How long does tdcs last

None of the participants had a history of neurological disease. None were taking centrally acting medication. Neurological examination, including ataxia rating scales 71 , 72 , was performed on the first day of the experiment, and were unremarkable. All participants were naive to eyeblink conditioning and tDCS. Values corresponded to normal age limits in all participants.

The study was approved by the ethics committee of the Essen University Hospital and all methods and experiments were performed in accordance with relevant guidelines and regulations. Oral and written informed consent was obtained from all participants. Delay eyeblink conditioning was performed on four days: day 1, day 2, after one week day 8 , and after one month day 29 Fig.

On day 1, following a pseudoconditioning phase of 10 CS-only and 10 US-only trials presented in pseudorandom order, paired CS—US trials were applied.

On days 2, 8 and 29, 50 paired CS—US trials were applied. This was followed by 30 CS-only extinction trials on day Experimental protocol. At the beginning of day 1, 10 CS-only trials and 10 US-only trials were presented in a pseudorandom sequence pseudo-conditioning , followed by paired CS—US trials. On days 2, 8 1 week and 29 1 month , 50 paired CS—US trials were given. Participants sat comfortably in a chair with both arms resting on armrests. During eyeblink conditioning a silent movie was shown on a screen positioned in front of the participants to maintain vigilance.

Conditioned responses CRs were recorded from orbicularis oculi muscles bilaterally via surface electrodes which were fixed to the lower eyelid and to the nasion.

Signals were fed to EMG amplifiers sampling rate Hz, band pass filter frequency between Hz and 2 kHz , full wave-rectified and further low pass-filtered offline Hz. A standard delay eyeblink conditioning protocol was used according to Gormezano and Kehoe An air-puff duration ms, intensity kPa at source, kPa at nozzle was used as US. The US was directed laterally to the outer canthus of the right eye through a nozzle mounted on a helmet worn by the participants. The CS started ms after onset of each trial, preceded the US onset by a fixed time interval of ms and coterminated with the US.

The intertrial interval varied randomly between 20 and 35 s. Conditioned eyeblink responses were semiautomatically analyzed using a custom made software Responses occurring within the ms interval after CS onset were considered as reflexive responses to the tone alpha-responses and not rated as CRs Trials with spontaneous blinks occurring prior CS onset were excluded from the analysis Rectified EMG recordings were filtered using a series of non-linear Gaussian filters.

CRs were identified when EMG activity reached 7. All trials were visually inspected and implausible identification of CRs was manually corrected. The total number of paired and unpaired extinction trials was subdivided into blocks of 10 trials each.

The number of CRs was expressed as the percentage of trials containing responses with respect to each block of 10 trials percentage CR incidence and the total number of trials total percentage CR incidence.

In addition, CR onset, peak time and area were analyzed. CR onset and peak time were expressed as negative values prior US onset set as 0 ms. CR peak time was defined at the time of maximum amplitude before US onset in paired trials. Mean baseline area was assessed in an interval of ms prior US onset in each trial and subtracted from CR area. CR area was normalized in order to allow comparisons of changes across time.

The frequency of spontaneous blinks was measured on each day within 1 min at the beginning and the end of the experiment. The number of alpha-blinks was assessed. The cerebellar electrode was centered 3 cm lateral to the inion in a vertical position over the right cerebellar hemisphere The return electrode was placed on the ipsilateral buccinator muscle The current of anodal tDCS was set to 2 mA 77 with a ramp-like fade-in and fade-out stimulation of 30 s current density 0.

Stimulation started with the acquisition phase on day one and was performed throughout 50 of the paired CS—US trials Fig. The overall duration of stimulation was 24 min and 12 s including the fade-in and fade-out time. In the sham condition the same fade-in of 30 s was used followed by The modality of stimulation was unknown to the participants as well as to the investigator. Cerebellar tDCS was well tolerated.

