ArticleLiterature Review

Quantitative Review Finds No Evidence of Cognitive Effects in Healthy Populations From Single-session Transcranial Direct Current Stimulation (tDCS)

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Abstract

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. 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. 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. 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. Copyright © 2015 Elsevier Inc. All rights reserved.

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... 23,[35][36][37][38] Further, multiple-session protocols induce larger effects in terms of behavioral changes than do single-session protocols. [38][39][40][41][42] Several studies have adopting 10 or fewer applications, 6 which means that dosing may have been suboptimal for definitive evaluations of its clinical effectiveness. It is notable that recent studies involving relatively large numbers of total sessions over extended periods tended to show morerobust improvements in cognition with more-persistent effects, 38,43,44 relative to trials with smaller numbers of sessions over shorter periods. ...
... It is notable that recent studies involving relatively large numbers of total sessions over extended periods tended to show morerobust improvements in cognition with more-persistent effects, 38,43,44 relative to trials with smaller numbers of sessions over shorter periods. 42,[45][46][47][48] This effect is mirrored through consistent findings across clinical studies, including in our own trials, showing that 1) a single tDCS session does not induce any meaningful behavioral response, 42 and 2) behav- ...
... It is notable that recent studies involving relatively large numbers of total sessions over extended periods tended to show morerobust improvements in cognition with more-persistent effects, 38,43,44 relative to trials with smaller numbers of sessions over shorter periods. 42,[45][46][47][48] This effect is mirrored through consistent findings across clinical studies, including in our own trials, showing that 1) a single tDCS session does not induce any meaningful behavioral response, 42 and 2) behav- ...
Article
Transcranial direct current stimulation (tDCS) is a safe and well-tolerated noninvasive method for stimulating the brain that is rapidly developing into a treatment method for various neurological and psychiatric conditions. In particular, there is growing evidence of a therapeutic role for tDCS in ameliorating or delaying the cognitive decline in Alzheimer's disease (AD). We provide a brief overview of the current development and application status of tDCS as a nonpharmacological therapeutic method for AD and mild cognitive impairment (MCI), summarize the levels of evidence, and identify the improvements needed for clinical applications. We also suggest future directions for large-scale controlled clinical trials of tDCS in AD and MCI, and emphasize the necessity of identifying the mechanistic targets to facilitate clinical applications.
... However, the effects of this technique on risk-taking in people who use substances are unclear, with only one published study showing greater risk-taking behaviors among cannabis users who received anodal stimulation over the left or right dlPFC compared to those who received sham stimulation (Boggio et al., 2010). Other studies conducted among non-users show more inconclusive findings, where some find significant reductions in risk-taking (Pripfl et al., 2013;Gorini et al., 2014;Zheng et al., 2017;Nejati et al., 2018;Khaleghi et al., 2020) while others do not (Minati et al., 2012;Tremblay et al., 2014;Horvath et al., 2015;Lupi et al., 2017;Russo et al., 2017;Guo et al., 2018). ...
... The present finding that tDCS did not significantly affect risktaking behavior is generally consistent with numerous previous studies reporting similar non-significant effects (Minati et al., 2012;Fecteau et al., 2014;Horvath et al., 2015;Ye et al., 2015;Russo et al., 2017;Guo et al., 2018). A recent meta-analysis found a non-significant effect for unilateral (right or left) active tDCS over the dlPFC for risk-taking among healthy adults as compared to sham stimulation (Khaleghi et al., 2020). ...
... In conclusion, we found no significant effects of tDCS over the dlPFC on risk-taking behavior among a sample of adult cannabis users, although we cannot completely rule out the possibility of ceiling effects in the active stimulation group. Our study adds to the growing inconclusive literature on the effects of tDCS on cognition among both healthy controls and substance using samples, particularly for single session tDCS (see quantitative review: Horvath et al., 2015). While tDCS has been shown to be effective for certain psychiatric disorders (i.e., major depressive disorder), it is premature to conclude any beneficial effects of single session tDCS on more complex cognitive processes such as risk-taking, executive functioning, among others. ...
Article
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Individuals with substance use disorders exhibit risk-taking behaviors, potentially leading to negative consequences and difficulty maintaining recovery. Non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) have yielded mixed effects on risk-taking among healthy controls. Given the importance of risk-taking behaviors among substance-using samples, this study aimed to examine the effects of tDCS on risk-taking among a sample of adults using cannabis. Using a double-blind design, 27 cannabis users [ M (SD) age = 32.48 (1.99), 41% female] were randomized, receiving one session of active or sham tDCS over the bilateral dorsolateral prefrontal cortex (dlPFC). Stimulation parameters closely followed prior studies with anodal right dlPFC and cathodal left dlPFC stimulation. Risk-taking—assessed via a modified Cambridge Gambling Task—was measured before and during tDCS. Delay and probability discounting tasks were assessed before and after stimulation. No significant effects of stimulation on risk-taking behavior were found. However, participants chose the less risky option ∼86% of the trials before stimulation which potentially contributed to ceiling effects. These results contradict one prior study showing increased risk-taking among cannabis users following tDCS. There was a significant increase in delay discounting of a $1000 delayed reward during stimulation for the sham group only, but no significant effects for probability discounting. The current study adds to conflicting and inconclusive literature on tDCS and cognition among substance-using samples. In conclusion, results suggest the ineffectiveness of single session dlPFC tDCS using an established stimulation protocol on risk-taking, although ceiling effects at baseline may have also prevented behavior change following tDCS.
... Variance in the effects of tDCS is portrayed by a great cohort of studies that often fail to replicate tDCS effects, thus lowering its reliability and efficacy (Galli, Vadillo, Sirota, Feurra, & Medvedeva, 2019;Hordacre et al., 2017;Horvath, Forte, & Carter, 2015b;Horvath et al., 2016;Tremblay et al., 2016). This threatens the uptake of tDCS in a therapeutic setting (Bestmann & Walsh, 2017;Terranova et al., 2019). ...
... TDCS effects often show low reliability and efficacy, with several studies failing to replicate expected outcomes (Galli et al., 2019;Hordacre et al., 2017;Horvath et al., 2015bHorvath et al., , 2016Tremblay et al., 2016). This calls into question the utility of tDCS as a research tool and limits its therapeutic potential (Bestmann & Walsh, 2017;Terranova et al., 2019). ...
... This effect, however, was not robust enough to reach significance in direct comparison of stimulation conditions. The lack of expected excitability change from both PA-tDCS and HD-tDCS is in line with the notion of low reliability of tDCS effects across studies of tDCS (Horvath et al., 2015b;Huang, Lu, et al., 2017;Ridding & Ziemann, 2010). Several reasons may explain the lack of effect of PA-tDCS and HD-tDCS in these experiments, these include high inter-individual variability, responders losing their effects with individualised-dose tDCS and the short post-tDCS measurements (see next subsections for details). ...
Thesis
The ability of transcranial direct current stimulation (tDCS) to modulate brain activity has vast scientific and therapeutic potential, however, its effects are often variable which limit its utility. Both current flow direction and variance in electric field intensities reaching a cortical target may be vital sources of the variable tDCS effects on neuroplastic change. Controlling for these and exploring the subsequent effects on corticospinal excitability is the aim of this thesis. I here attempted to optimise the delivery of tDCS application by investigating the controlled application of current flow direction and whether through the use of current flow models, we can deliver comparable electric fields with reduced variability across differential montages. To assess whether current flow models are useful, I further investigated if dose-control translates to more consistent physiological outcomes. I demonstrate, firstly, that different current flow directions did not differentially affect the two banks of the central sulcus. Secondly, with the use of dose-control, high-definition tDCS (HD-tDCS) remains focally more advantageous, even with the delivery of comparable electric field intensity and variability as posterior-anterior tDCS (PA-tDCS) to a cortical region. Thirdly, dose-controlled tDCS does not translate to reduced physiological variability. Together, the work presented here suggests that current flow models are useful for informing dose-controlled protocols and montage comparisons for improved tDCS delivery, however, controlling for anatomical differences in the delivery of electric fields to a target is not sufficient to reduce the variability of tDCS effects in physiology. Thus, the methodology for optimised tDCS delivery remains a subject for further improvement and investigation. Advancements in this field may lead to a trusted methodology assisting stroke survivors with a more effective and efficient motor recovery journey.
... Non-invasive brain stimulation (NIBS), which involves sending electrical stimulation through the scalp to target sub-cranial regions (Knotkova et al., 2019;Miniussi et al., 2013), is gaining popularity among scientists, practitioners, and vendors (Simons et al., 2016) as a method to achieve cognitive enhancement. NIBS as a cognitive enhancement method has been investigated in many different populations, ranging from the average healthy layperson (Brunyé et al., 2021;Flöel et al., 2008;Hill et al., 2016;Horvath et al., 2015aHorvath et al., , 2015bMancuso et al., 2016) to military personnel (Brunyé et al., 2020) and clinical populations (Brunyé et al., 2021;Ciullo et al., 2021;Freitas et al., 2011;Hill et al., 2016;Suarez-García et al., 2020). Using NIBS as a cognitive enhancement method is a tantalizing prospect because it is relatively inexpensive, largely safe, and easy to administer (Bikson et al., 2016). ...
