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Objective . Transcranial electrical stimulation (tES) is a promising method for modulating brain activity and excitability with variable results to date. To minimize electric (E-)field strength variability, we introduce the 2-sample prospective E-field dosing (2-SPED) approach, which uses E-field strengths induced by tES in a first population to individualize stimulation intensity in a second population. Approach . We performed E-field modeling of three common tES montages in 300 healthy younger adults. First, permutation analyses identified the sample size required to obtain a stable group average E-field in the primary motor cortex (M1), with stability being defined as the number of participants where all group-average E-field strengths ± standard deviation did not leave the population's 5-95 percentile range. Second, this stable group average was used to individualize tES intensity in a second independent population (n = 100). The impact of individualized versus fixed intensity tES on E-field strength variability was analyzed. Main results . In the first population, stable group average E-field strengths (V/m) in M1 were achieved at 74-85 participants, depending on the tES montage. Individualizing the stimulation intensity (mA) in the second population resulted in uniform M1 E-field strength (all p < 0.001) and significantly diminished peak cortical E-field strength variability (all p < 0.01), across all montages. Significance . 2-SPED is a feasible way to prospectively induce more uniform E-field strengths in a region of interest. Future studies might apply 2-SPED to investigate whether decreased E-field strength variability also results in decreased physiological and behavioral variability in response to tES., (Creative Commons Attribution license.)

Attention bias is a tendency to preferably detect, orient and select emotionally valued stimuli, as compared to neutral stimuli, and plays a crucial role in the psychopathology of various psychiatric disorders. Transcranial direct current stimulation (tDCS) has been applied for the alteration of attention bias in health and disease with different parameters and conditions, but the contribution of these factors to the magnitude and directionality of effects has not previously been comprehensively reviewed. In this review, we aimed to systematically explore the effects of tDCS on attention bias in different tasks, tDCS conditions, and health states. Data were collected in accordance with the PRISMA approach. A literature search identified 22 original experiments that explored the effects of tDCS on attention bias. Determinants of tDCS effects on attention bias were cortical target areas, the specific task under study, stimulation parameters, and the presence of psychopathology. Relevant cortical areas for modification of attention bias via tDCS were the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC). The observed heterogeneity of the impact of tDCS on the modulation of attention bias can be explained by the area of stimulation, valence of stimuli, task characteristics, and the intensity of stimulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Stuttering is a disorder that begins in childhood and can persist into adulthood. In the present study, it was hypothesized that the combined intervention of transcranial direct current stimulation (tDCS) and Delayed Auditory Feedback (DAF) would cause greater improvement in speech fluency in comparison to the intervention with DAF alone., Methods: A randomized, double-blind, sham-controlled clinical trial was conducted to investigate the effects of the combined intervention. Fifty adults with moderate to severe stuttering (25 females, 25 males, Mean age=26.92, SD=6.23) were randomly allocated to the anodal or sham tDCS group. In the anodal tDCS group, participants received DAF combined with anodal tDCS (1 mA), while the sham tDCS group was exposed to sham tDCS simultaneously with DAF. In this study, a 60-ms delay was used for DAF intervention, and tDCS was applied over the left superior temporal gyrus. Each individual participated in six 20-minute intervention sessions (held on six consecutive days). Speech fluency was assessed before and after the intervention., Results: In the anodal tDCS group, the scores of the Stuttering Severity Instrument, Overall Assessment of the Speaker's Experience of Stuttering questionnaire, and the percentage of stuttered syllable reduced significantly (from average baseline rates of 8.45%, across three tasks, to 5.36% at the follow-up assessment) after the intervention., Conclusion: The results of this study suggest that delivery of anodal tDCS when combined with DAF may enhance stuttering reduction effects for six weeks following the intervention., (Copyright © 2022. Published by Elsevier Inc.)

