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Transcranial direct current stimulation: State of the art 2008
Open accessAbstract
Effects of weak electrical currents on brain and neuronal function were first described decades ago. Recently, DC polarization of the brain was reintroduced as a noninvasive technique to alter cortical activity in humans. Beyond this, transcranial direct current stimulation (tDCS) of different cortical areas has been shown, in various studies, to result in modifications of perceptual, cognitive, and behavioral functions. Moreover, preliminary data suggest that it can induce beneficial effects in brain disorders. Brain stimulation with weak direct currents is a promising tool in human neuroscience and neurobehavioral research. To facilitate and standardize future tDCS studies, we offer this overview of the state of the art for tDCS.
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“tDCS is thought to affect neuroplasticity via modulating cellular, molecular and neurochemical mechanisms involved in use-dependent local and distant synaptic plasticity, i.e., GABA and glutamate-mediated long-term potentiation (Nitsche et al., 2008; Kim et al., 2014)”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Nitsche et al., 2008
In the citing paper
“Given that tDCS is thought to affect neuroplasticity (Nitsche et al., 2008; Kim et al., 2014),”
From Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder (ADHD) and Its Clinical Translation (2018) · cites this paper as Nitsche et al., 2008
In the citing paper
“Transcranial Direct Current Stimulation (tDCS) has been shown to be an effective non-invasive technique for research conducted with both healthy8 and clinical subjects9 in the domain of social cognition10.”
In the citing paper
“The effects of tDCS on neuronal excitability have now been demonstrated in numerous neuroimaging and physiological studies, providing a sound neurobiological basis for its use for neuromodulation in patient populations.1,3”
From Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial (2012) · cites this paper as [3]
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Cites
Nitsche, M. A., & Paulus, W. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00633.x · Cited by 5,656 · cited 4×
“For 4 seconds of tDCS, which elicits no after-effects, a break of 10 seconds between each period of stimulation is sufficient.(13) For tDCS durations that produce short-lasting (namely, for about 10 minutes) after-effects, a 1-hour break between stimulation sessions is sufficient.”
BackgroundResultInfluentialSelf-citationSustained excitability elevations induced by transcranial DC motor cortex stimulation in humans
Nitsche, M. A., & Paulus, W. (2001) · Neurology · doi:10.1212/wnl.57.10.1899 · Cited by 2,617 · cited 1×
“For tDCS durations resulting in long-lasting after-effects (1 hour or more), an intersession interval of 48 hours to 1 week has been suggested.(14,15,43) If repetitive tDCS is performed to prolong and stabilize long-lasting after-effects, subjects are generally stimulated once a day.”
BackgroundSelf-citationNitsche, M. A., Fricke, K., Henschke, U., Schlitterlau, A., Liebetanz, D., Lang, N., Henning, S. J., Tergau, F., & Paulus, W. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049916 · Cited by 1,587
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“Compared with TMS, it is easier to conduct placebo stimulation-controlled studies with tDCS, because, with the exception of a slight itching sensation and sensory phenomena, including retinal phosphenes with current switching, subjects rarely experience sensations related to the treatment.(26) To reduce cutaneous sens…”
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Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory
Fregni, F., Boggio, P. S., Nitsche, M., Bermpohl, F., Antal, A., Feredoes, E., Marcolin, M. A., Rigonatti, S. P., Silva, M. T. A., Paulus, W., et al. (2005) · Experimental Brain Research · doi:10.1007/s00221-005-2334-6 · Cited by 1,159 · cited 1×
“For tDCS durations resulting in long-lasting after-effects (1 hour or more), an intersession interval of 48 hours to 1 week has been suggested.(14,15,43) If repetitive tDCS is performed to prolong and stabilize long-lasting after-effects, subjects are generally stimulated once a day.”