Some participants reported a mild tingling at the beginning of the stimulation. First, timing parameters of unconditioned eyeblink responses were analyzed using unpaired t tests. Next, linear mixed model analyses were performed. To assess immediate tDCS effects on CR acquisition learning on day 1, CR incidence was used as dependent variable, block 1—10; 10 blocks of 10 paired trials as within subject factor and stimulation group anodal vs. To assess long-term tDCS effects on CR incidence across days, CR incidence was used as dependent variable, day day 2, day 8, day 29 as within subject factor and stimulation group anodal vs.

To analyze tDCS effects on extinction, CR incidence was used as dependent variable, extinction block 1—3; 10 blocks of 10 extinction CS-only trials as within subject factor and stimulation group anodal vs. Similar mixed model analyses were performed considering CR onset, peak time and area as dependent variable. Nitsche, M. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. Sustained excitability elevations induced by transcranial DC motor cortex stimulation in humans.

Neurology 57 , — Facilitation of implicit motor learning by weak transcranial direct current stimulation of the primary motor cortex in the human. Reis, J. Noninvasive cortical stimulation enhances motor skill acquisition over multiple days through an effect on consolidation. USA , — Liew, S. Non-invasive brain stimulation in neurorehabilitation: Local and distant effects for motor recovery. Front Hum. Grimaldi, G. Cerebellar transcranial direct current stimulation ctDCS : A novel approach to understanding cerebellar function in health and disease.

Neuroscientist 22 , 83—97 Buch, E. Effects of tDCS on motor learning and memory formation: A consensus and critical position paper. Kumari, N. The effect of cerebellar transcranial direct current stimulation on motor learning: A systematic review of randomized controlled trials. Jayaram, G. Modulating locomotor adaptation with cerebellar stimulation. Miterko, L. Consensus paper: Experimental neurostimulation of the cerebellum.

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Aging 35 , — Herzfeld, D. Contributions of the cerebellum and the motor cortex to acquisition and retention of motor memories. Neuroimage 98 , — Das, S. Impairment of long-term plasticity of cerebellar purkinje cells eliminates the effect of anodal direct current stimulation on vestibulo-ocular reflex habituation. Benussi, A. Cerebello-spinal tDCS in ataxia: A randomized, double-blind, sham-controlled, crossover trial.

Neurology 91 , e—e Long term clinical and neurophysiological effects of cerebellar transcranial direct current stimulation in patients with neurodegenerative ataxia. Brain Stimul. Cerebellar transcranial direct current stimulation in patients with ataxia: A double-blind, randomized, sham-controlled study.

Hulst, T. Cerebellar patients do not benefit from cerebellar or M1 transcranial direct current stimulation during force-field reaching adaptation. Jalali, R. No consistent effect of cerebellar transcranial direct current stimulation on visuomotor adaptation. Medina, J. Inhibition of climbing fibres is a signal for the extinction of conditioned eyelid responses. Nature , — Gerwig, M. The involvement of the human cerebellum in eyeblink conditioning.

Cerebellum 6 , 38—57 Timmann, D. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex 46 , — Hesslow, G. Classical conditioning of motor responses: What is the learning mechanism?. Neural Netw. Zuchowski, M. Acquisition of conditioned eyeblink responses is modulated by cerebellar tDCS.

Beyer, L. Cerebellar tDCS effects on conditioned eyeblinks using different electrode placements and stimulation protocols. Technical issues and critical review of the literature. Mamlins, A. No effects of cerebellar transcranial direct current stimulation on force field and visuomotor reach adaptation in young and healthy subjects.

Boneau, C. The interstimulus interval and the latency of the conditioned eyelid response. Prokasy, W. Response shaping at long interstimulus intervals in classical eyelid conditioning. Tran, L. Cerebellar-dependent associative learning is impaired in very preterm born children and young adults.

Limperopoulos, C. Late gestation cerebellar growth is rapid and impeded by premature birth. Pediatrics , — Messerschmidt, A. Disruption of cerebellar development: Potential complication of extreme prematurity. Welsh, J. Cerebellar lesions and the nictitating membrane reflex: Performance deficits of the conditioned and unconditioned response.