Background: Individuals with major depressive disorder (MDD) have deficits in emotion regulation, which plays a putative role in psychopathology. The ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) are assumed to be involved in respective processes. In the present study, we aimed to explore the effect of stimulation over the dlPFC and vmPFC on emotion regulation in female with MDD., Material and Methods: Twenty women with MDD performed the Emotional Stroop, Emotional Go/No-Go, and Emotional 1-Back tasks during transcranial direct current stimulation (tDCS) in three separate sessions with the following electrode montages: anodal dlPFC (F3)/cathodal vmPFC (Fp2), anodal vmPFC (Fp2)/cathodal dlPFC (F3), and sham stimulation., Results: Independent of the valence of the respective stimuli, accuracy and speed of interference control, accuracy of pre-potent inhibition, and accuracy, but not speed, of working memory performance improved during anodal left dlPFC/cathodal right vmPFC stimulation. Independent of stimulation conditions, interference control was reduced for sad faces, as compared to happy and neutral faces, and working memory performance was faster for happy than for neutral and sad faces. For the impact of stimulation on specific emotional qualities, anodal left dlPFC/cathodal right vmPFC, compared to sham stimulation, led to improved interference control of sad and neutral faces in the emotional Stroop task, as shown by faster reaction times. Furthermore, in that task accuracy with respect to neutral and happy face conditions was higher during both real stimulation conditions, as compared to sham stimulation., Conclusion: The dlPFC is involved in emotion regulation in MDD. Emotional valence is moreover relevant for the effect of stimulation over this area on interference control in MDD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: and purpose of the study: Individuals with general anxiety disorder (GAD) have deficits in emotional and cognitive processing, including cognitive bias, which plays a causal role in anxiety. Hyperactivity of the ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) is assumed to be involved in cognitive bias. We aimed to explore the causal contribution of the dorsolateral and ventromedial prefrontal cortices (dlPFC, vmPFC) on cognitive bias via non-invasive brain stimulation, and expected a bias-reducing effect of cortical activity enhancement over these areas in GAD, with a larger contribution of the vmPFC to perceptual, and of the dlPFC to interpretation bias., Material and Methods: The study was conducted in a randomized, single-blinded, and complete crossover design. Thirty-four adults with GAD, received transcranial direct current stimulation (tDCS) in 5 separate sessions (1.5 mA, 20 min) with the following electrode montages: anodal dlPFC/cathodal vmPFC, anodal vmPFC/cathodal dlPFC, anodal dlPFC/cathodal right shoulder, anodal vmPFC/cathodal left shoulder, and sham stimulation. During stimulation, in each session, participants performed the Dot-Probe and Reading Mind from Eyes tests to measure attention and interpretation biases., Results: A significant effect of stimulation condition on attention and interpretation biases was observed. Anodal vmPFC and dlPFC stimulation coupled with an extracranial cathodal electrode reduced attention bias to threat-related stimuli in the dot-probe test. Furthermore, anodal dlPFC/cathodal vmPFC stimulation reduced negative interpretation bias in reading from eyes test., Conclusion: As suggested by the results of this study, both dlPFC and vmPFC are involved in cognitive bias in GAD, but with partially different roles. Anodal stimulation over the right vmPFC and the left dlPFC reduced attention bias, supporting the relevance of these areas for attention bias. For interpretation bias, the significant effect of anodal dlPFC/cathodal vmPFC stimulation, but only trendwise effect of anodal tDCS over the dlPFC combined with an extracephalic return electrode is in accordance with a predominant effect of the dlPFC on interpretation bias, but does not rule out an additional minor involvement of the vmPFC. Based on these results, a new model is suggested for the neural underpinnings of anxiety symptoms., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

During transcranial electric stimulation, increasing intracellular Ca 2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca 2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of "leaky membranes" under activation, surround inhibition, intracellular Ca 2+ increase, and their role in the aftereffects of tACS. NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca 2+ concentration alterations.