... Some studies have found NIBS to be an effective tool for cognitive enhancement (Au et al., 2016;Dockery et al., 2009;Katz et al., 2017;Morales-Quezada et al., 2015;Parasuraman & McKinley, 2014;Richmond et al., 2014;Southworth, 1999;Vodyanyk et al., 2021). Other studies have found detrimental effects (Brunyé et al., 2018;Pyke et al., 2020) or no reliable effects (Horne et al., 2020;Horvath et al., 2015aHorvath et al., , 2015bMancuso et al., 2016;Medina & Cason, 2017;Nilsson et al., 2017;Rabipour et al. 2018bRabipour et al. , 2019Talsma et al., 2017;van Elk et al., 2020). These conflicting findings demonstrate how difficult it is to determine whether NIBS can reliably achieve cognitive enhancement. ...
Article
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There is growing interest in using non-invasive brain stimulation (NIBS) to achieve cognitive enhancement, though success rates have varied across studies. Placebo and placebo-like effects influenced by psychological factors, particularly those related to outcome expectations, could contribute to the mixed findings. In the current Registered Report, we conceptually replicated and extended Rabipour et al.’s (2017) research to understand better how expectations might contribute to cognitive enhancement research results and how individual differences across psychological factors might contribute to such effects. We examined participants’ outcome expectations at two time points: (i) at baseline and (ii) after being primed to have neutral, low (i.e., pessimistic), or high (i.e., optimistic) expectations for NIBS as a cognitive enhancement method. If expectations are malleable, we hypothesized that participants’ expectations would shift toward the prime. Indeed, participants who read the low and high expectation primes reported decreased and increased expectations for cognitive enhancement compared to their baseline expectations, respectively. There were no changes in expectations from baseline to post-prime for participants primed with neutral expectations. These effects held when we accounted for psychological factors like situational motivation as covariates in our analysis. The results from this study could inform methodological considerations for NIBS protocols, including careful controls for unintentionally influencing participants’ perceptions of NIBS effectiveness from recruitment materials, consent forms, and experimenter instructions.
... However, variability across studies was considerable and overall effect size was small. Consequently, different analyses where results are divided into more detailed categories may render meta-analytic findings non-significant (Horvath et al., 2015). ...
... As such, we calculated a brain region specific estimate of tDCS-related WM improvements. Indeed, whereas previous meta-analyses either found small or null effects of tDCS on WM (Brunoni and Vanderhasselt, 2014;Hill et al., 2016;Horvath et al., 2015;Mancuso et al., 2016), our method revealed that a medium effect (7.8 % explained variance), specifically for the lower DLPFC/upper IFC region. In sum, converging evidence of 87 effect sizes, reported in 68 peer-reviewed articles, suggested that anodal tDCS can improve WM performance and that targeting the lower DLPFC may be the best way to achieve this. ...
Article
Altering cortical activity using transcranial direct current stimulation (tDCS) has been shown to improve working memory (WM) performance. Due to large inter-experimental variability in the tDCS montage configuration and strength of induced electric fields, results have been mixed. Here, we present a novel meta-analytic method relating behavioral effect sizes to electric field strength to identify brain regions underlying largest tDCS-induced WM improvement. Simulations on 69 studies targeting left prefrontal cortex showed that tDCS electric field strength in lower dorsolateral prefrontal cortex (Brodmann area 45/47) relates most strongly to improved WM performance. This region explained 7.8 % of variance, equaling a medium effect. A similar region was identified when correlating WM performance and electric field strength of right prefrontal tDCS studies (n = 18). Maximum electric field strength of five previously used tDCS configurations were outside of this location. We thus propose a new tDCS montage which maximizes the tDCS electric field strength in that brain region. Our findings can benefit future tDCS studies that aim to affect WM function.
... Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique for modulating brain activity [1][2][3][4]. However, tDCS effects are often variable [3,[5][6][7][8], limiting its efficacy. TDCS is typically applied using a fixed electrode montage and a fixed dose (e.g. ...
... Note: *p<.05; **p<.01 vectors are extracted, and the angular difference (degrees) between S and EF is calculated across the grey matter surface (6) and averaged within each ROI: M1 BANK , M1 CROWN , S1 BANK , and S1 CROWN (7). ...
Article
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The direction of applied electric current relative to the cortical surface is a key determinant of transcranial direct current stimulation (tDCS) effects. Inter-individual differences in anatomy affect the consistency of current direction at a cortical target, likely leading to inter-individual variability in current direction. However, the degree of this variability remains undetermined. Using current flow modelling (CFM), we quantified the inter-individual variability in tDCS current direction at a cortical target (left primary motor cortex, M1). Three montages targeting M1 using circular electrodes were compared: PA-tDCS directed current perpendicular to the central sulcus in a posterior-anterior direction relative to M1, ML-tDCS directed current parallel to the central sulcus in a medio-lateral direction, and conventional-tDCS applied electrodes over M1 and the contralateral forehead. In 50 healthy brain scans from the Human Connectome Project, we extracted current direction and intensity from the gray matter surface in the sulcal bank (M1BANK) and gyral crown (M1CROWN), and neighbouring primary somatosensory cortex (S1BANK and S1CROWN). Results confirmed substantial inter-individual variability in current direction (50%-150%) across all montages. Radial inward current produced by PA-tDCS was predominantly located in M1BANK, whereas for conventional-tDCS it was clustered in M1CROWN. The predominantly radial inward current in functionally distinct subregions of M1 raises the testable hypothesis that PA-tDCS and conventional-tDCS modulate cortical excitability through different mechanisms. We show that electrode locations can be used to closely approximate current direction in M1 and precentral gyrus, providing a landmark-based method for tDCS application to address the hypothesis without the need for MRI. By contrast, ML-tDCS current was more tangentially oriented, which is associated with little somatic polarization. Substantial inter-individual variability in current direction likely contributes to variable neuromodulation effects reported for these protocols, emphasising the need for individualised electrode montages, including the control of current direction.
... The study of Workman shows that although the current intensity of 2 mA is generally considered to be relatively safe, no side effects are found under the stimulation of 4 mA, and subjects find it tolerable [18]. In addition, individual differences in hair, sebum content, and skull thickness can affect the current intensity, resulting in huge individual differences in the TES intervention effect [19][20][21]. According to Nitsche, the same stimulus intensity can cause long-term stimulation in children but long-term inhibition in adults [22], so the fixed stimulus intensity may be a "rigid choice". ...
... In contrast to the above results, Vöröslakos et al. believe that a higher intensity of current stimulation (4-6 mA) may be needed to obtain enough current passing through the scalp [16,51], subcutaneous tissue, and skull to affect the excitability of nerves in the brain. The differences in the above studies may be caused by the baseline state of the subjects, the thickness of the skull, the density of hair, and the thickness of fat, which is consistent with the results of Horvath [19]. ...
Article
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Previous studies have reported the effect of transcranial pulsed current stimulation (tPCS) on eliminating cognitive fatigue, but there is little research on optimizing the intervention program of tPCS. The purpose of this study was to explore the effect of different tPCS intervention programs on the elimination of physical fatigue in college athletes. Accordingly, 40 healthy college athletes were randomly divided into two groups of 20, denoted as A and B. Both groups exercised on treadmills. There were 15 subjects in group A who met the criteria of moderate physical fatigue, and 15 subjects in group B who met the criteria of severe physical fatigue. The subjects in each group were intervened with five different intervention programs of tPCS (intervention programs Ⅰ, II, III, IV and Ⅴ). The heart rate variability (HRV) and concentrations of oxygenated hemoglobin (HbO2) were measured before and after each intervention to judge the elimination effects of different intervention programs on different degrees of physical fatigue; the measurement indicators of the HRV include RMSSD, SDNN, HF and LF. The results indicated that tPCS intervention can eliminate both moderate and severe physical fatigue. Programs II, III, and IV had a significant effect on eliminating the moderate physical fatigue of athletes (p < 0.05), among which program II, with a stimulation time of 30 min and a stimulation intensity of sensory intensity, had the best effect. Programs I, II, III, and IV all had significant effects on eliminating the severe physical fatigue of athletes (p < 0.05), among which program I, with a stimulation time of 30 min and a stimulation intensity of sensory intensity + 0.2 mA, had the best effect. We conclude that different tPCS intervention programs can have different effects on the elimination of physical fatigue. The effects of the five intervention programs on the elimination of physical fatigue in athletes are as follows: program II is most suitable for moderate physical fatigue, and program I is most suitable for severe physical fatigue.
... Yet, these positive effects of neurostimulation are sometimes debated and challenged by some meta-analyses. Horvath et al. (2015) conducted a meta-analysis on the effects of anodal and cathodal tDCS among normal populations for online (i.e., during tDCS delivery) and offline (i.e., after tDCS had been administered) applications on several aspects including working memory, executive control, and language. Of the 59 analyses they ran, no significant support was found. ...
Article
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Efforts have always been deployed to surpass limitations in human cognitive abilities to enhance aspects such as task accuracy, work effectiveness, and error management. Cognitive enhancement is a field aiming at improving human cognition to overcome those limitations. It bears important interest from the human factors community given its potential for reducing errors in complex operational environments, but also for occupational psychology to improve work performance, mitigate risks, and improve job stress/well-being. Yet, cognitive enhancement strategies are still marginally used in practice. The current narrative review presents a brief summary of the literature on human cognitive enhancement and discusses key implications as well as operational applications of the main methods and technologies reported in this field. Using a human factors perspective, the paper also outlines how such techniques could be integrated into intelligent support systems to help operators facing cognitive challenges in complex operational domains, including those experiencing functional limitations preventing them to contribute to the workforce. We also discuss the implications of integrating such techniques into the workplace and the consequences this might incur for workers and stakeholders. Then, we briefly present a five-step guideline to discuss ways of optimally integrating cognitive enhancement methods into the workplace.