Gruart, A. Cerebellar posterior interpositus nucleus as an enhancer of classically conditioned eyelid responses in alert cats.

Delgado-Garcia, J. The role of interpositus nucleus in eyelid conditioned responses. Cerebellum 1 , — Jimenez-Diaz, L. Role of cerebellar interpositus nucleus in the genesis and control of reflex and conditioned eyelid responses. Modulation of cerebellar excitability by polarity-specific noninvasive direct current stimulation. Batsikadze, G. Effects of cerebellar transcranial direct current stimulation on cerebellar-brain inhibition in humans: A systematic evaluation.

Mitroi, J. Polarity- and intensity-independent modulation of timing during delay eyeblink conditioning using cerebellar transcranial direct current stimulation. Cerebellum 19 , — Suppression of cerebellar Purkinje cells during conditioned responses in ferrets. NeuroReport 5 , — Jirenhed, D. Acquisition, extinction, and reacquisition of a cerebellar cortical memory trace. Perrett, S. Cerebellar cortex lesions disrupt learning-dependent timing of conditioned eyelid responses.

A within-subjects design overcomes some of the problems of individual differences in current responsiveness Li et al. However, in terms of the practicality of design, there are issues that must be accounted for, such as the possibility of data being confounded by learning, practice or order effects due to the repeated sessions Berryhill et al.

This can be overcome by counterbalancing the stimulation order across participants or considering practice as a factor in further analyses Li et al. Other issues include subject attrition due to multiple testing sessions, or the potential for unspecified behavioral effects of repeated stimulation. Stimulation over consecutive days can cause cumulative and larger excitability effects Cohen Kadosh et al.

It is also advisable to ensure that participants come back at the same time on all testing days to reduce the risk of circadian influences Krause and Cohen Kadosh, ; Li et al. Between-subject designs have their own pitfalls, such as masking individual differences in performance and susceptibility to tDCS Li et al.

Recent research has demonstrated that anodal and cathodal stimulation do not create reliable changes in cortical excitability across repeated testing sessions within the same individual a potential pitfall of within-subject designs , however an overall increase in excitability was demonstrated at a group level for anodal stimulation.

Sham stimulation was shown to have a stable effect across participants Dyke et al. Additionally a larger sample size is required for between-subjects sub-group analysis. It may therefore be useful to report individual data to further evaluate participant variability within each polarity e. The most common method is indirect, via behavioral measures—i.

The positioning of active electrodes, and the choice of the task including its associated metric , are therefore critical for the observation of tDCS effects. They may, however, be particularly subtle Fregni et al. The task should involve a suitable level of difficulty in order to avoid ceiling or floor effects Fregni et al. Again, this emphasizes the necessary requirement of a sham condition or baseline measure in tDCS experiments.

On the other hand, additional methodologies can be combined with tDCS to provide a more direct means to quantify cerebral changes. Although the focus and scope of this article is not to detail how tDCS is used with these techniques, it is still important to briefly highlight that combining neuroscience techniques may provide a superior picture of brain-behavior relationships. The seminal effects of tDCS were measured through the application of TMS to the motor cortex and recording MEP sizes after different intensities of anodal and cathodal stimulation.

It was shown that cathodal stimulation decreased MEP size from baseline, whilst anodal stimulation had the inverse effect.

Change over time was also measured, showing a gradual return to baseline at approximately the same rate for both polarities highlighting continuing cerebral changes post stimulation Nitsche and Paulus, Recent tDCS-fMRI studies have suggested that stimulation to cortical surface areas may further change the state of networked regions.

For example, Hampstead et al. This may be advantageous when considering the modulation of a network that involves deeper brain regions, however it is important to consider that without the use of fMRI to monitor these effects, the current may flow to areas that are not necessarily predicted by the researcher. Some tDCS machines are fMRI compatible, meaning online tDCS protocols can be carried out during scanning, and without the need for participants to be removed from the scanning room.