The brain is a dynamic organ whose growth and organization varies according to each subject's life experiences. Through adaptations in gene expression and the release of neurotrophins and neurotransmitters, these experiences induce a process of cellular realignment and neural network reorganization, which consolidate what is called neuroplasticity. However, despite the brain's resilience and dynamism, neuroplasticity is maximized during the first years of life, when the developing brain is more sensitive to structural reorganization and the repair of damaged neurons. This review presents an overview of non-invasive brain stimulation (NIBS) techniques that have increasingly been a focus for experimental research and the development of therapeutic methods involving neuroplasticity, especially Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS). Due to its safety risk profile and extensive tolerability, several trials have demonstrated the benefits of NIBS as a feasible experimental alternative for the treatment of brain and mind disorders in children and adolescents. However, little is known about the late impact of neuroplasticity-inducing tools on the developing brain, and there are concerns about aberrant plasticity. There are also ethical considerations when performing interventions in the pediatric population. This article will therefore review these aspects and also obstacles related to the premature application of NIBS, given the limited evidence available concerning the extent to which these methods interfere with the developing brain., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transcranial alternating current stimulation (tACS) has been shown to modulate neural oscillations and excitability levels in the primary motor cortex (M1). These effects can last for more than an hour and an involvement of N-methyl-d-aspartate receptor (NMDAR) mediated synaptic plasticity has been suggested. However, to date the cortical mechanisms underlying tACS after-effects have not been explored. Here, we applied 20 Hz beta tACS to M1 while participants received either the NMDAR antagonist dextromethorphan or a placebo and the effects on cortical beta oscillations and excitability were explored. When a placebo medication was administered, beta tACS was found to increase cortical excitability and beta oscillations for at least 60 min, whereas when dextromethorphan was administered, these effects were completely abolished. These results provide the first direct evidence that tACS can induce NMDAR-mediated plasticity in the motor cortex, which contributes to our understanding of tACS-induced influences on human motor cortex physiology., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Transcranial direct current stimulation (tDCS) is a noninvasive method that delivers current through the scalp to enhance or suppress brain activity. The standard way of applying tDCS is by the use of two large rectangular sponge electrodes on the scalp. The resulting currents often stimulate a broad region of the brain distributed over brain networks. In order to address this issue, recently, multi-electrode transcranial direct current stimulation with optimized montages has been used to stimulate brain regions of interest (ROI) with improved trade-off between focality and intensity of the electrical current at the target brain region. However, in many cases only the location of target region is considered and not the orientation. Here we emphasize the importance of calculating the individualized target location and orientation by combined electroencephalography and magnetoencephalography (EMEG) source analysis in individualized skull-conductivity calibrated finite element method (FEM) head models and stimulate the target region by four different tDCS montages. We have chosen the generator of the P20/N20 component, located at Brodmann area 3b and oriented mainly from posterior to anterior directions as our target for stimulation because it can be modeled as a single dipole source with a fixed position and orientation. The simulations will deliver optimized excitatory and inhibitory electrode montages that are in future investigations compared to standard and sham tDCS in a somatosensory experiment. We also present a new constrained maximum intensity (CMI) optimization approach that better distributes the currents over multiple electrodes, therefore should lead to less tingling and burning sensations at the skin, and thus allows an easier realization of the sham condition significantly reducing the current intensity parallel to the target.

