Top Ten tDCS Papers of All Time

1

1. Transcranial direct current stimulation: state of the art 2008

MA Nitsche, LG Cohen, EM Wassermann, A Priori et al.

Year: 2008
Citations per year: 145.38
Total Citations: 1163
Abstract 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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2

2. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation 2000

MA Nitsche, W Paulus

Year: 2000
Citations per year: 131.75
Total Citations: 2108
Abstract In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp. Excitability changes of up to 40 %, revealed by transcranial magnetic stimulation, were accomplished and lasted for several minutes after the end of current stimulation. Excitation could be achieved selectively by anodal stimulation, and inhibition by cathodal stimulation. By varying the current intensity and duration, the strength and duration of the after-effects could be controlled. The effects were probably induced by modification of membrane polarisation. Functional alterations related to post-tetanic potentiation, short-term potentiation and processes similar to postexcitatory central inhibition are the likely candidates for the excitability changes after the end of stimulation. Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive, painless, reversible, selective and focal way.
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3

3. Clinical research with transcranial direct current stimulation (tDCS): challenges and future directions

AR Brunoni, MA Nitsche, N Bolognini, M Bikson et al.

Year: 2012
Citations per year: 111.5
Total Citations: 446
Abstract BACKGROUND: Transcranial direct current stimulation (tDCS) is a neuromodulatory technique that delivers low-intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity. In the past 10 years, tDCS physiologic mechanisms of action have been intensively investigated giving support for the investigation of its applications in clinical neuropsychiatry and rehabilitation. However, new methodologic, ethical, and regulatory issues emerge when translating the findings of preclinical and phase I studies into phase II and III clinical studies. The aim of this comprehensive review is to discuss the key challenges of this process and possible methods to address them. METHODS: We convened a workgroup of researchers in the field to review, discuss, and provide updates and key challenges of tDCS use in clinical research. MAIN FINDINGS/DISCUSSION: We reviewed several basic and clinical studies in the field and identified potential limitations, taking into account the particularities of the technique. We review and discuss the findings into four topics: (1) mechanisms of action of tDCS, parameters of use and computer-based human brain modeling investigating electric current fields and magnitude induced by tDCS; (2) methodologic aspects related to the clinical research of tDCS as divided according to study phase (ie, preclinical, phase I, phase II, and phase III studies); (3) ethical and regulatory concerns; and (4) future directions regarding novel approaches, novel devices, and future studies involving tDCS. Finally, we propose some alternative methods to facilitate clinical research on tDCS.
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4. Evidence that transcranial direct current stimulation (tDCS) generates little-to-no reliable neurophysiologic effect beyond MEP amplitude modulation in healthy human …

JC Horvath, JD Forte, O Carter

Year: 2015
Citations per year: 100
Total Citations: 100
Abstract

BACKGROUND: Over the last 15-years, transcranial direct current stimulation (tDCS), a relatively novel form of neuromodulation, has seen a surge of popularity in both clinical and academic settings. Despite numerous claims suggesting that a single session of tDCS can modulate cognition in healthy adult populations (especially working memory and language production), the paradigms utilized and results reported in the literature are extremely variable. To address this, we conduct the largest quantitative review of the cognitive data to date.

METHODS: Single-session tDCS data in healthy adults (18–50) from every cognitive outcome measure reported by at least two different research groups in the literature was collected. Outcome measures were divided into 4 broad categories: executive function, language, memory, and miscellaneous. To account for the paradigmatic variability in the literature, we undertook a three-tier analysis system; each with less-stringent inclusion criteria than the prior. Standard mean difference values with 95% CIs were generated for included studies and pooled for each analysis.

RESULTS: Of the 59 analyses conducted, tDCS was found to not have a significant effect on any – regardless of inclusion laxity. This includes no effect on any working memory outcome or language production task.

CONCLUSION: Our quantitative review does not support the idea that tDCS generates a reliable effect on cognition in healthy adults. Reasons for and limitations of this finding are discussed. This work raises important questions regarding the efficacy of tDCS, state-dependency effects, and future directions for this tool in cognitive research.

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5

Physiological basis of transcranial direct current stimulation, 2011

CJ Stagg, MA Nitsche

Year: 2011
Citations per year: 96.6
Total Citations: 483
Abstract Since the rediscovery of transcranial direct current stimulation (tDCS) about 10 years ago, interest in tDCS has grown exponentially. A noninvasive stimulation technique that induces robust excitability changes within the stimulated cortex, tDCS is increasingly being used in proof-of-principle and stage IIa clinical trials in a wide range of neurological and psychiatric disorders. Alongside these clinical studies, detailed work has been performed to elucidate the mechanisms underlying the observed effects. In this review, the authors bring together the results from these pharmacological, neurophysiological, and imaging studies to describe their current knowledge of the physiological effects of tDCS. In addition, the theoretical framework for how tDCS affects motor learning is proposed.
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6