... This evidence suggests that fine-grained methods, such as the present spatiotemporal approach, may reveal subtle, but significant, effects of neuromodulation, not detectable with gross measures such as the analysis of overall reaction time or response accuracy, at least in the healthy population. On the other hand, this could also imply that, under some experimental conditions, or with respect to some cognitive domains, tDCS effects on healthy human performance could be negligible [6]. ...
Article
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Transcranial Direct Current Stimulation (tDCS) has been employed to modulate visuo-spatial attentional asymmetries, however, further investigation is needed to characterize tDCS-associated variability in more ecological settings. In the present research, we tested the effects of offline, anodal conventional tDCS (Experiment 1) and HD-tDCS (Experiment 2) delivered over the posterior parietal cortex (PPC) and Frontal Eye Field (FEF) of the right hemisphere in healthy participants. Attentional asymmetries were measured by means of an eye tracking-based, ecological paradigm, that is, a Free Visual Exploration task of naturalistic pictures. Data were analyzed from a spatiotemporal perspective. In Experiment 1, a pre-post linear mixed model (LMM) indicated a leftward attentional shift after PPC tDCS; this effect was not confirmed when the individual baseline performance was considered. In Experiment 2, FEF HD-tDCS was shown to induce a significant leftward shift of gaze position, which emerged after 6 s of picture exploration and lasted for 200 ms. The present results do not allow us to conclude on a clear efficacy of offline conventional tDCS and HD-tDCS in modulating overt visuospatial attention in an ecological setting. Nonetheless, our findings highlight a complex relationship among stimulated area, focality of stimulation, spatiotemporal aspects of deployment of attention, and the role of individual baseline performance in shaping the effects of tDCS.
... Even though neurophysiological and behavioral effects of tDCS have been demonstrated across a wide range of cognitive and motor functions [14][15][16][17][18], the findings were not always consistent, which raised skepticism about its effectiveness [19,20]. ...
Article
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Transcranial direct current stimulation (tDCS) has become a valuable tool in cognitive neuroscience research as it enables causal inferences about neural underpinnings of cognition. However, studies using tDCS to modulate cognitive functions often yield inconsistent findings. Hence, there is an increasing interest in factors that may moderate the effects, one of which is the participants’ beliefs of the tDCS condition (i.e., real or sham) they received. Namely, whether participants’ correct guessing of sham condition may lead to false-positive tDCS effects. In this study, we aimed to explore if participants’ beliefs about received stimulation type (i.e., the success of blinding) impacted their task performance in tDCS experiments on associative (AM) and working memory (WM). We analyzed data from four within-subject, sham-controlled tDCS memory experiments (N = 83) to check if the correct end-of-study guess of sham condition moderated tDCS effects. We found no evidence that sham guessing moderated post-tDCS memory performance in experiments in which tDCS effects were observed as well as in experiments that showed null effects of tDCS. The results suggest that the correct sham guessing (i.e., placebo-like effect) is unlikely to influence the results in tDCS memory experiments. We discuss the results in light of the growing debate about the relevance and effectiveness of blinding in brain stimulation research.
... Методика БАК разработана и практикуется в только российских клиниках, отсутствуют международные дан-ные о применении метода и его возможностях в детской клинической практике. Об использовании метода ТКМП в странах Европы и в США имеются единичные публикации [47,48]. Несмотря на широкое применение метода Томатиса в детской практике, крупных нерандомизированных международных исследований в этом отношении не проводилось. ...
Article
Speech disorders have the leading position among cognitive disorders and represent the urgent medical problem. The modern approach to the treatment of cognitive and behavioral disorders in children consists of the integrity of pharmacotherapeutic, correctional and psychotherapeutic, as well as non-invasive instrumental methods of brain neurostimulation. This article provides the overview of the currently available data on transcranial magnetic stimulation method as noninvasive treatment of various neuropsychiatric disorders in children and its difference from physiotherapeutic methods used in traditional Russian practice.
... By passing small electrical currents of 1 or 2mA through 'anodal' and 'cathodal' scalp electrodes, tDCS can open sodium-dependent ion channels in 'underlying' neurons (12), increasing intracellular calcium concentration (13,14) and driving long term potentiation (LTP) effects (15). However, despite widespread interest in tDCS and appeal due to its noninvasive (16), inexpensive (17), and easily disseminatable nature (18)(19)(20)(21), there are inconsistent effects of stimulation (22)(23)(24)(25)(26) and no FDA-approved indication for tDCS to date. ...
Preprint
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Transcranial direct current stimulation (tDCS) is a widely used noninvasive brain stimulation technique with mixed results and no FDA-approved therapeutic indication to date. So far, thousands of published tDCS studies have placed large scalp electrodes directly over the intended brain target and delivered the same stimulation intensity to each person. Inconsistent therapeutic results may be due to insufficient cortical activation in some individuals and the inability to determine an optimal dose. Here, we computed 3000 MRI-based electric field models in 200 Human Connectome Project (HCP) participants, finding that the largely unexamined variables of electrode position, size, and between-electrode distance significantly impact the delivered cortical electric field magnitude. At the same scalp stimulation intensity, smaller electrodes surrounding the neural target deliver more than double the on-target cortical electric field while stimulating only a fraction of the off-target brain regions. This new optimized tDCS method can ensure sufficient cortical activation in each person and could produce larger and more consistent behavioral effects in every prospective research and transdiagnostic clinical application of tDCS.
... Changes in GABA post stimulation were not mirrored by changes in working memory behavioural metrics. These results are perhaps not surprising as previous studies in healthy populations have demonstrated no behavioural effects of a single session of atDCS over DLPFC (49,50). It is possible that behavioural changes develop over a longer period or that repeated sessions of atDCS are required for a measurable impact on behavioural outcomes. ...
Preprint
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Background Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates how inter-individual differences in GABA relate to working memory and whether application of anodal transcranial direct current stimulation (atDCS) can modulate of GABA and working memory. Methods 31 adolescents with NF1 were recruited to a single-blind, sham-controlled cross-over trial. Baseline assessments included detailed working memory tests and parent reported measures. Each participant had two study visits, one with atDCS and another with sham intervention applied to the left Dorsolateral Prefrontal Cortex (DLPFC) inside the scanner. Magnetic Resonance Spectroscopy was collected before and after aTDCS/sham intervention in the left DLPFC and occipital cortex. Results Higher baseline GABA was associated with faster response times (RT) on verbal and visuospatial working memory measures. No correlation was observed between baseline GABA and working memory accuracy. AtDCS was associated with significantly greater reduction in GABA, as compared to sham in the left DLPFC. There was no effect of atDCS on Glx in left DLPFC and no significant effect of atDCS on GABA or Glx in the occipital cortex. There was no effect of atDCS on behavioural measures of working memory. Limitations Limitations of this study include use of brief behavioural outcome measures post tDCS chosen to reduce participant burden and the lack of a healthy control group. The GABA levels measured in this study will contain contributions from co-edited macromolecule signal (so-called GABA+), but the relative contribution of these macromolecular signals are thought to be constant unlikely to account for within participant/session GABA changes. Conclusions This first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. This focussed mechanism trial presents a highly promising approach to understanding complex neural pathology in neurodevelopmental disorders. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising novel therapeutic approach. ClinicalTrials.gov Identifier: NCT0499142. Registered 5th August 2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428
... The optimal stimulation of the target ROI was experienced differently across the three subjects: (a) subject 1 was neutral to changes in current dose, and the electric field intensity remained proportional to the injected current; (b) subject 2 had better focality from a dose of 2 mA or more (but not from 1 mA); and (c) subject 3 gained better stimulation from 1 mA compared to 2 or 3 mA of current dose. Such interindividual inconsistency in tDCS due to the current dose has been widely reported in previous studies [17][18][19][56][57][58][59][60][61][62]. With this i-SATA(MNI) framework post-processing the structural scans simulated in ROAST, tDCS users can configure personalized protocols for montage selection (refer to [11,35]) and identify the optimal current dose for cortical targeting (guided by DTDI). ...
Article
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Background: In transcranial direct current stimulation (tDCS), the injected current becomes distributed across the brain areas. The objective is to stimulate the target region of interest (ROI) while minimizing the current in non-target ROIs (the ‘focality’ of tDCS). For this purpose, determining the appropriate current dose for an individual is difficult. Aim: To introduce a dose–target determination index (DTDI) to quantify the focality of tDCS and examine the dose–focality relationship in three different populations. Method: Here, we extended our previous toolbox i-SATA to the MNI reference space. After a tDCS montage is simulated for a current dose, the i-SATA(MNI) computes the average (over voxels) current density for every region in the brain. DTDI is the ratio of the average current density at the target ROI to the ROI with a maximum value (the peak region). Ideally, target ROI should be the peak region, so DTDI shall range from 0 to 1. The higher the value, the better the dose. We estimated the variation of DTDI within and across individuals using T1-weighted brain images of 45 males and females distributed equally across three age groups: (a) young adults (20 ≤ x ˂ 40 years), (b) mid adults (40 ≤ x ˂ 60 years), and (c) older adults (60 ≤ x ˂ 80 years). DTDI’s were evaluated for the frontal montage with electrodes at F3 and the right supraorbital for three current doses of 1 mA, 2 mA, and 3 mA, with the target ROI at the left middle frontal gyrus. Result: As the dose is incremented, DTDI may show (a) increase, (b) decrease, and (c) no change across the individuals depending on the relationship (nonlinear or linear) between the injected tDCS current and the distribution of current density in the target ROI. The nonlinearity is predominant in older adults with a decrease in focality. The decline is stronger in males. Higher current dose at older age can enhance the focality of stimulation. Conclusion: DTDI provides information on which tDCS current dose will optimize the focality of stimulation. The recommended DTDI dose should be prioritized based on the age (>40 years) and sex (especially for males) of an individual. The toolbox i-SATA(MNI) is freely available.