BackgroundSelf-citationSafety aspects of transcranial direct current stimulation concerning healthy subjects and patients
Poreisz, C., Boros, K., Antal, A., & Paulus, W. (2007) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2007.01.004 · Cited by 1,153 · cited 3×
“Moreover, these protocols were tested in more than 2000-3000 subjects in laboratories worldwide with no serious side effects, except for a slight itching under the electrode, and seldom-occurring headache, fatigue, and nausea.(34) It is also possible that longer-lasting protocols are safe, because stimulation of up to…”
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Self-citationBindman, L. J., Lippold, O. C. J., & Redfearn, J. W. T. (1964) · The Journal of Physiology · doi:10.1113/jphysiol.1964.sp007425 · Cited by 969 · cited 2×
“With constant current density, increasing stimulation duration determined the occurrence and duration of after-effects in humans and animals.(3,13-15) Therefore tDCS protocols should state current strength and shape, electrode size, and stimulation duration for comparability between studies.”
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- Fregni, 2008, Cortical stimulation of the prefrontal cortex with transcranial direct current stimulation reduces cue-provoked smoking craving: a randomized, sham-controlled study, J Clin Psychiatry, 69, 32, 10.4088/JCP.v69n0105 · DOI
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Physiological basis of transcranial direct current stimulation
Stagg, C. J., & Nitsche, M. A. (2011) · The Neuroscientist · doi:10.1177/1073858410386614 · Cited by 1,719
Self-citationBrunoni, A. R., Nitsche, M. A., Bolognini, N., Bikson, M., Wagner, T., Merabet, L., Edwards, D. J., Valero-Cabre, A., Rotenberg, A., Pascual-Leone, A., et al. (2012) · Brain stimulation · doi:10.1016/j.brs.2011.03.002 · Cited by 1,445
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“…cm2, currents 1.5–2.1 mA) caused persisting skin lesions under the electrodes in some subjects, typically on the forehead or over frontal cortical areas (Frank et al. , 2010, Nitsche et al. , 2008, Palm et al. , 2008b, Riedel et al. , 2012, Rodriguez et al. , 2014, Wang et al. , 2015b) (Table 2).”
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Pino, G. D., Pellegrino, G., Assenza, G., Capone, F., Ferreri, F., Formica, D., Ranieri, F., Tombini, M., Ziemann, U., Rothwell, J. C., et al. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.162 · Cited by 1,027
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“Safety guidelines for using tDCS have been described by Nitsche et al. (2003) and by Bikson et al. (2009).”
Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG
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Self-citationPeters, S. K., Dunlop, K., & Downar, J. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00104 · Cited by 611
“A purely cortical mechanism of localized changes in synaptic plasticity is often postulated in the literature, given that the relatively weak electrical fields employed in tDCS may not penetrate beyond the cortex (Nitsche et al., 2008).”
BackgroundTranscranial electrical stimulation (tES – tDCS; tRNS, tACS) methods
Paulus, W. (2011) · Neuropsychological Rehabilitation · doi:10.1080/09602011.2011.557292 · Cited by 670
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Ultrasound Neuromodulation: A Review of Results, Mechanisms and Safety
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Modelling non-invasive brain stimulation in cognitive neuroscience
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Transcranial Direct Current Stimulation (tDCS): A Beginner's Guide for Design and Implementation
Thair, H., Holloway, A. L., Newport, R., & Smith, A. D. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00641 · Cited by 520
“The most commonly reported side effect is a cutaneous sensation (Poreisz et al., 2007), although this tends to subside once the current stabilizes (Nitsche et al., 2008).”
BackgroundInfluentialNon-invasive brain stimulation techniques for chronic pain
O'Connell, N. E., Wand, B. M., Marston, L., Spencer, S., & DeSouza, L. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008208.pub3 · Cited by 488
Li, L. M., Uehara, K., & Hanakawa, T. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00181 · Cited by 477
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Transcranial direct current stimulation for depression: 3-week, randomised, sham-controlled trial
Loo, C. K., Alonzo, A., Martin, D., Mitchell, P. B., Galvez, V., & Sachdev, P. (2012) · British Journal of Psychiatry · doi:10.1192/bjp.bp.111.097634 · Cited by 455
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“…by modulating neuron’s membrane resting potentials, and unable to directly depolarize neurons, it has to be applied for at least a few seconds (Nitsche and Paulus, 2000), and most generally, for a few minutes before an online impact can be observed on behavioral measures (Nitsche et al., 2008).”