Participants can therefore stay in the same position, which is advantageous when voxel placement reproducibility is necessary, or during high-resolution fMRI Woods et al. However, integrating tDCS and fMRI may have a large financial cost, and does have many practical and safety complications.

Meinzer et al. EEG can be used to examine pre- and post-stimulation cortical excitability effects of stimulation, allowing for surrogate markers of tDCS effects to be uncovered Schestatsky et al. Some tDCS studies use the same electrode size for both the target and reference electrodes. This set-up means that if anodal stimulation occurs at the target electrode, an equally strong cathodal current will stimulate the region under the reference electrode.

To address this confounding factor, and to be confident that it is the target region stimulation that alters behavior, current density calculations current strength divided by electrode size can be performed in order to select a reference electrode size that would result in a level of stimulation that will not modulate cortical activity. However, current density at the skin and skull surface is always higher than current density within the brain Wagner et al.

Research has suggested that in order for stimulation to actively modulate cortical activity it should be above a minimum threshold of 0. For example, Knoch et al. It is also assumed that higher current densities translate into stronger effects, although this matter is debated. For example, Bastani and Jaberzadeh illustrated that excitability changes do not necessarily show a linear trend as current density increases. Specifically, 0. This is contradictory to the minimum threshold of 0. These discrepancies in findings may be due to differences in stimulation duration 10 min, in comparison to 5 min and electrode size 24 cm 2 , in comparison to 35 cm 2 across both studies.

When planning a tDCS study, it may be useful to examine papers that have explored different current densities and stimulation parameters. Despite relative consensus on the excitatory effects of anodal stimulation, a recent review has suggested that tDCS experiments that have stimulated non-motor regions have found limited inhibitory effects of cathodal stimulation Jacobson et al. An alternative review paper also concluded that cathodal stimulation does not significantly alter cognitive function Filmer et al.

To add to the ambiguity, it has been proposed that a single session of tDCS regardless of stimulation type has no effect on performance Horvath et al. Overall these differences could be due to the lack of standardized methodologies Li et al. Collectively these reviews emphasize the importance of including all three types of stimulation condition in an experimental design, in order to test for differing and unpredictable results.

Research examining the effect of duration and intensity of stimulation in greater detail has offered some answers, suggesting that the relationship between polarity and enhancement is highly task-dependent. For example, Antal et al. Polarity effects are also dependent on the state of each individual's cortical activity upon arrival for testing, which can be affected by a multitude of factors e. This can cause some participants to show facilitatory anodal effects, and others an inhibitory effect Krause and Cohen Kadosh, Scheduling sessions at the same time each week can help ensure that a participant's routine does not interfere with polarity effects.

These differences may be lost in data after averaging, but still highlight the uncertain nature of how tDCS affects underlying cortices.

Published tDCS research is largely underpowered due to small sample sizes for discussions see: Brunoni et al. Understandably, research on clinical populations may struggle to attain a large and homogenous sample. Small sample sizes can mean that detecting significant tDCS-induced behavioral effects against sham conditions may be difficult and too small to observe, or alternatively if they are significant, they may be spurious Woods et al. Even so, power calculations can inform the appropriate sample size required for the research design.

The homogeneity of a sample can also affect the reliability of results. For example, it has been suggested that anodal stimulation causes a stronger excitability response in women, compared to men Chaieb et al. It would therefore be prudent to consider the relative representation of the sexes during recruitment. However, these increases are usually restorative rather than enhancing, due to age-related cognitive decline Manenti et al. As mentioned previously see Table 1 , many anatomical factors affect tDCS responsiveness, and these factors can change as the brain develops.

Age should therefore be accounted for during analysis or matched as closely as possible between, or within, experimental groups. However, mild temporary side effects may occur, such as headache, a cutaneous sensation at the stimulation sites, moderate fatigue, redness of the skin under the electrode pad, difficulty concentrating, acute mood changes and nausea Poreisz et al.