... Consequently, effects of tACS are typically small and it has been suggested that larger amplitudes may have a more robust effect on cognition . However, it should be emphasized that the absence of strong behavioral results does not implicate that electrical brain stimulation is ineffective, as has been suggested by some (Horvath et al., 2015). Whether tACS induces observable behavioral changes depends on having the correct stimulation parameters (location, frequency, intensity), as well as, importantly, a behavioral task that is sufficiently sensitive to actually detect any changes. ...
Article
In decision-making with uncertain outcomes people may rely on external cues, such as expert advice, even if this information has no predictive value. While the fronto-parietal event-related potential (ERP) components feedback-related negativity (FRN) and P3 are associated with both reward/punishment feedback processing, the relationship between ERP modulation and expert advice during decision making remains unclear. In this double-blind sham-controlled within-subject study transcranial alternating current stimulation (tACS) at an intensity of 1 mA was applied to the frontal cortex in twenty-four healthy volunteers. The aim was to decrease reliance on expert advice by targeting FRN, P3a and P3b components. Following administration of frontal delta (2.5 Hz), theta (5 Hz) and sham tACS, ERPs and advice-guided decision making were evaluated. Results showed a tentative behavioral effect of delta tACS in the response bias. In contrast, theta tACS significantly lowered P3b and P3a amplitudes, but no effects of tACS were observed for the FRN. Effects on electrophysiology and advice following behavior were uncorrelated. Our findings suggest that theta tACS may modulate electrocortical signals and delta tACS advice following, yet the relationship between both remains unresolved.
... Neuromodulatory techniques like tDCS often fail to significantly modify behavior (for reviews, see Berryhill et al., 2014;Horvath et al., 2015;Medina & Cason, 2017). Researchers have suggested that numerous procedural differences might explain some of this variability such as the time of stimulation (before/offline or during a task/online), the number of stimulation days, the strength of stimulation, or the site of electrode placements. ...
Article
Transcranial direct current stimulation (tDCS) on the dorsolateral prefrontal cortex (DLPFC) was used to improve foreign-langue learning while using mental imagery. Participants underwent two sessions of 1 mA, 1.5 mA, or sham stimulation prior to learning Swahili-English word pairs two consecutive days. During learning, participants were encouraged to create a mental image of the associated English word. Twenty-four hours after learning and one week later, participants received a cued recall test. A linear dose–response effect of stimulation was found across both tests that occurred long after the immediate effects of stimulation. Follow-up comparisons revealed that only the 1.5 mA condition differed from the sham group. Exploratory moderating effects revealed interactions with sleep quality and handedness. Those with poorer sleep and who were left-handed showed greater recall after 1.5 mA of stimulation than those with better sleep and right-handers. A follow-up behavioral study probing strategy usage indicated that mental imagery strategy use did not strongly impact learning but point to other possible mechanisms including the importance of attending to multimodal perceptual details and memory consolidation. This preliminary evidence supports the role of the DLPFC or connected regions in foreign language vocabulary learning and verbal memory encoding.
... In 2015, Horvath and colleagues conducted two different systematic reviews where they reported no effects of tDCS in healthy population (Horvath et al., 2015a,b). One (Horvath et al., 2015b) analyzed the impact of a single tDCS session on different cognitive measures (executive function, language, memory and others) in healthy adults, and found no significant tDCS effect on any of the cognitive domains selected. However, the positive results obtained in the meta-analysis described here may be due to the stimulation objective, the learning paradigms, and the placement of the electrodes of the reviewed studies. ...
Article
Background: Transcranial electrical stimulation (tES) techniques have been used to enhance different cognitive domains such as language in healthy adults. While several reviews and meta-analysis have been conducted on the effects of tES on different language skills (picture naming, verbal fluency, word reading), there has been little research conducted to date on the effects of tES on the processes involved in foreign language learning. Objective: A meta-analysis was performed to quantify the effects of tES on foreign language learning processes (non-words, artificial grammar, and foreign languages), focusing on accuracy, response times and 1-week follow-up effects, if reported by the studies. Results: Eleven studies that had sham condition were reviewed. Nine of them were analyzed, including five using within-participant design, and four that employed between-participant design. The final analysis encompassed nine studies with 279 healthy participants. The analysis showed moderate enhancing effects of tES on overall language learning (g = 0.50, 95% CI [0.29, 0.71], p = .0001). However, results were not significant on follow up data (g = 0.54, 95% CI [-0.12, 1.20], p = .07), and on response times (g = 0.50, 95% CI [-0.1, 1.18], p = .10). The effects were significantly moderated by years of education. Conclusions: The results suggest that tES seems to enhance the mechanisms involved in foreign language learning; however, more research is needed to understand the impact scope of these techniques on language learning processes.
... Compounding this unreliability are subtle effects and improvements limited to the trained cognitive task, without any transfer of benefit to untrained tasks and therefore no benefit to daily living (Melby-Lervåg et al., 2016;Richmond et al., 2011). Attempts to improve outcomes by augmenting cognitive training with noninvasive neurostimulation have been met with similarly unreliable results (Berryhill et al., 2019;Horvath et al., 2015;Polanía et al., 2018). This problem of unreliability is further compounded by differential methods utilized between research laboratories and the file drawer problem, where only statistically significant results are rewarded with publications and further grants (Medina & Cason, 2017;Melby-Lervåg et al., 2016). ...
... Nevertheless, several studies have found very little or null effects (e.g., Horvath et al., 2015) of tDCS on various cognitive domains. These results have been attributed to high inter-study and inter-individual variability in response to tDCS (Li et al., 2015), even though the sources of inter-individual variability were not clearly identified. ...
... Notably, tDCS is a common intervention technique that has been theorized to alter cortex excitability by applying a low-amplitude electric current through electrodes positioned on the scalp (Fregni & Pascual-Leone, 2007). Further, the focus on headaches from tDCS has validity, as participants undergoing tDCS have reported headaches from the procedure (e.g., Horvath et al., 2015). ...
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Attribute framing presents an ethically sound approach for reducing adverse nocebo effects. In past studies, however, attribute framing has not always decreased nocebo effects. The present study used a sham tDCS procedure to induce nocebo headaches to explore factors that may contribute to the efficacy of attribute framing. Participants (N = 174) were randomized to one of three between-subject conditions: a no-headache instruction (control) condition and two conditions in which headaches were described as either 70% likely (negative framing) to occur or 30% unlikely (positive framing) to occur. Results revealed nocebo headaches in both framing conditions, as compared to the control condition. Attribute framing did not influence headache measures recorded during the sham tDCS task, but positive framing did have a modest influence on one of two headache items completed after the task. Results suggest that attribute framing could have a stronger influence on delayed nocebo effect measures or retrospective symptom reports; a finding that may explain inconsistencies in the existing framing nocebo effect literature. Exploratory analyses also revealed that low negative affect was associated with stronger nocebo and attribute framing effects, although these effects were found on only a few headache measures. It is concluded that researchers should further investigate the influence of attribute framing on nocebo headaches as a function of both timing and emotional factors. Full text version can be found here: https://rdcu.be/cGZRq
... The literature on tES studies is filled with inconsistencies, and there is no definite conclusion on the efficacy of tES interventions in improving cognition (21). From the physiological point of view, the application of tDCS to the brain shifts the resting membrane potential of superficial horizontal intracortical interneurons, which induce changes to spontaneous neuronal excitability (22). ...
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Background Non-invasive brain stimulation methods have been widely utilized in research settings to manipulate and understand the functioning of the human brain. In the last two decades, transcranial electrical stimulation (tES) has opened new doors for treating impairments caused by various neurological disorders. However, tES studies have shown inconsistent results in post-stroke cognitive rehabilitation, and there is no consensus on the effectiveness of tES devices in improving cognitive skills after the onset of stroke. Objectives We aim to systematically investigate the efficacy of tES in improving post-stroke global cognition, attention, working memory, executive functions, visual neglect, and verbal fluency. Furthermore, we aim to provide a pathway to an effective use of stimulation paradigms in future studies. Methods Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed. Randomized controlled trials (RCTs) were systematically searched in four different databases, including Medline, Embase, Pubmed, and PsychInfo. Studies utilizing any tES methods published in English were considered for inclusion. Standardized mean difference (SMD) for each cognitive domain was used as the primary outcome measure. Results The meta-analysis includes 19 studies assessing at least one of the six cognitive domains. Five RCTs studying global cognition, three assessing visual neglect, five evaluating working memory, three assessing attention, and nine studies focusing on aphasia were included for meta-analysis. As informed by the quantitative analysis of the included studies, the results favor the efficacy of tES in acute improvement in aphasic deficits (SMD = 0.34, CI = 0.02–0.67, p = 0.04) and attention deficits (SMD = 0.59, CI = −0.05–1.22, p = 0.07), however, no improvement was observed in any other cognitive domains. Conclusion The results favor the efficacy of tES in an improvement in aphasia and attentive deficits in stroke patients in acute, subacute, and chronic stages. However, the outcome of tES cannot be generalized across cognitive domains. The difference in the stimulation montages and parameters, diverse cognitive batteries, and variable number of training sessions may have contributed to the inconsistency in the outcome. We suggest that in future studies, experimental designs should be further refined, and standardized stimulation protocols should be utilized to better understand the therapeutic effect of stimulation.