BackgroundVal‐Laillet, D., Aarts, E., Weber, B., Ferrari, M., Quaresima, V., Stoeckel, L. E., Alonso‐Alonso, M., Audette, M. A., Malbert, C., & Stice, E. M. (2015) · NeuroImage Clinical · doi:10.1016/j.nicl.2015.03.016 · Cited by 466
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Self-citationNeurobiological after-effects of non-invasive brain stimulation
Cirillo, G., Di Pino, G., Capone, F., Ranieri, F., Florio, L., Todisco, V., Tedeschi, G., Funke, K., & Di Lazzaro, V. (2017) · Brain Stimulation · doi:10.1016/j.brs.2016.11.009 · Cited by 446
Kuo, M.-F., Paulus, W., & Nitsche, M. A. (2014) · NeuroImage · doi:10.1016/j.neuroimage.2013.05.117 · Cited by 415
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“It has been suggested that in some situations in which it is relevant to grantee the blinding procedure, it is possible to topically apply local anaesthetics (Nitsche et al., 2008; McFadden et al., 2011).”
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Self-citationPlasticity induced by non-invasive transcranial brain stimulation: a position paper
Huang, Y.-Z., Lu, M.-K., Antal, A., Classen, J., Nitsche, M., Ziemann, U., Ridding, M., Hamada, M., Ugawa, Y., Jaberzadeh, S., et al. (2017) · Clinical Neurophysiology · doi:10.1016/j.clinph.2017.09.007 · Cited by 401
“The after-effect of tDCS is thought to modulate cor- tical excitability in a polarity-specific manner (Nitsche et al., 2008).”
Self-citationRubia, K. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00100 · Cited by 384
“…cellular, molecular and neurochemical mechanisms involved in use-dependent local and distant synaptic plasticity, i.e., GABA and glutamate-mediated long-term potentiation (Nitsche et al., 2008; Kim et al., 2014), thought to underlie its long-term effects (Demirtas-Tatlidede et al., 2013).”
BackgroundNoninvasive Brain Stimulation Improves Language Learning
Flöel, A., Rösser, N., Michka, O., Knecht, S., & Breitenstein, C. (2008) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2008.20098 · Cited by 443
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Effects of tDCS on motor learning and memory formation: A consensus and critical position paper
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Self-citationModulating Neuronal Activity Produces Specific and Long-Lasting Changes in Numerical Competence
Kadosh, R. C., Soskic, S., Iuculano, T., Kanai, R., & Walsh, V. (2010) · Current Biology · doi:10.1016/j.cub.2010.10.007 · Cited by 392
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Random Noise Stimulation Improves Neuroplasticity in Perceptual Learning
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Direct Current Stimulation Modulates LTP and LTD: Activity Dependence and Dendritic Effects
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“11 tDCS’ is soma-hyperpolarizing and thus should reduce cortical excitability [35].”
Adverse events of tDCS and tACS: A review
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“…consisted of 10 sessions each of 0.3 mA cathodal stimulation for 16 min with bifrontal stimulus electrodes and the reference electrode on the leg, although the patient received 10 times the intended amperage, probably 3 mA (Lippold and Redfearn, 1964; Redfearn et al., 1964; Nitsche et al., 2008).”
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The electric field in the cortex during transcranial current stimulation
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Self-citationBidirectional alterations of interhemispheric parietal balance by non-invasive cortical stimulation
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tDCS selectively improves working memory in older adults with more education
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Does Transcranial Direct Current Stimulation Improve Healthy Working Memory?: A Meta-analytic Review
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“…anodal stimulation of the left dorsolateral pFC (DLPFC), a finding that makes sense given the tendency for anodal stimulation to enhance neuronal excitability (Nitsche et al., 2008; Priori, 2003; Nitsche & Paulus, 2000) and the role of the left DLPFC in WM (Carpenter, Just, & Reichle, 2000).”