However, symptoms such as moderate fatigue may be related to participation in an experiment, rather than tDCS itself. The most commonly reported side effect is a cutaneous sensation Poreisz et al.

However, using a small electrode size may be costly for current density, as a lower current may have to be applied if current density becomes too high. To monitor potential side effects, Brunoni et al. We argue that it is advisable to take a measure of the severity of any symptoms, before and after experimentation, as well as including pseudo items i.

A self-report measure prior to tDCS allows the experimenter to apply discretion to judge whether an individual is fit to participate. Rating symptoms after stimulation allows adverse effects associated with tDCS to be reported and for participants to be monitored if experiencing severe symptoms. See Supplementary Material A for an example questionnaire used by our research group. With differences in experimental tasks and aims, exclusion criteria are bound to change.

However, there are some commonalities across studies, and Screening Questionnaires see Supplementary Material B should always be used to assess any risk of participation for each individual recruited.

General exclusion criteria are summarized in Table 2. It should be noted that these criteria are largely based on TMS protocols, and therefore may not all share equal relevance to tDCS paradigms although caution is advised here. The aim of this article is to provide a guide for researchers who are new to the technique, and to highlight some important factors to consider during the design stage of an experiment.

These factors range from recruitment practices and stimulation parameters through to the biology and lifestyle choices of participants. This can make tDCS results unpredictable, and it is therefore advisable to research different designs and thoroughly plan an experiment to control for as many variables as possible. Our current understanding of tDCS and, indeed, this guide may be limited by publication biases, such that experiments producing null results are unavailable for us to learn from.

However, the increasing popularity of tDCS can only lead to a greater array of successful studies that are based on carefully-planned protocols. We hope that the points presented in this article will assist the reader in conducting their own successful tDCS research, and that this will lead to more work that can refine our understanding of the brain-behavior relationships. HT and AH jointly authored the manuscript and prepared it for submission.

RN and AS commented on drafts of the manuscript and contributed additional text. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Gandiga, P. Transcranial DC stimulation tDCS : a tool for double-blind sham-controlled clinical studies in brain stimulation. All the participants received WM training with the load-adaptive verbal N-back task, for 5 days. To examine the training effect, pre- and post-tests were performed, respectively, 1 day before and after the training sessions. At the beginning of each training session, stable-load WM tasks were performed, to examine the performance variation during training.

Compared to the sham stimulation, higher learning rates of performance metrics during the training procedure were found when WM training was combined with active anodal HD-tDCS.

The performance improvements post—pre of the active group, were also found to be higher than those of the sham group and were transferred to a similar untrained WM task. Further analysis revealed a negative relationship between the training improvements and the baseline performance. These findings show the potential that tDCS may be leveraged as an intervention to facilitate WM training, for those in need of a higher WM ability.

Cognitive training, like working memory WM training, has shown the potential to produce broad benefits for those who have special requirements in their cognitive abilities, or for those who suffer from cognitive impairments Richmond et al. As a fundamental and essential cognitive ability, WM supports complex thought but is limited in capacity. Thus, WM training interventions have become popular as a means of potentially improving WM-related cognitive abilities for those in need Au et al.

Transcranial direct current stimulation tDCS , which has shown potential to modulate brain cortical excitability and activity, by transmitting a weak electric current into the brain Andrews et al. Cognitive enhancement, using tDCS, has therefore attracted increased attention over the last decade. In one particularly noteworthy study, carried out by Fregni et al. However, no significant effect appeared when they applied anodal stimulation over the primary motor cortex and cathodal stimulation over the left DLPFC.

These findings indicate that the enhancing effect of tDCS on WM memory depends on the stimulation polarity and is specific to the site of stimulation Fregni et al. Many subsequent studies compared factors like electrode placement, current density and stimulation duration that may affect the efficacy of tDCS and found that the anodal stimulation of the left prefrontal, tended to enhance WM performance Coffman et al.