Background: Transcranial direct current stimulation (tDCS) can enhance cognitive function in healthy individuals, with promising applications as a therapeutic intervention. Despite this potential, variability in the efficacy of tDCS has been a considerable concern., Objective: /Hypothesis: Given that tDCS is always applied at a set intensity, we examined whether individual differences in sensitivity to brain stimulation might be one variable that modulates the efficacy of tDCS in a motor learning task., Methods: In the first part of the experiment, single-pulse transcranial magnetic stimulation (TMS) over primary motor cortex (M1) was used to determine each participant's resting motor threshold (rMT). This measure was used as a proxy of individual sensitivity to brain stimulation. In an experimental group of 28 participants, 2 mA tDCS was then applied during a motor learning task with the anodal electrode positioned over left M1. Another 14 participants received sham stimulation., Results: M1-Anodal tDCS facilitated learning relative to participants who received sham stimulation. Of primary interest was a within-group analysis of the experimental group, showing that the rate of learning was positively correlated with rMT: Participants who were more sensitive to brain stimulation as operationalized by our TMS proxy (low rMT), showed faster adaptation., Conclusions: Methodologically, the results indicate that TMS sensitivity can predict tDCS efficacy in a behavioral task, providing insight into one source of variability that may contribute to replication problems with tDCS. Theoretically, the results provide further evidence of a role of sensorimotor cortex in adaptation, with the boost from tDCS observed during acquisition., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The interest in the use of non-invasive brain stimulation for enhancing neural functions and reducing symptoms in anxiety disorders is growing. Based on the DSM-V classification for anxiety disorders, we examined all available research using repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) for the treatment of specific phobias, social anxiety disorder, panic disorder, agoraphobia, and generalized anxiety disorder. A systematic literature search conducted in PubMed and Google Scholar databases provided 26 results: 12 sham-controlled studies and 15 not sham-controlled studies. With regard to the latter sub-group of studies, 9 were case reports, and 6 open label studies. Overall, our work provides preliminary evidence that both, excitatory stimulation of the left prefrontal cortex and inhibitory stimulation of the right prefrontal cortex can reduce symptom severity in anxiety disorders. The current results are discussed in the light of a model for the treatment for anxiety disorders via non-invasive brain stimulation, which is based on up-/downregulation mechanisms and might serve as guide for future systematic investigations in the field., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Key Points: Nicotine (NIC) modulates cognition and memory function by targeting the nicotinic ACh receptor and releasing different transmitter systems postsynaptically. With both NIC-generated mechanisms, calcium influx and calcium permeability can be regulated, which is a key requirement for the induction of long-term potentiation, comprising the physiological basis of learning and memory function. We attempt to unmask the underlying mechanism of nicotinic effects on anodal transcranial direct current stimulation (tDCS)-induced long-term potentiation-like plasticity based on the hypothesis of calcium-dependency. Abolished tDCS-induced neuroplasticity as a result of NIC administration is reversed by calcium channel blockade with flunarizine in a dose-dependent manner. The results of the present study suggest that there is a dose determination of NIC/NIC agonists in therapeutical settings when treating cognitive dysfunction, which partially explains the heterogeneous results on cognition observed in subjects in different experimental settings., Abstract: Nicotine (NIC) modulates neuroplasticity and improves cognitive performance in animals and humans mainly by increased calcium permeability and modulation of diverse transmitter systems. NIC administration impairs calcium-dependent plasticity induced by non-invasive brain stimulation with transcranial direct current stimulation (tDCS) in non-smoking participants probably as a result of intracellular calcium overflow. To test this hypothesis, we analysed the effect of calcium channel blockade with flunarizine (FLU) on anodal tDCS-induced cortical excitability changes in healthy non-smokers under NIC. We applied anodal tDCS combined with NIC patch and FLU at three different doses (2.5, 5 and 10 mg) or with placebo medication. NIC abolished anodal tDCS-induced neuroplasticity. Under medium dosage (but not under low and high dosage) of FLU combined with NIC, plasticity was re-established. For FLU alone, the lowest dosage weakened long-term potentiation (LTP)-like plasticity, whereas the highest dosage again abolished tDCS-induced plasticity. The medium dosage turned LTP-like plasticity in long-term depression-like plasticity. The results of the present study suggest a key role of calcium influx and calcium levels in nicotinic effects on LTP-like plasticity in humans. This knowledge might be relevant for the development of new therapeutic strategies in cognitive dysfunction., (© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.)