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Fregni, F., Nitsche, M. A., Loo, C. K. A., Brunoni, A. R., Marangolo, P., Leite, J., Carvalho, S., Bolognini, N., Caumo, W., Paik, N., et al. (2014) · Clinical Research and Regulatory Affairs · doi:10.3109/10601333.2015.980944 · Cited by 292
Self-citationUltrasound Produces Extensive Brain Activation via a Cochlear Pathway
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Non-invasive Cerebellar Stimulation—a Consensus Paper
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Self-citationNaming facilitation induced by transcranial direct current stimulation
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Self-citationDifferences in the experience of active and sham transcranial direct current stimulation
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Self-citationModulation of motor performance and motor learning by transcranial direct current stimulation
Reis, J., & Fritsch, B. (2011) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32834c3db0 · Cited by 276
Non-invasive brain stimulation techniques for chronic pain
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Inferring Causality from Noninvasive Brain Stimulation in Cognitive Neuroscience
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“Stimulation intensity and duration are crucial determinants for offline effects with both TMS (Ziemann et al., 2008) and TCS (Nitsche et al., 2008).”
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Brain-derived neurotrophic factor (BDNF) gene polymorphisms shape cortical plasticity in humans
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Neuromodulation for Brain Disorders: Challenges and Opportunities
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Transcranial direct current stimulation over the primary motor cortex during fMRI
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Self-citationTDCS increases cortical excitability: Direct evidence from TMS–EEG
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Self-citationBrain networks and their relevance for stroke rehabilitation
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State-dependent effects of neural stimulation on brain function and cognition
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The neuroethics of non-invasive brain stimulation
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The Uncertain Outcome of Prefrontal tDCS
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Brain circuits for pain and its treatment
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Transcranial direct current stimulation (tDCS) in a realistic head model
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Transcranial direct current stimulation in severe, drug-resistant major depression
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Self-citationTranscranial direct current stimulation (tDCS) and language
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“…TDCS can either de-or hyperpolarize a neuron ’ s resting membrane potential: anodal TDCS (aTDCS) is thought to depolarize neurons and thereby increases corticomotor excitability, whereas cathodal tDCS (cTDCS) hyperpolarizes the resting membrane, causing a decreased corticomotor excitability [16].”
Basic and functional effects of transcranial Electrical Stimulation (tES)—An introduction
Yavari, F., Jamil, A., Mosayebi-Samani, M., Vidor, L. P., & Nitsche, M. A. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.06.015 · Cited by 242
“Our intention here is not to present a complete overview, but to discuss the principle mechanisms (a more comprehensive overview can be found in (Floel, 2014; Kuo and Nitsche, 2012; Nitsche et al., 2008; Reis and Fritsch, 2011; Reis et al., 2008)).”
BackgroundSelf-citationConcurrent cognitive control training augments the antidepressant efficacy of tDCS: A pilot study
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Mulquiney, P. G., Hoy, K., Daskalakis, Z., & Fitzgerald, P. (2011) · Clinical Neurophysiology · doi:10.1016/j.clinph.2011.05.009 · Cited by 230
Metadata
- Authors
- Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A., Paulus, W., Hummel, F., Boggio, P. S., Fregni, F., & Pascual-Leone, A.
- Affiliations
- University of Göttingen (DE)
- National Institutes of Health (US)
- University of Milan (IT)
- Christian-Albrechts-Universität zu Kiel (DE)
- Universität Hamburg (DE)
- Universidade Presbiteriana Mackenzie (BR)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Nitsche, Michael A.
- ORCID
- Venue
- Brain Stimulation
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 1
- Issue
- 3
- Pages
- 206-223
- ISSN
- 1876-4754 (ISSN-L)
- 1935-861X
- OpenAlex
- W2162932719
- Cited by
- 3,057
- References
- 122
- Citations by year
- 2026: 110 · 2025: 166 · 2024: 152 · 2023: 175 · 2022: 168 · 2021: 218 · 2020: 233 · 2019: 298 · 2018: 239 · 2017: 208 · 2016: 234 · 2015: 227 · 2014: 181 · 2013: 172 · 2012: 113
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Brain stimulation (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- transcranial direct current stimulation, non-invasive brain stimulation, cortical excitability, behavioral effects, brain disorders
- MeSH terms
- Animals, Cerebral Cortex, Transcutaneous Electric Nerve Stimulation, Humans, Research Design, Transcranial Magnetic Stimulation
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