... Although quantitative aspects of cognition were not used, we found that active stimulation of tDCS treatment did not significantly affect cognitive function, as measured by total MMSE score. It has been reported that tDCS treatment has no reliable effect on various dimensions of cognitive function (e.g., executive function, language, memory) in the healthy population [37] and showed no cognitive benefits in MDD patients [38]. Considering these results, our findings suggest that tDCS treatment within six weeks may not result in short-term cognitive decline or improvement. ...
Article
Objective: In numerous studies that have addressed transcranial direct current stimulation (tDCS) devices, participants visit the hospital regularly and undergo stimulation directed by health professionals. This method has the advantage of being able to deliver accurate stimuli in a controlled environment, but it does not adopt the merits of tDCS portability and applicability. Thus, it may be necessary to investigate how self-administered tDCS treatment at home affects depression- related symptoms. Methods: In this randomized, single-blinded clinical trial, 58 patients with major depressive disorder were assigned to active and sham tDCS stimulation groups, and treatment responses were evaluated biweekly over six weeks. Both active and sham tDCS treatment group were treated with escitalopram. All participants were instructed the protocol and usage of at-home tDCS device, and self-administered tDCS treatment at their home. Results: The beck-depression inventory score decreased significantly as treatment progressed, and the degree of symptom improvement was significantly higher in the active group than in the sham tDCS group. There were no significant differences between the two groups in other indices, including the Hamilton Depression Scale. Conclusion: These results suggest that patient-administered tDCS treatment might be effective in improving subjective symptoms of depression.
... Furthermore, cathodal tDCS has also not been found to differ from the effects of anodal tDCS in measures of response inhibition , or to produce behavior-enhancing effects under specific circumstances (Schroeder and Plewnia 2016). Moreover, many quantitative reviews have not even included cathodal tDCS in their investigations or did not specify polarity subgroups (Bell and DeWall 2018;Hill et al. 2016;Horvath et al. 2015;Price et al. 2015). ...
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High-definition transcranial direct current stimulation (HD-tDCS) is a relatively focal, novel non-invasive brain stimulation method with the potential to investigate the causal contributions of specific cortical brain regions to language and cognition. Studies with HD-tDCS typically employ a 4 × 1 electrode design with a single central target electrode surrounded by four return electrodes, among which return current intensity is evenly distributed. With cathodal HD-tDCS, neural excitability in the target region is assumed to be reduced, which offers interesting perspectives for neuropsychological research and interventions. This multi-level meta-analysis compiles published studies using cathodal HD-tDCS in 4 × 1 configuration to modulate cognition and behavior. Regarding HD-tDCS, 77 effect sizes were gathered from 11 eligible reports. We extended this database with 52 effect sizes from 11 comparable reports using conventional tDCS with cathodal polarity. We observed no significant overall effect and no moderation by within-study and between-study variables in HD. In the extended analysis, results suggested a non-linear moderation of cathodal tDCS effects by intensity, driven by negative effect sizes at 1.5 mA. However, studies varied tremendously in task parameters, outcomes, and even technical parameters. Interestingly, within-study heterogeneity exceeded between-study heterogeneity in the present sample, and moderators hardly reduced the residual heterogeneity. Across domains and configurations, both positive and negative effect sizes are possible. We discuss the findings in relation to conventional cathodal tDCS and the framework of polarity specificity. Fundamental aspects of cathodal HD-tDCS are still to be addressed in future research.
... However, interestingly, despite the significant functional and structural connection between M1 and cerebellum shown by neuroimaging and transcranial magnetic stimulation (TMS) studies (Bestmann et al. 2004;Jung et al. 2020;Peters et al. 2020;Spampinato et al. 2020), the majority of tDCS studies that targeted these two brain regions utilized single-site stimulation of either of these sites and mainly unilateral to improve related outcomes, such as CSE (Marquez et al. 2015;Dedoncker et al. 2016;Behrangrad et al. 2019), motor control activities, such as balance (Bellebaum and Daum 2007;Kaminski et al. 2016Kaminski et al. , 2017Baharlouei et al. 2020), and motor learning (Karok and Witney 2013;Ammann et al. 2016;Wiltshire and Watkins 2020;Wang et al. 2021), etc. Although some found promising results (Steiner et al. 2016;Saruco et al. 2017Saruco et al. , 2018Poortvliet et al. 2018, Baharlouei et al. 2020), some could not find any significant changes (Horvath et al. 2015;Craig and Doumas 2017;Ehsani et al. 2017;Kaminski et al. 2017;Medina and Cason 2017;Pohjola et al. 2017;Steiner et al. 2020;Wiltshire and Watkins 2020;Wang et al. 2021). ...
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Transcranial direct current stimulation (tDCS) applied to the primary motor cortex (M1), and cerebellum (CB) can change the level of M1 corticospinal excitability (CSE). A randomized double-blinded crossover, the sham-controlled study design was used to investigate the effects of concurrent bilateral anodal tDCS of M1 and CB (concurrent bilateral a-tDCS M1+CB ) on the CSE. Twenty-one healthy participants were recruited in this study. Each participant received anodal-tDCS (a-tDCS) of 2 mA, 20 min in four pseudo-randomized, counterbalanced sessions, separated by at least 7 days (7.11 days ± 0.65). These sessions were bilateral M1 stimulation (bilateral a-tDCS M1 ), bilateral cerebellar stimulation (bilateral a-tDCS CB ), concurrent bilateral a-tDCS M1+CB , and sham stimulation (bilateral a-tDCS Sham ). Transcranial magnetic stimulation (TMS) was delivered over the left M1, and motor evoked potentials (MEPs) of a contralateral hand muscle were recorded before and immediately after the intervention to measure CSE changes. Short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and long interval intracortical inhibition (LICI) were assessed with paired-pulse TMS protocols. Anodal-tDCS significantly increased CSE after concurrent bilateral a-tDCS M1+CB and bilateral a-tDCS CB . Interestingly, CSE was decreased after bilateral a-tDCS M1 . Respective alterations in SICI, LICI, and ICF were seen, including increased SICI and decreased ICF, which indicate the involvement of glutamatergic and GABAergic systems in these effects. These results confirm that the concurrent bilateral a-tDCS M1+CB have a facilitatory effect on CSE, whereas bilateral a-tDCS M1 exert some inhibitory effects. Moreover, the effects of the 2 mA, 20 min a-tDCS on the CB were consistent with its effects on the M1.
... Third, there is ample heterogeneity in results across studies, and this may be at least partially driven by trait-based differences in anxiety. It is worth noting that heterogeneity of tES effects across studies is not unique to its effects on acute stress responses (Brunyé, 2018(Brunyé, , 2020Horvath et al., 2015;Jacobson et al., 2012;López-Alonso et al., 2014). ...
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Cranial electrotherapy stimulation (CES) has a long history in the clinical sciences as a complementary therapy for treating disorders such as insomnia, depression, and anxiety. Research suggests that CES may also prove valuable for altering physiology and behavior in healthy, non-clinical samples, though data are equivocal and show a high risk of bias. The present study used a double-blind, placebo-controlled, crossover design to examine the effects of CES on emotional, physiological, biochemical, and behavioral responses to acute stress. Healthy male participants visited the laboratory for two sessions, one involving active CES administration (20 min at 100 µA and 0.5 Hz) and one involving sham, inactive CES. During each session, participants were placed under stress (threat of torso shock) while performing challenging cognitive tests, and we measured emotional, biochemical (alpha amylase, cortisol), physiological (heart rate, respiration rate, heart rate variability, pupil diameter), and cognitive behavioral (memory, decision-making, spatial orienting) responses. Outcome metrics were compared using repeated measures analysis of variance (ANOVA) and planned comparisons. The stress induction reliably modulated measures of sympathetic adrenal medullary (SAM) activity but not hypothalamic–pituitary–adrenal (HPA) axis activity. Active versus placebo CES did not significantly influence any emotional, biochemical, or physiological outcome measure. Active CES did, however, selectively increase performance on a recognition memory test and degrade performance on a perceptual decision-making test. Overall, we find no compelling evidence that CES reliably modulates the nervous system’s immediate response to acute stress, suggesting its limited utility for sustaining performance in high-stakes domains involving stress exposure.
... Furthermore, studies should nevertheless investigate this question. Finally, controversies exist regarding the effects of tDCS, mostly arising from meta-analyses that find no reliable effects of tDCS on behavior (eg, 73,74 for a review of the key points of controversy). The most notable criticisms raised are the lack of reproducibility of the effects of tDCS and the large interindividual variability, restricting the generalizability of the results. ...
Article
Background and Hypothesis Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. Study Design PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. Study Results Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of −0.46 (95% CI [−0.78; −0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. Conclusions Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.
... Another meta-analysis showed that tDCS promoted cognitive function in patients with schizophrenia (39). Regarding the lack of effects of elevated cognitive function in a meta-analysis of tDCS targeting healthy participants (40), it is possible that the effects of tDCS differ between healthy participants and patients with mood disorders (41). Within the population of patients whose cognitive function has temporarily declined, a group exists in which tDCS might be effective. ...