Several techniques and protocols of non-invasive transcranial brain stimulation (NIBS), including transcranial magnetic and electrical stimuli, have been developed in the past decades. Non-invasive transcranial brain stimulation may modulate cortical excitability outlasting the period of non-invasive transcranial brain stimulation itself from several minutes to more than one hour. Quite a few lines of evidence, including pharmacological, physiological and behavioral studies in humans and animals, suggest that the effects of non-invasive transcranial brain stimulation are produced through effects on synaptic plasticity. However, there is still a need for more direct and conclusive evidence. The fragility and variability of the effects are the major challenges that non-invasive transcranial brain stimulation currently faces. A variety of factors, including biological variation, measurement reproducibility and the neuronal state of the stimulated area, which can be affected by factors such as past and present physical activity, may influence the response to non-invasive transcranial brain stimulation. Work is ongoing to test whether the reliability and consistency of non-invasive transcranial brain stimulation can be improved by controlling or monitoring neuronal state and by optimizing the protocol and timing of stimulation., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Low intensity transcranial electrical stimulation (TES) in humans, encompassing transcranial direct current (tDCS), transcutaneous spinal Direct Current Stimulation (tsDCS), transcranial alternating current (tACS), and transcranial random noise (tRNS) stimulation or their combinations, appears to be safe. No serious adverse events (SAEs) have been reported so far in over 18,000 sessions administered to healthy subjects, neurological and psychiatric patients, as summarized here. Moderate adverse events (AEs), as defined by the necessity to intervene, are rare, and include skin burns with tDCS due to suboptimal electrode-skin contact. Very rarely mania or hypomania was induced in patients with depression (11 documented cases), yet a causal relationship is difficult to prove because of the low incidence rate and limited numbers of subjects in controlled trials. Mild AEs (MAEs) include headache and fatigue following stimulation as well as prickling and burning sensations occurring during tDCS at peak-to-baseline intensities of 1-2mA and during tACS at higher peak-to-peak intensities above 2mA. The prevalence of published AEs is different in studies specifically assessing AEs vs. those not assessing them, being higher in the former. AEs are frequently reported by individuals receiving placebo stimulation. The profile of AEs in terms of frequency, magnitude and type is comparable in healthy and clinical populations, and this is also the case for more vulnerable populations, such as children, elderly persons, or pregnant women. Combined interventions (e.g., co-application of drugs, electrophysiological measurements, neuroimaging) were not associated with further safety issues. Safety is established for low-intensity 'conventional' TES defined as <4mA, up to 60min duration per day. Animal studies and modeling evidence indicate that brain injury could occur at predicted current densities in the brain of 6.3-13A/m 2 that are over an order of magnitude above those produced by tDCS in humans. Using AC stimulation fewer AEs were reported compared to DC. In specific paradigms with amplitudes of up to 10mA, frequencies in the kHz range appear to be safe. In this paper we provide structured interviews and recommend their use in future controlled studies, in particular when trying to extend the parameters applied. We also discuss recent regulatory issues, reporting practices and ethical issues. These recommendations achieved consensus in a meeting, which took place in Göttingen, Germany, on September 6-7, 2016 and were refined thereafter by email correspondence., (Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.)

For the past few years, the potential of transcranial direct current stimulation (tDCS) for the treatment of several pathologies has been investigated. In the language domain, several studies, in healthy and brain-damaged populations, have already shown that tDCS is effective in enhancing naming, repetition and semantic word generation. In those studies, different tDCS electrode configurations have been tested, however, a direct comparison between different montages in verbal learning has never been conducted. In this study, we aimed to explore the impact of bihemispheric and unihemispheric tDCS on verbal learning task performance in two groups (young vs. elderly). Fifteen healthy volunteers participated per group. Each participant received three stimulation conditions: unihemispheric anodal tDCS over the left temporal area, bihemispheric tDCS over the left (anodal) and right (cathodal) temporal areas and a sham condition. During active stimulation, tDCS (20min, 2mA) was applied while each participant learned twenty pseudowords (arbitrarily assigned to corresponding pictures). No significant differences were found between the three conditions for the young group with regard to accuracy and vocal reaction times. In contrast, in the elderly group, real stimulation improved performance compared to sham but bihemispheric tDCS was more efficient than unilateral stimulation. These results suggest that bihemispheric stimulation is more effective in improving language learning but this effect is age-dependent. The hypothesis is advanced that cortical changes in the course of aging might differentially impact on tDCS efficacy on behavioral performance. These data may also have implications for treatment of stroke patients with language impairment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Transcranial electrical stimulation (tES), including transcranial direct and alternating current stimulation (tDCS, tACS) are non-invasive brain stimulation techniques increasingly used for modulation of central nervous system excitability in humans. Here we address methodological issues required for tES application. This review covers technical aspects of tES, as well as applications like exploration of brain physiology, modelling approaches, tES in cognitive neurosciences, and interventional approaches. It aims to help the reader to appropriately design and conduct studies involving these brain stimulation techniques, understand limitations and avoid shortcomings, which might hamper the scientific rigor and potential applications in the clinical domain., (Copyright © 2015 International Federation of Clinical Neurophysiology. All rights reserved.)

