by transcranial electrical stimulation. Science 337, 735–737 (2012).
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).
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).
Roth, Y., Zangen, A. & Hallett, M. A coil design for transcranial magnetic stimulation of deep brain regions. J. Clin. Neurophysiol. 19, 361–370 (2002).
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).
Grossman, N. et al. Noninvasive deep brain stimulation via temporally interfering electric Fields. Cell 169, 1029–1041.e16 (2017).
Noury, N. & Siegel, M. Phase properties of transcranial electrical stimulation artifacts in electrophysiological recordings. Neuroimage 158, 406–416 (2017).
Noury, N., Hipp, J. F. & Siegel, M. Physiological processes non-linearly affect electrophysiological recordings during transcranial electric stimulation. Neuroimage 140, 99–109 (2016).
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).
Fertonani, A., Pirulli, C. & Miniussi, C. Random noise stimulation improves neuroplasticity in perceptual learning. J. Neurosci. 31, 15416–15423 (2011).
Saiote, C., Polanía, R., Rosenberger, K., Paulus, W. & Antal, A. High-frequency TRNS reduces BOLD activity during visuomotor learning. PLoS One 8, e59669 (2013).
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).
Miniussi, C., Harris, J. A. & Ruzzoli, M. Modelling non-invasive brain stimulation in cognitive neuroscience. Neurosci. Biobehav. Rev. 37, 1702–1712 (2013).
Silvanto, J., Cowey, A., Lavie, N. & Walsh, V. Striate cortex (V1) activity gates awareness of motion. Nat. Neurosci. 8, 143–144 (2005).
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).
Muellbacher, W. et al. Early consolidation in human primary motor cortex. Nature 415, 640–644 (2002).
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).
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).
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).
Tarapore, P. E. et al. Language mapping with navigated repetitive TMS: proof of technique and validation. Neuroimage 82, 260–272 (2013).
Holland, R. et al. Speech facilitation by left inferior frontal cortex stimulation. Curr. Biol. 21, 1403–1407 (2011).
Sparing, R. et al. Bidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation. Brain 132, 3011–3020 (2009).
Ashbridge, E., Walsh, V. & Cowey, A. Temporal aspects of visual search studied by transcranial magnetic stimulation. Neuropsychologia 35, 1121–1131 (1997).
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).
Wang, J. X. et al. Targeted enhancement of cortical-hippocampal brain networks and associative memory. Science 345, 1054–1057 (2014).
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).
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).
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).
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).
Strang, S. et al. Be nice if you have to—the neurobiological roots of strategic fairness. Soc. Cogn. Affect. Neurosci. 10, 790–796 (2015).
Ruff, C. C., Ugazio, G. & Fehr, E. Changing social norm compliance with noninvasive brain stimulation. Science 342, 482–484 (2013).
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).
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).
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).
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).
Rioult-Pedotti, M. S., Friedman, D. & Donoghue, J. P. Learning-induced LTP in neocortex. Science 290, 533–536 (2000).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Monte-Silva, K. et al. D2 receptor block abolishes θ burst stimulation-induced neuroplasticity in the human motor cortex. Neuropsychopharmacology 36, 2097–2102 (2011).
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).
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).
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).
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).
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).
Woods, A. J. et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin. Neurophysiol. 127, 1031–1048 (2016).
Schmidt, F.L. & Hunter, J.E. Methods of Meta-analysis: Correcting Error and Bias in Research Findings (Sage, Thousand Oaks, CA, USA, 2014).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Reardon, S. ‘Brain doping’ may improve athletes’ performance. Nature 531, 283–284 (2016).
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).
Fitz, N. S. & Reiner, P. B. The challenge of crafting policy for do-it-yourself brain stimulation. J. Med. Ethics 41, 410–412 (2015).
Hill, C. A. et al. A causal account of the brain network computations underlying strategic social behavior. Nat. Neurosci. 20, 1142–1149 (2017).
Rose, N. S. et al. Reactivation of latent working memories with transcranial magnetic stimulation. Science 354, 1136–1139 (2016).
Barron, H. C. et al. Unmasking latent inhibitory connections in human cortex to reveal dormant cortical memories. Neuron 90, 191–203 (2016).
Thut, G. et al. Rhythmic TMS causes local entrainment of natural oscillatory signatures. Curr. Biol. 21, 1176–1185 (2011).
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).
Stagg, C. J., Bachtiar, V. & Johansen-Berg, H. The role of GABA in human motor learning. Curr. Biol. 21, 480–484 (2011).
Stagg, C. J. et al. Polarity-sensitive modulation of cortical neurotransmitters by transcranial stimulation. J. Neurosci. 29, 5202–5206 (2009).
Trepel, C. & Racine, R. J. GABAergic modulation of neocortical long-term potentiation in the freely moving rat. Synapse 35, 120–128 (2000).
Open Science Collaboration. Estimating the reproducibility of psychological science. Science 349, aac4716 (2015).
Button, K. S. et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat. Rev. Neurosci. 14, 365–376 (2013).
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).
Morbidi, F. et al. Off-line removal of TMS-induced artifacts on human electroencephalography by Kalman filter. J. Neurosci. Methods 162, 293–302 (2007).
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).
Kanai, R., Chaieb, L., Antal, A., Walsh, V. & Paulus, W. Frequency-dependent electrical stimulation of the visual cortex. Curr. Biol. 18, 1839–1843 (2008).
Fostering reproducible fMRI research. Nat. Commun. 8, 14748 (2017).
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).
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).
Lefaucheur, J.-P. et al. Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS). Clin. Neurophysiol. 128, 56–92 (2017).
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).
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).
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).
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).
Legon, W. et al. Transcranial focused ultrasound modulates the activity of primary somatosensory cortex in humans. Nat. Neurosci. 17, 322–329 (2014).
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).
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).
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).
Huang, Y. et al. Measurements and models of electric fields in the in vivo human brain during transcranial electric stimulation. Elife 6, e18834 (2017).
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).
Tufail, Y. et al. Transcranial pulsed ultrasound stimulates intact brain circuits. Neuron 66, 681–694 (2010).
Antal, A. et al. Imaging artifacts induced by electrical stimulation during conventional fMRI of the brain. Neuroimage 85, 1040–1047 (2014).
Fritsch, B. et al. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning. Neuron 66, 198–204 (2010).
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).
Malenka, R. C. & Bear, M. F. LTP and LTD: an embarrassment of riches. Neuron 44, 5–21 (2004).
Schwiedrzik, C. M. Retina or visual cortex? The site of phosphene induction by transcranial alternating current stimulation. Front. Integr. Neurosci 3, 6 (2009).
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).
The authors declare no competing financial interests.
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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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