... Past work has also found difficulty in replicability and a greater likelihood of publication for significant effects (Minarik et al., 2016). In fact, some in the field suggest no effect of tDCS in healthy adults (Horvath et al., 2015), which supports examining the modulation of pain empathy in more vulnerable populations. While 2 mA has demonstrated changes to a variety of cognitive and emotional outcomes in tDCS literature (Coll et al., 2017;Liu et al., 2016;Mondino et al., 2016;Wang et al., 2014), some work has suggested higher intensity levels are necessary in human models (Vöröslakos et al., 2018). ...
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Pain empathy has a number of social benefits, but can be problematic in those who feel the pain of others too much. The current study examined the use of transcranial direct current stimulation (tDCS) as a modifier of pain empathy with the expectation that cathodal stimulation would decrease pain empathy. Anxiety and general empathy were controlled for, given past work demonstrating their impact on pain empathy. Participants were randomized to either active (cathodal; n = 55) or sham tDCS (n = 55) at 2 mA for 20 min while watching videos of painful events and completing a pain empathy simulation questionnaire. Bayesian linear regression analysis indicated no evidence that tDCS condition affected pain empathy. However, there was strong evidence in favor of a positive relationship between anxiety and pain empathy, and extreme evidence between general empathy and pain empathy. The current study examined a montage over the temporoparietal junction though future work should also investigate other areas related to pain empathy such as the anterior cingulate cortex. Results provide evidence of the need for stronger methodological considerations with regard to tDCS including larger sample sizes. Further, the connection between anxiety and pain empathy demonstrates the need for treatments to not only target classic anxiety symptoms, but other factors than may worsen daily functioning.
... As the case for EEG/MEG, previous parietal TMS/TES studies did not always mention the AG as the exact targeted region; for an illustration of this issue, see Table 1 about TES-induced effects in (Klink et al., 2020). Beyond the issues of focality and mechanisms of action, the relevant empirical evidence sought here is that a significant change in behaviour should follow stimulations over the AG, though the reliability of such stimulationinduced effects might be unclear, e.g. for TES see (Horvath et al., 2015). Indeed, inferences about stimulation-related causal effects are not always unequivocal because such causal effects can result from indirect network-induced (remote) effects (Herbscher and Voss, 2020;Hobot et al., 2020). ...
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Here, the functions of the angular gyrus (AG) are evaluated in the light of current evidence from transcranial magnetic/electric stimulation (TMS/TES) and EEG/MEG studies. 65 TMS/TES and 52 EEG/MEG studies were examined in this review. TMS/TES literature points to a causal role in semantic processing, word and number processing, attention and visual search, self-guided movement, memory, and self-processing. EEG/MEG studies reported AG effects at latencies varying between 32 and 800 ms in a wide range of domains, with a high probability to detect an effect at 300–350 ms post-stimulus onset. A three-phase unifying model revolving around the process of sensemaking is then suggested: (1) early AG involvement in defining the current context, within the first 200 ms, with a bias toward the right hemisphere; (2) attention re-orientation and retrieval of relevant information within 200–500 ms; and (3) cross-modal integration at late latencies with a bias toward the left hemisphere. This sensemaking process can favour accuracy (e.g. for word and number processing) or plausibility (e.g. for comprehension and social cognition). Such functions of the AG depend on the status of other connected regions. The much-debated semantic role is also discussed as follows: (1) there is a strong TMS/TES evidence for a causal semantic role, (2) current EEG/MEG evidence is however weak, but (3) the existing arguments against a semantic role for the AG are not strong. Some outstanding questions for future research are proposed. This review recognizes that cracking the role(s) of the AG in cognition is possible only when its exact contributions within the default mode network are teased apart.
... Our results are consistent with previous studies in which only the cognitive speed of the WMT was enhanced after prefrontal tDCS Neural Plasticity stimulation in young healthy volunteers [37][38][39][40][41]. Two metaanalyses also indicated a favorable enhancement of reaction times with small but significant effect sizes in healthy populations as compared to accuracy improvement in patient samples with baseline WM deficits [42,43]. However, null results of tDCS on cognition have also been reported [35,44]. Among the factors that seem to influence the efficacy of tDCS in HY, the increased task load was shown to play an important role [31,32,37,45]. ...
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Many cognitive functions, including working memory, are processed within large-scale brain networks. We targeted the right frontoparietal network (FPN) with one session of transcranial direct current stimulation (tDCS) in an attempt to modulate the cognitive speed of a visual working memory task (WMT) in 27 young healthy subjects using a double-blind crossover design. We further explored the neural underpinnings of induced changes by performing resting-state fMRI prior to and immediately after each stimulation session with the main focus on the interaction between a task-positive FPN and a task-negative default mode network (DMN). Twenty minutes of 2 mA anodal tDCS was superior to sham stimulation in terms of cognitive speed manipulation of a subtask with processing of objects and tools in unconventional views (i.e., the higher cognitive load subtask of the offline WMT). This result was linked to the magnitude of resting-state functional connectivity decreases between the stimulated FPN seed and DMN seeds. We provide the first evidence for the action reappraisal mechanism of object and tool processing. Modulation of cognitive speed of the task by tDCS was reflected by FPN-DMN cross-talk changes.
... However, some interpersonal heterogeneity has been shown (Wiethoff et al., 2014) to vary slightly between regions of the cerebral cortex (Varoli et al., 2018), and the excitatory or inhibitory effects have been found to be electrically important in relation to axonal orientation (Kabakov, Muller, Pascual-Leone, Jensen, & Rotenberg, 2012). Also, some studies reported that the physiological effects of the higher stimulation intensities (2 mA) on cortical excitability are not exactly similar to those of the lower intensities (Batsikadze, Moliadze, Paulus, Kuo, & Nitsche, 2013;Horvath, Forte, & Carter, 2015;Jacobson, Koslowsky, & Lavidor, 2012). ...
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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 and the percentage of stuttered syllables reduced significantly (42% for oral reading, 38% for monologue and 37% for conversation) after the intervention. In addition, a significant difference was found in the Overall Assessment of the Speaker’s Experience of Stuttering questionnaire score in the anodal group after 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.
... However, this conclusion was based on an integrative analysis of studies with mostly small participant samples. In summary, while there is some evidence that tDCS may improve WM training, there are mixed results regarding the effects of single-session tDCS on WM (Horvath et al. 2015). ...
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Working memory (WM) is essential for reasoning, decision making and problem solving. Recently, there has been an increasing effort in improving WM through non-invasive brain stimulation, especially transcranial direct and alternating current stimulation (tDCS/tACS). Studies suggest that tDCS and tACS can modulate WM performance, but large variability in research approaches hinders identification of optimal stimulation protocols and interpretation of study results. Moreover, it is unclear whether tDCS and tACS differentially affect WM. Here, we summarize and compare studies examining the effects of tDCS and tACS on WM performance in healthy adults. Following PRISMA-selection criteria, our systematic review resulted in 43 studies (29 tDCS, 11 tACS, 3 both) with a total of 1826 adult participants. For tDCS, only 4 out of 23 single-session studies reported effects on WM, while 7 out of 9 multi-session experiments showed positive effects on WM training. For tACS, 10 out of 14 studies demonstrated effects on WM, which were frequency dependent and robust for frontoparietal stimulation. Our review revealed no reliable effect of single-session tDCS on WM, but moderate effects of multi-session tDCS and single-session tACS. We discuss implications of these findings and future directions in the emerging research field of non-invasive brain stimulation and WM.
... Most of the studies that used tDCS as an add-on intervention to WMT have been conducted with young adults and have reported that anodal-tDCS (atDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve WM (Fregni et al., 2005;Zaehle et al., 2011). Nonetheless, other studies failed to find such results following a single-tDCS session (Horvath et al., 2015). Although most of the studies so far were performed in a single-tDCS session, the literature suggests a beneficial effect of repeated sessions (Martin et al., 2013). ...
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Background: Transcranial direct current stimulation (tDCS) has been employed to boost working memory training (WMT) effects. Nevertheless, there is limited evidence on the efficacy of this combination in older adults. The present study is aimed to assess the delayed transfer effects of tDCS coupled with WMT in older adults in a 15-day follow-up. We explored if general cognitive ability, age, and educational level predicted the effects. Methods: In this single-center, double-blind randomized sham-controlled experiment, 54 older adults were randomized into three groups: anodal-tDCS (atDCS)CWMT, shamtDCS (stDCS)CWMT, and double-sham. Five sessions of tDCS (2 mA) were applied over the left dorsolateral prefrontal cortex (DLPFC). Far transfer was measured by Raven’s Advanced Progressive Matrices (RAPM), while the near transfer effects were assessed through Digit Span. A frequentist linear mixed model (LMM) was complemented by a Bayesian approach in data analysis. Results: Working memory training improved dual n-back performance in both groups Q17 submitted to this intervention but only the group that received WMTCatDCS displayed a significant improvement from pretest to follow-up in transfer measures of reasoning (RAPM) and short-term memory (forward Digit Span). Near transfer improvements predicted gains in far transfer, demonstrating that the far transfer is due to an improvement in the trained construct of working memory. Age and Vocabulary scores seem to predict the gains in reasoning. However, Bayesian results do not provide substantial evidence to support this claim. Conclusion: This study will help to consolidate the incipient but auspicious field of cognitive training coupled with tDCS in healthy older adults. Our findings demonstrated that atDCS may potentialize WMT by promoting transfer effects in short-term memory and reasoning in older adults, which is observed especially at follow-up.