The field of transcranial electrical stimulation (tES) has experienced significant growth in the past 15 years. One of the tES techniques leading this increased interest is transcranial direct current stimulation (tDCS). Significant research efforts have been devoted to determining the clinical potential of tDCS in humans. Despite the promising results obtained with tDCS in basic and clinical neuroscience, further progress has been impeded by a lack of clarity on international regulatory pathways. Therefore, a group of research and clinician experts on tDCS were convened to review the research and clinical use of tDCS. This report reviews the regulatory status of tDCS and summarizes the results according to research, off-label, and compassionate use of tDCS in the following countries: Australia, Brazil, France, Germany, India, Iran, Italy, Portugal, South Korea, Taiwan, and the US. Research use, off label treatment, and compassionate use of tDCS are employed in most of the countries reviewed in this study. It is critical that a global or local effort is organized to pursue definite evidence to either approve and regulate or restrict the use of tDCS in clinical practice on the basis of adequate randomized controlled treatment trials. [ABSTRACT FROM AUTHOR]

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent “homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols. [ABSTRACT FROM AUTHOR]

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS. [ABSTRACT FROM AUTHOR]

Background Recently, transcranial direct current stimulation (tDCS) became a popular method to non-invasively modulate cerebellar excitability and help us broaden our understanding of cerebellar functions and introduce new therapeutic applications. Despite its popularity, its parameters, such as current polarity, stimulation intensity and electrode positions to induce specific effects have not yet been standardized. We aimed (1) to test the effects of tDCS with different electrode montages (see below) on cerebellar-brain inhibition (CBI) and (2) to explore the effect of tDCS on specific cerebellar-brain connections measured by the CBI recruitment curve (CBI-RC). Methods 15 and 14 young and healthy participants took part in Experiments 1 and 2, respectively. In all experiments, the target tDCS electrode was placed over the right cerebellar cortex. In Exp. 1, the return electrode over one of the following three positions: the right buccinator muscle, the left supraorbital area or the right deltoid muscle and in Exp. 2, it was positioned over the right buccinator muscle. CBI was measured by double-TMS protocol, with the conditioning stimulus (CS) over the right cerebellum with an intensity of 5% below the brainstem motor threshold (BMT) followed by the test pulse over the left primary motor cortex 5 ms later. For CBI-RC, five different CS intensities were used (−5%, −10%, −15%, −20%, −25% below BMT). The after-effects of 2 mA anodal or cathodal cerebellar tDCS on CBI or CBI-RC in Exp. 1 and 2, respectively, were measured before and for two hours after 15 min of tDCS. Results In Exp. 1, both tDCS polarities significantly decreased CBI for at least two hours compared to both sham and pre-stimulation values. No significant differences between different return electrode positions were observed. In Exp. 2, CBI was significantly increased after anodal and was decreased after cathodal tDCS with low CS intensities in a polarity-specific manner. Conclusions In accordance with the results reported by many studies, our results suggest that the return electrode positioning has no significant impact on the tDCS after-effects. The results of Exp. 2 show that the recruitment of the cerebellar-brain connections varies depending on tDCS polarity and CS intensity, suggesting that tDCS differently affects neurons in different layers of the cerebellar cortex. This polarity-specific dependence should be considered for tDCS applications and addressed in future studies. Funded by Mercur Pr-2015-0010 and SFB1280 (TP A05 and A06). [ABSTRACT FROM AUTHOR]