6. Finite-element model predicts current density distribution for clinical applications of tDCS and tACS

T Neuling, S Wagner, CH Wolters et al

Year: 2015
Citations per year: 90
Total Citations: 90
Abstract Transcranial direct current stimulation (tDCS) has been applied in numerous scientific studies over the past decade. However, the possibility to apply tDCS in therapy of neuropsychiatric disorders is still debated. While transcranial magnetic stimulation (TMS) has been approved for treatment of major depression in the United States by the Food and Drug Administration (FDA), tDCS is not as widely accepted. One of the criticisms against tDCS is the lack of spatial specificity. Focality is limited by the electrode size (35 cm(2) are commonly used) and the bipolar arrangement. However, a current flow through the head directly from anode to cathode is an outdated view. Finite-element (FE) models have recently been used to predict the exact current flow during tDCS. These simulations have demonstrated that the current flow depends on tissue shape and conductivity. To face the challenge to predict the location, magnitude, and direction of the current flow induced by tDCS and transcranial alternating current stimulation (tACS), we used a refined realistic FE modeling approach. With respect to the literature on clinical tDCS and tACS, we analyzed two common setups for the location of the stimulation electrodes which target the frontal lobe and the occipital lobe, respectively. We compared lateral and medial electrode configuration with regard to their usability. We were able to demonstrate that the lateral configurations yielded more focused stimulation areas as well as higher current intensities in the target areas. The high resolution of our simulation allows one to combine the modeled current flow with the knowledge of neuronal orientation to predict the consequences of tDCS and tACS. Our results not only offer a basis for a deeper understanding of the stimulation sites currently in use for clinical applications but also offer a better interpretation of observed effects.
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7

Quantitative review finds no evidence of cognitive effects in healthy populations from single-session transcranial direct current stimulation (tDCS)

JC Horvath, JD Forte, O Carter

Year: 2015
Citations per year: 89
Total Citations: 89
Abstract Transcranial direct current stimulation (tDCS) has been applied in numerous scientific studies over the past decade. However, the possibility to apply tDCS in therapy of neuropsychiatric disorders is still debated. While transcranial magnetic stimulation (TMS) has been approved for treatment of major depression in the United States by the Food and Drug Administration (FDA), tDCS is not as widely accepted. One of the criticisms against tDCS is the lack of spatial specificity. Focality is limited by the electrode size (35 cm(2) are commonly used) and the bipolar arrangement. However, a current flow through the head directly from anode to cathode is an outdated view. Finite-element (FE) models have recently been used to predict the exact current flow during tDCS. These simulations have demonstrated that the current flow depends on tissue shape and conductivity. To face the challenge to predict the location, magnitude, and direction of the current flow induced by tDCS and transcranial alternating current stimulation (tACS), we used a refined realistic FE modeling approach. With respect to the literature on clinical tDCS and tACS, we analyzed two common setups for the location of the stimulation electrodes which target the frontal lobe and the occipital lobe, respectively. We compared lateral and medial electrode configuration with regard to their usability. We were able to demonstrate that the lateral configurations yielded more focused stimulation areas as well as higher current intensities in the target areas. The high resolution of our simulation allows one to combine the modeled current flow with the knowledge of neuronal orientation to predict the consequences of tDCS and tACS. Our results not only offer a basis for a deeper understanding of the stimulation sites currently in use for clinical applications but also offer a better interpretation of observed effects.
Full paper »

8

8. Direct current stimulation promotes BDNF-dependent synaptic plasticity: potential implications for motor learning

B Fritsch, J Reis, K Martinowich, HM Schambra

Year: 2010
Citations per year: 86.83
Total Citations: 521
Abstract Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.
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9

Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation

J Reis, HM Schambra, LG Cohen et al.

Year: 2009
Citations per year: 86.57
Total Citations: 606
Abstract Despite its increasing use in experimental and clinical settings, the cellular and molecular mechanisms underlying transcranial direct current stimulation (tDCS) remain unknown. Anodal tDCS applied to the human motor cortex (M1) improves motor skill learning. Here, we demonstrate in mouse M1 slices that DCS induces a long-lasting synaptic potentiation (DCS-LTP), which is polarity specific, NMDA receptor dependent, and requires coupling of DCS with repetitive low-frequency synaptic activation (LFS). Combined DCS and LFS enhance BDNF-secretion and TrkB activation, and DCS-LTP is absent in BDNF and TrkB mutant mice, suggesting that BDNF is a key mediator of this phenomenon. Moreover, the BDNF val66met polymorphism known to partially affect activity-dependent BDNF secretion impairs motor skill acquisition in humans and mice. Motor learning is enhanced by anodal tDCS, as long as activity-dependent BDNF secretion is in place. We propose that tDCS may improve motor skill learning through augmentation of synaptic plasticity that requires BDNF secretion and TrkB activation within M1.
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10

10 Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans

MA Nitsche, W Paulus

Year: 2001
Citations per year: 78.73
Total Citations: 1181
Abstract The authors show that in the human transcranial direct current stimulation is able to induce sustained cortical excitability elevations. As revealed by transcranial magnetic stimulation, motor cortical excitability increased approximately 150% above baseline for up to 90 minutes after the end of stimulation. The feasibility of inducing long-lasting excitability modulations in a noninvasive, painless, and reversible way makes this technique a potentially valuable tool in neuroplasticity modulation.
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