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The vagus nerve projects to a well-defined neural circuit via the nucleus tractus solitarii (NTS) and its stimulation elicits a wide range of metabolic, neuromodulatory, and behavioral effects. Transcutaneous vagus nerve stimulation (tVNS) has been established as a promising technique to non-invasively alter brain function. However, the precise dynamics elicited by tVNS in humans are still largely unknown. Here, we performed fMRI with concurrent right-sided tVNS (vs. sham) following a randomized cross-over design (N = 40). First, to unravel the temporal profile of tVNS-induced changes in the NTS, we compared fMRI time series to canonical profiles for stimulation ON and OFF cycles. Model comparisons indicated that NTS time series were best fit by block-wise shifts in signal amplitude with stimulation ON and OFF estimates being highly correlated. Therefore, we compared stimulation (ON + OFF) versus baseline phases and found that tVNS increased fMRI BOLD activation in the NTS, but this effect was dependent on sufficient temporal signal-to-noise ratio (tSNR) in the mask. Second, to identify the spatiotemporal evolution of tVNS-induced changes in the brain, we examined lagged co-activation patterns and phase coherence. In contrast to our hypothesis, tVNS did not alter dynamic functional connectivity after correction for multiple comparisons. Third, to establish a positive control for future research, we measured changes in gastric myoelectrical frequency via an electrogastrogram. Again, in contrast to our hypothesis, tVNS induced no changes in gastric frequency. Collectively, our study provides evidence that tVNS can perturb brain signaling in the NTS, but these effects are dependent on tSNR and require precise localization. In light of an absence of acute tVNS-induced effects on dynamic functional connectivity and gastric motility, we discuss which steps are necessary to advance future research on afferent and efferent effects of tVNS.
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Background: Researchers and clinicians have traditionally relied on elastic caps with markings to reposition the transcranial magnetic stimulation (TMS) coil between trains and sessions. Newer neuronavigation technology co-registers the patient's head and structural magnetic resonance imaging (MRI) scan, providing the researcher with real-time feedback about how to adjust the coil to be on-target. However, there has been no head to head comparison of accuracy and precision across treatment sessions. Objective: /Hypothesis: In this two-part study, we compared elastic cap and neuronavigation targeting methodologies on distance, angle, and electric field (E-field) magnitude values. Methods: In 42 participants receiving up to 50 total accelerated rTMS sessions in 5 days, we compared cap and neuronavigation targeting approaches in 3408 distance and 6816 angle measurements. In Experiment 1, TMS administrators saved an on-target neuronavigation location at Beam F3, which served as the landmark for all other measurements. Next, the operators placed the TMS coil based on cap markings or neuronavigation software to measure the distance and angle differences from the on-target sample. In Experiment 2, we saved each XYZ coordinate of the TMS coil from cap and neuronavigation targeting in 12 participants to compare the E-field magnitude differences at the cortical prefrontal target in 1106 cap and neuronavigation models. Results: Cap targeting was significantly off-target for distance, placing the coil an average of 10.66 mm off-target (Standard error of the mean; SEM = 0.19 mm) compared to 0.3 mm (SEM = 0.03 mm) for neuronavigation (p < 0.0001). Cap targeting also significantly deviated for angles off-target, averaging 7.79 roll/pitch degrees (SEM = 1.07°) off-target and 5.99 yaw degrees (SEM = 0.12°) off-target; in comparison, neuronavigation targeting positioned the coil 0.34 roll/pitch degrees (SEM = 0.01°) and 0.22 yaw (SEM = 0.004°) off-target (both p < 0.0001). Further analyses revealed that there were significant inter-operator differences on distance and angle positioning for F3 (all p < 0.05), but not neuronavigation. Lastly, cap targeting resulted in significantly lower E-fields at the intended prefrontal cortical target, with equivalent E-fields as 110.7% motor threshold (MT; range = 58.3-127.4%) stimulation vs. 119.9% MT (range = 115-123.3%) from neuronavigated targeting with 120% MT stimulation applied (p < 0.001). Conclusions: Cap-based targeting is an inherent source of target variability compared to neuronavigation. Additionally, cap-based coil placement is more prone to differences across operators. Off-target coil placement secondary to cap-based measurements results in significantly lower amounts of stimulation reaching the cortical target, with some individuals receiving only 48.6% of the intended on-target E-field. Neuronavigation technology enables more precise and accurate TMS positioning, resulting in the intended stimulation intensities at the targeted cortical level.
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There is considerable individual variability in the reported effectiveness of non-invasive brain stimulation. This variability has often been ascribed to differences in the neuroanatomy and resulting differences in the induced electric field inside the brain. In this study, we addressed the question whether individual differences in the induced electric field can predict the neurophysiological and behavioral consequences of gamma band tACS. In a within-subject experiment, bi-hemispheric gamma band tACS and sham stimulation was applied in alternating blocks to the participants’ superior temporal lobe, while task-evoked auditory brain activity was measured with concurrent functional magnetic resonance imaging (fMRI) and a dichotic listening task. Gamma tACS was applied with different interhemispheric phase lags. In a recent study, we could show that anti-phase tACS (180° interhemispheric phase lag), but not in-phase tACS (0° interhemispheric phase lag), selectively modulates interhemispheric brain connectivity. Using a T1 structural image of each participant’s brain, an individual simulation of the induced electric field was computed. From these simulations, we derived two predictor variables: maximal strength (average of the 10,000 voxels with largest electric field values) and precision of the electric field (spatial correlation between the electric field and the task evoked brain activity during sham stimulation). We found considerable variability in the individual strength and precision of the electric fields. Importantly, the strength of the electric field over the right hemisphere predicted individual differences of tACS induced brain connectivity changes. Moreover, we found in both hemispheres a statistical trend for the effect of electric field strength on tACS induced BOLD signal changes. In contrast, the precision of the electric field did not predict any neurophysiological measure. Further, neither strength, nor precision predicted interhemispheric integration. In conclusion, we found evidence for the dose-response relationship between individual differences in electric fields and tACS induced activity and connectivity changes in concurrent fMRI. However, the fact that this relationship was stronger in the right hemisphere suggests that the relationship between the electric field parameters, neurophysiology, and behavior may be more complex for bi-hemispheric tACS.
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The increasing number and quality of randomized controlled trials (RCTs) employing transcranial direct current stimulation (tDCS) denote the rising awareness of neuroscientific community about its electroceutical potential and opening to include these treatments in the framework of medical therapies under the indications of the international authorities. The purpose of this quantitative review is to estimate the recommendation strength applying the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) criteria and PICO (population, intervention, comparison, outcome) model values for effective tDCS treatments on no-structural diseases, and to provide an estimate of Sham effect for future RCTs. Applying GRADE evaluation pathway, we searched in literature the tDCS-based RCTs in psychophysical diseases displaying a major involvement of brain electrical activity imbalances. Three independent authors agreed on Class 1 RCTs (18 studies) and meta-analyses were carried out using a random-effects model for pathologies sub-selected based on PICO and systemic involvement criteria. The meta-analysis integrated with extensive evidence of negligible side effects and low-cost, easy-to-use procedures, indicated that tDCS treatments for depression and fatigue in Multiple Sclerosis ranked between moderately and highly recommendable. For these interventions we reported the PICO variables, with left vs. right dorsolateral prefrontal target for 30 min/10 days against depression and bilateral somatosensory vs occipital target for 15 min/5 days against MS fatigue. An across-diseases meta-analysis devoted to the Sham effect provided references for power analysis in future tDCS RCTs on these clinical conditions. High-quality indications support tDCS as a promising tool to build electroceutical treatments against diseases involving neurodynamics alterations.
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One of the primary goals in cognitive neuroscience is to understand the neural mechanisms on which cognition is based. Researchers are trying to find how cognitive mechanisms are related to oscillations generated due to brain activity. The research focused on this topic has been considerably aided by developing non-invasive brain stimulation techniques. The dynamics of brain networks and the resultant behavior can be affected by non-invasive brain stimulation techniques, which make their use a focus of interest in many experiments and clinical fields. One essential non-invasive brain stimulation technique is transcranial electrical stimulation (tES), subdivided into transcranial direct and alternating current stimulation. tES has recently become more well-known because of the effective results achieved in treating chronic conditions. In addition, there has been exceptional progress in the interpretation and feasibility of tES techniques. Summarizing the beneficial effects of tES, this article provides an updated depiction of what has been accomplished to date, brief history, and the open questions that need to be addressed in the future. An essential issue in the field of tES is stimulation duration. This review briefly covers the stimulation durations that have been utilized in the field while monitoring the brain using functional-near infrared spectroscopy-based brain imaging.
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Non-invasive brain stimulation (NIBS) techniques have been increasingly used over the dorsolateral prefrontal cortex (DLPFC) to enhance working memory (WM) performance. Notwithstanding, NIBS protocols have shown either small or inconclusive cognitive effects on healthy and neuropsychiatric samples. Therefore, we assessed working memory performance and safety of transcranial direct current stimulation (tDCS), intermittent theta-burst stimulation (iTBS), and both therapies combined vs placebo over the neuronavigated left DLPFC of healthy participants. Twenty-four subjects were included to randomly undergo four sessions of NIBS, once a week: tDCS alone, iTBS alone, combined protocol and placebo. The 2-back task and an adverse effect scale were applied after each NIBS session. Results revealed a significantly faster response for iTBS (b= -21.49, p= 0.04), but not for tDCS and for the interaction tDCS vs. iTBS (b= 13.67, p= 0.26 and b= 40.5, p= 0.20, respectively). No changes were observed for accuracy and no serious adverse effects were found among protocols. Although tolerable, an absence of synergistic effects for the combined protocol was seen. Nonetheless, future trials accessing different outcomes for the combined protocols, as well as studies investigating iTBS over the left DLPFC for cognition and exploring sources of variability for tDCS are encouraged.