Question Task-specific focal dystonia (TSFD) is typically characterized by involuntary and abnormal muscular cramping, which compromises fine motor control. Previous neurophysiological studies have identified loss of inhibitory control at the motor cortex as a possible pathophysiology of the dystonic cramping. A recent study demonstrated that bi-hemispheric transcranial direct current stimulation (tDCS) over the motor cortices during performing bimanual mirrored finger movements ameliorated impairment of dexterous finger movements in pianists with TSFD. However, little has been uncovered about its underlying neurophysiological mechanism. Here we tested a hypothesis that the bi-hemispheric tDCS with motor retraining normalizes abnormal co-contraction between antagonistic pairs of extrinsic finger muscles in pianists with TSFD. Methods Eight pianists suffering from TSFD at the right hand and eight healthy pianists performed the bimanual mirrored finger movements for twenty-four minutes with two conditions; either with 2 mA tDCS over the motor cortices (cathodal over the left and anodal over the right) for twenty-four minutes (real condition) or thirty seconds (sham condition). Results The results demonstrated changes in pattern of muscular co-contraction only following the real stimulation condition, in which tonic activity turned into more phasic pattern. In addition, the amount of muscular co-contraction was significantly decreased after the real stimulation in the patients, which was the case neither at the sham condition of the patients nor at both conditions of the healthy controls. Conclusions The results provide physiological evidences of restoration of both abnormal pattern and amount of muscular co-activation of musicians’ dystonia through the bi-hemispheric tDCS with bimanual motor retraining. [ABSTRACT FROM AUTHOR]

Premotor cortex activity is associated with complex motor performance and motor learning and offers a potential target to improve dexterity by transcranial direct current stimulation (tDCS). We explored the effects of tDCS of premotor cortex on performance of a Strength-Dexterity test in healthy subjects. METHODS: During the test a slender spring held between thumb and index finger should be compressed as much as possible without buckling. Finger forces assessed in the test provided a measure of dexterity. First, task performance was tested in 12 persons during anodal tDCS to the primary motor cortex (M1) contralateral to the performing hand, and sham stimulation. Another 12 persons participated in five sessions of anodal and cathodal tDCS over the left and the right premotor cortex and sham stimulation. RESULTS: tDCS over M1 as well as over the left, but not the right premotor cortex resulted in significant improvement of performance. Performance alterations correlated positively between left anodal and right cathodal tDCS and negatively between anodal tDCS of the two sides. Effective polarity for premotor stimulation to improve task performance differed between participants. Individuals who improved with anodal stimulation used lower finger force and experienced the test as more difficult compared to those who improved with cathodal stimulation. CONCLUSIONS: This study demonstrates that tDCS over the left premotor cortex can improve performance of a dexterity demanding task. The effective polarity of stimulation depends on the task performance strategies. The study moreover shows a functional relevance of interactions between the left and right premotor cortex. [ABSTRACT FROM AUTHOR]

Question The mechanisms underlying transcranial direct current stimulation (tDCS) induced changes of cortical excitability and arousal remain to be fully characterized. In the context of our larger study on the effects of bifrontal tDCS on overnight sleep, we analyzed tDCS-modulated resting state wake EEG data for a better understanding of tDCS’s effects on cortical arousal during wakefulness. Methods We applied a standardized tDCS protocol (1 mA/electrode, 2 × 9 min cathodal, 2 × 13 min anodal, 2 × 11 min sham, with 20 min inter-stimulation interval each) prior to nighttime sleep bilaterally to the prefrontal cortex (electrodes 5 × 7 cm, FP1/FP2; return electrodes 10 × 10 cm, P3/P4 ) of 19 healthy subjects in a randomized crossover design. We conducted 5 min resting state wake EEGs prior to stimulation (T0), after the stimulation (T1) and on the following morning (T2). In a first step of analysis for EEG power differences between conditions at a single frequency, we calculated false discovery rate (FDR) corrected significances, using the Benjamini-Hochberg step-up procedure to assess the significance of the multiple tests. In a second exploratory step, we used uncorrected ANOVAs to further explore tDCS effects on EEG power spectra. Results The FDR-corrected approach did not reveal any significant condition effect. ANOVAs comparing T1 vs. T0 demonstrated a significant decrease in EEG gamma power after cathodal stimulation. A significant main effect for the factor Condition was observed for frequencies of the gamma range. ANOVAs comparing T2 vs. T0 demonstrated a significant increase in EEG gamma power after anodal stimulation and also a significant main effect for the factor Condition for frequencies of the gamma band. Conclusions Exploratory resting state EEG analyses suggested polarity-specific changes in cortical arousal as indexed by resting state EEG power in the gamma frequency range. Cortical gamma activity is considered to emerge from synchronous activity of fast-spiking inhibitory neurons in the cortex and has been linked to the integration of temporally correlated neural events as a prerequisite for attentive wakefulness. It is plausible that depolarization of cortical structures after anodal stimulation facilitates fast-spiking and EEG gamma activity, with reverse effects after cathodal stimulation. [ABSTRACT FROM AUTHOR]