Hill et al. However, another quantitative review found no evidence of the cognitive effects in healthy populations from single-session tDCS for executive function, language, memory, and miscellaneous tasks Horvath et al. With a more stringent publication bias correction method p-curve Simonsohn et al. This however, does not mean that these reviews can provide definitive evidence for the ineffectiveness of tDCS for cognitive processes.

As Medina and Cason said, the stimulation parameters like stimulation site, polarity, current, reference electrode location, length of stimulation, when stimulation occurred, and other factors varied in the studies they reviewed which may affect the results of the meta-analysis Medina and Cason, Individual differences, like baseline ability, education level and genetic factors, were also found to be important factors that may affect the efficacy of tDCS but has not received sufficient attention Moreno et al.

Another point that should be noted, is that the above reviews mainly focused on studies that utilized tDCS alone in single-session protocols, as an insufficient number of multi-session studies were published before According to the limited number of publications, the WM enhancement potential of tDCS was found to most probably lie in its use during training Mancuso et al.

Based on the assumption that tDCS has the potential to modulate neuronal excitability and synaptic plasticity Hummel and Cohen, ; Santarnecchi et al.

A study in a non-human primate model found that tDCS, coupled with multi-session learning, facilitated associative learning and altered functional connectivity by analyzing the behavioral outcomes and local field potential Krause et al. In a three-session WM training study, implemented in healthy adults, the advantage of WM training combined with a-tDCS was not only presented immediately after the training, but also in the follow-up session up to 9 months after the training Ruf et al.

A-tDCS related benefits maintained stable even as long as a year after the original intervention, in a 7-day tDCS-paired WM training study in young healthy adults Au et al. The enhancement of cortical efficiency and connectivity was also demonstrated in a study which found a significant improvement of WM ability through a-tDCS paired WM training in young healthy adults Jones et al.

Studies in older healthy adults also found that a-tDCS paired WM training induced significantly greater improvements 1 month after the training Jones et al. In the study conducted by Richmond et al.

However, in the study implemented by Ruf et al. In patients with fibromyalgia, a-tDCS paired WM training significantly increased immediate memory when compared to a sham dos Santos et al.

A recent study in monkeys provided evidence that single neuron firing rates and network interactions could be modulated by polarity and a dose of tDCS and higher a-tDCS intensity induced higher firing rates of regular firing neurons Bogaard et al. Although a few reviews questioned the efficacy of tDCS, these recently published studies provide more evidence that WM training paired with tDCS can augment cognition.

Some reports also mentioned that the electrode montage could probably be a factor that influences the efficacy of tDCS and pointed out that the so-called high-definition tDCS HD-tDCS , may more effectively modulate brain functions Horvath et al.

However, The majority of existing studies delivered stimulation using bipolar tDCS BP-tDCS montage with the stimulation electrode over the target brain regions and the return electrode placed elsewhere on or near the head Fregni et al.

A study carried out by Hill et al. Although a few studies explored the effect of tDCS on cognitive training, those studies focused more on the effect of tDCS on cognitive enhancement after training and paid less attention to the variation of cognitive performance during the training procedure. The current study aimed to explore the effect of anodal HD-tDCS on the training procedure, by analyzing the variation of performance of the stable-load task during a multi-session load-adaptive WM training.

A total of 30 college students 18 males; aged 20—25 , without a self-reported history of mental or neurological illness and drug abuse, volunteered to participate in this experiment and provided informed consent.

All participants had normal or corrected to normal vision. All participants were evenly assigned to an active or sham tDCS group, via a simple random assignment. Fifteen participants received active tDCS and the other fifteen received a sham stimulation. There were no differences in age, years of education received or in pretest scores between groups. This study was carried out in accordance with the recommendations of the institutional review board of Tianjin University, the ethics committee of the Academy of Medical Engineering and Translational Medicine at Tianjin University.