Question Corticothalamic feedback loops represent a ‘top-down’ pathway of sleep regulation accessible for interventions with non-invasive brain stimulation into sleep physiology. Distinct methods of current stimulation to prefrontal regions can be used to increase slow wave activity, boost memory consolidation, elicit self-awareness during dreams, or alter total sleep time. However, it has not been investigated whether these effects are specific for prefrontal targets or arise from a more general cortical stimulation effect. We hypothesized that parietal transcranial direct current stimulation (tDCS) before sleep is inferior to prefrontal stimulation in modulating total sleep time during overnight sleep. Our aim was to examine whether tDCS effects on sleep regulation are area-specific for prefrontal regions. Methods We applied a standardized tDCS protocol (2 mA, 2 × 9 min. cathodal, 2 × 13 min. anodal) immediately prior to overnight sleep to the parietal cortex of 10 healthy subjects in a randomized crossover design. We compared the results to our initial group, which had undergone the same tDCS protocol to the prefrontal cortex resulting in a significantly reduced total sleep time by 27.6 min after anodal (activating) versus cathodal (deactivating) stimulation ( p < 0.01). Results In contrast to prefrontal stimulation, parietal tDCS prior to overnight sleep did not yield any significant effects on total sleep time and other polysomnographic measures. Conclusions These results strongly support the hypothesis that sleep-modifying effects of tDCS depend on specific corticothalamic feedback loops between the prefrontal cortex and thalamus. We interpret these findings as further evidence for the pivotal role of the prefrontal cortex in regulation of arousal states. Together with our previous data this study supports the assumption that non-invasive brain stimulation to prefrontal areas could be a promising non-pharmaceutical therapeutic approach for conditions of impaired or abundant arousal. [ABSTRACT FROM AUTHOR]

Recent studies exploring the combined effect of motor learning and transcranial direct current stimulation (tDCS) have shown conflicting results. The optimization of the employed training paradigms can be one way to maximize treatment effects. Methods A newly developed visuo-motor force tracking task is directed to the improvement of fine force control in the hand. During the task, a target force is presented on a computer screen and controlled by patients by pressing a power grip force manipulandum with the affected hand. In the present pilot study we investigated motor effects of four-week training with the visuo-motor force tracking task combined with tDCS in 11 chronic stroke patients with different levels of paresis. Anodal (0.5 mA; 5 patients) or sham (6 patients) tDCS was applied on the primary motor cortex (M1) of the lesioned side for 20 min twice a day simultaneously with training.Upper Extremity Fugl-Meyer assessment (FMA; the primary outcome measure) was done before, after and on two months follow-up. Parameters of performance – ramp error, hold error, release duration and mean hold force – were calculated. Results Total UE FMA score was significantly increased immediately after the treatment, but had declined at two months follow-up. The most prominent improvement occurred in the shoulderelbow sub-score of the FMA; in this segment (but not in the total UE FMA score) a significantly greater improvement in the Active compared to the Sham group was observed (Fig. 1 ). A clinically significant improvement (FMA > 5) was revealed in four patients out of five in the Active group and in two out of six – in the Sham group. Hold error decreased significantly in all patients; ramp error – in the Active group. Mean Hold Force during the first treatment session predicted the change in total UE FMA score after treatment (Fig. 2 ). Conclusions The results show that this treatment protocol can result in clinically significant improvement of motor function in chronic stroke patients, including patients with severe paresis. Individual clinical characteristics of the patients could explain heterogeneity of results and lack of difference in the total UE FMA score. Performance during the initial session might inform about clinical outcomes and guide tDCS protocol optimization in future combined treatments. [ABSTRACT FROM AUTHOR]