All subjects gave written informed consent in accordance with the Declaration of Helsinki. The study protocol was approved by the ethics committee of the Academy of Medical Engineering and Translational Medicine, Tianjin University.

Verbal and shape n-back tasks implemented in PsychoPy Peirce, served as the WM task in this study. Letters in the Arial font in white color, of the 10 consonants B, C, D, F, G, H, J, K, L and M or shapes from the 10 abstract irregular shapes, like the ones shown in Figures 1A,B , were randomly presented in the center of the black background screen which was placed in front of the subjects, respectively, in verbal and shape n-back tasks.

The size of the letters was set to 0. The size of the shapes was similar to the letters. Each trial lasted for 3 s, a letter or a shape was presented for 0. Figure 1. Panels A,B indicate the typical examples for the letters and shapes used respectively in verbal and shape n-back.

Panel C shows the procedure of the whole experiment. Panel D indicates the variation of electric current for the active and sham group during one session. As shown in Figure 1C , every one of the volunteers received seven sessions of experiments on seven consecutive days.

On the next five consecutive days, five WM training sessions followed. Each WM training session consisted of six blocks of verbal n-back tasks, a 3-back, a 4-back and four blocks of load-adaptive n-back tasks. Taking into account the breaks between two consecutive blocks, each training session lasted for about 30 min. The load-adaptive n-back task in this study, means that the load factor n of the current block was adjusted according to the performance of the last block.

Otherwise, the load factor n would be the same with the last block. There was no specified cap on the load factor n , and the maximum that they could reach in the fifth training session depended on the training effect. The post-training test took place the day after the last training session. The tasks in the post-training test were identical to that of the pre-training test session. The reason why the shape 3-back was used in the pre- and post-training sessions, but not in the training sessions, was that the shape 3-back task served as a validation test to examine the training effect and the near-transfer effect.

It should be noted that the five WM training sessions were carried out along with tDCS, while the pre- and post-training test were conducted without tDCS. The settings of sham stimulation helped to mask sham and active conditions. For the pre- and post-training sessions, the changes of these metrics were analyzed to examine the effect of HD-tDCS on training effects, by comparing between active and sham groups.

For the training sessions, the regression lines between the performance metrics and the number of training sessions were regarded as the learning curves. The learning rates the slopes of the learning curves of these metrics were compared between active and sham groups, to examine the effect of HD-tDCS on the training procedure. The changes post—pre and the learning rates were compared between the active and sham groups. One-thousand iterations bootstrapping-based, non-parametric unpaired T -tests were employed as comparisons because a bootstrapping based T -test is distribution-independent and more applicable to small sample sizes than parametric T -tests are Hesterberg et al.

The significance level was corrected with the false discovery rate FDR method Benjamini and Yekutieli, when multiple comparisons were performed. Statistical power analyses were performed with the online tool WebPower 1 for all the comparisons of significance and statistical powers were reported.

Linear regression between the baseline performance metrics and the corresponding learning rates and training gains, were conducted to explore the effect of baseline performance on WM training. The significance level p, the coefficient of determination r 2 and the Pearson correlation coefficient R , were reported for the regression analyses. As shown in Figure 2 , the left panel indicates the learning curves of the mean value of the load factor n that the participants could reach in each training session.

It is obvious that the learning curve of the active group slope: 0. A group-level comparison of the slopes of learning curves of n found significant difference between the active group 0. Figure 2. To further investigate the effect of HD-tDCS, the learning rates of the performance metrics were compared between the active and sham groups, with the bootstrapping based independent sample T -tests. The change rates of the performance metrics, during training, served as learning rates and were obtained by calculating the slopes of linear regressions between the metrics and the number of training sessions.

The results, as shown in Figure 3 , suggest that the active group had apparent higher learning rates than the sham group, for the performance metrics of both verbal 3- and 4-back. Figure 3. The results, as shown in Figure 4 , showed that the gains of the performance metrics of the active group tend to be higher than those of the sham group.