Chapter
Although transcranial direct current stimulation (tDCS) is seemingly simple and easy to apply, specific aspects of sound application and design must be taken into consideration to obtain reliable results in clinical and research settings. This chapter provides an overview of methodological, design, and application techniques important for technically sound application of tDCS. Topics covered in this chapter include clinical/research trial design; patient/participant screening practices; electrode selection, preparation, and placement; montage selection; assessment for adverse events/safety; and functional effects monitoring. This chapter is intended to provide: (1) information for education of researchers and clinicians new to tDCS, (2) a description of methodological details important for experienced tDCS researchers and clinicians attempting to replicate clinical and research outcomes, and (3) highlight methodological details important for consideration in clinical and research applications of tDCS.
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Over the past two decades, the postulated modulatory effects of transcranial direct current stimulation (tDCS) on the human brain have been extensively investigated. However, recent concerns on reliability of tDCS effects have been raised, principally due to reduced replicability and to interindividual variability in response to tDCS. These inconsistencies are likely due to the interplay between the level of induced cortical excitability and unaccounted structural and state-dependent functional factors. On these grounds, we aimed at verifying whether the behavioural effects induced by a common tDCS montage (F3-rSOA) were influenced by the participants’ arousal levels, as part of a broader mechanism of state-dependency. Pupillary dynamics were recorded during an auditory oddball task while applying either a sham or real tDCS. The tDCS effects were evaluated as a function of subjective and physiological arousal predictors (STAI-Y State scores and pre-stimulus pupil size, respectively). We showed that prefrontal tDCS hindered task learning effects on response speed such that performance improvement occurred during sham, but not real stimulation. Moreover, both subjective and physiological arousal predictors significantly explained performance during real tDCS, with interaction effects showing performance improvement only with moderate arousal levels; likewise, pupil response was affected by real tDCS according to the ongoing levels of arousal, with reduced dilation during higher arousal trials. These findings highlight the potential role of arousal in shaping the neuromodulatory outcome, thus emphasizing a more careful interpretation of null or negative results while also encouraging more individually tailored tDCS applications based on arousal levels, especially in clinical populations.
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The development of technologies for brain stimulation provides a means for scientists and clinicians to directly actuate the brain and nervous system. Brain stimulation has shown intriguing potential in terms of modifying particular symptom clusters in patients and behavioral characteristics of subjects. The stage is thus set for optimization of these techniques and the pursuit of more nuanced stimulation objectives, including the modification of complex cognitive functions such as memory and attention. Control theory and engineering will play a key role in the development of these methods, guiding computational and algorithmic strategies for stimulation. In particular, realizing this goal will require new development of frameworks that allow for controlling not only brain activity, but also latent dynamics that underlie neural computation and information processing. In the current opinion, we review recent progress in brain stimulation and outline challenges and potential research pathways associated with exogenous control of cognitive function.
Chapter
Deep brain stimulation (DBS) is just one of many ways to modulate brain circuits. Noninvasive brain stimulation tools, such as transcranial magnetic stimulation and transcranial direct current stimulation may provide insights that are relevant for understanding and improving DBS outcomes. These different brain stimulation modalities target different brain regions in different ways, but might converge on common brain circuits. Connectomics can be used to identify these brain circuits, link different brain stimulation modalities to one another, and allow insights from one stimulation modality to translate into improvements in another.
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Neurofibromatosis 1 (NF1) is a single-gene disorder associated with cognitive phenotypes common to neurodevelopmental conditions such as Autism Spectrum Disorder (ASD) & Attention Deficit Hyperactivity Disorder (ADHD). GABAergic dysregulation underlies working memory impairments seen in NF1. This mechanistic experimental study investigates whether application of anodal transcranial direct current stimulation (atDCS) can modulate GABA and working memory in NF1. 31 adolescents with NF1 were recruited to this single-blind sham-controlled cross-over randomized trial. Active or sham tDCS was applied to the left Dorsolateral Prefrontal Cortex (DLPFC) and Magnetic Resonance Spectroscopy was collected before and after intervention in the left DLPFC and occipital cortex. Higher baseline GABA in the left DLPFC was associated with faster response times (RT) on baseline working memory measures. AtDCS was seen to significantly reduced GABA as compared to sham stimulation in the left DLPFC. There was no effect of atDCS on Glutamate/glutamine (Glx) in the left DLPFC or on GABA/Glx in the occipital cortex. This first such study in adolescents with NF1, showed that atDCS modulates inhibitory activity in the DLPFC. Given the strong evidence linking GABA abnormalities to cognitive deficits across neurodevelopmental conditions such as ASD, modulation of GABA using atDCS offers a promising therapeutic approach. ClinicalTrials.gov Identifier: NCT0499142. Registered 05/08/2021; retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04991428
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Evidence suggests that the visual evoked potential (VEP) and gamma oscillations elicited by visual stimuli reflect the balance of excitatory and inhibitory (E-I) cortical processes. As tDCS has been shown to modulate E–I balance, the current study investigated whether amplitudes of VEP components (N1 and P2) and peak gamma frequency are modulated by transcranial direct current stimulation (tDCS). Healthy adults underwent two electroencephalography (EEG) recordings while viewing stimuli designed to elicit a robust visual response. Between the two recordings, participants were randomly assigned to three tDCS conditions (anodal-, cathodal-, and sham-tDCS) or received no-tDCS. tDCS electrodes were placed over the occipital cortex (Oz) and the left cheek with an intensity of 2 mA for 10 min. Data of 39 participants were analysed for VEP amplitudes and peak gamma frequency using mixed-model ANOVAs. The results showed no main effects of tDCS in any metric. Possible explanations for the absence of tDCS effects are discussed.
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Transcranial direct current stimulation (tDCS) is a noninvasive form of electrical brain stimulation popularly used to augment the effects of working memory (WM) training. Although success has been mixed, some studies report enhancements in WM performance persisting days, weeks, or even months that are actually more reminiscent of consolidation effects typically observed in the long-term memory (LTM) domain, rather than WM improvements per se. Although tDCS has been often reported to enhance both WM and LTM, these effects have never been directly compared within the same study. However, given their considerable neural and behavioral overlap, this is a timely comparison to make. This study reports results from a multisession intervention in older adults comparing active and sham tDCS over the left dorsolateral pFC during training on both an n-back WM task and a word learning LTM task. We found strong and robust effects on LTM, but mixed effects on WM that only emerged for those with lower baseline ability. Importantly, mediation analyses showed an indirect effect of tDCS on WM that was mediated by improvements in consolidation. We conclude that tDCS over the left dorsolateral pFC can be used as an effective intervention to foster long-term learning and memory consolidation in aging, which can manifest in performance improvements across multiple memory domains.
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Transcranial direct current stimulation (tDCS) is a possible alternative to psychostimulants in Attention-Deficit/Hyperactivity Disorder (ADHD), but its mechanisms of action in children and adolescents with ADHD are poorly understood. We conducted the first 15-session, sham-controlled study of anodal tDCS over right inferior frontal cortex (rIFC) combined with cognitive training (CT) in 50 children/adolescents with ADHD. We investigated the mechanisms of action on resting and Go/No-Go Task-based QEEG measures in a subgroup of 23 participants with ADHD (n, sham=10; anodal tDCS=13). We failed to find a significant sham versus anodal tDCS group differences in QEEG spectral power during rest and Go/No-Go Task performance, a correlation between QEEG and Go/No-Go Task performance, and changes in clinical and cognitive measures. These findings extend the non-significant clinical and cognitive effects in our sample of 50 children/adolescents with ADHD. Given that the subgroup of 23 participants would have been underpowered, the interpretation of our findings is limited and should be used as a foundation for future investigations. Larger, adequately powered randomised controlled trials should explore different protocols titrated to the individual and using comprehensive measures to assess cognitive, clinical, and neural effects of tDCS and its underlying mechanisms of action in ADHD.
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Objective ranscranial direct current stimulation (tDCS) is a non-invasive neuro-modulation technique that delivers current through the scalp by a pair of patch electrodes (2-Patch). This study proposes a new multi-channel tDCS (mc-tDCS) optimization method, the distributed constrained maximum intensity (D-CMI) approach. For targeting the P20/N20 somatosensory source at Brodmann area 3b, an integrated combined magnetoencephalography (MEG) and electroencephalography (EEG) source analysis is used with individualized skull conductivity calibrated realistic head modeling. Methods Simulated electric fields (EF) for our new D-CMI method and the already known maximum intensity (MI), alternating direction method of multipliers (ADMM) and 2-Patch methods were produced and compared for the individualized P20/N20 somatosensory target for 10 subjects. Results D-CMI and MI showed highest intensities parallel to the P20/N20 target compared to ADMM and 2-Patch, with ADMM achieving highest focality. D-CMI showed a slight reduction in intensity compared to MI while reducing side effects and skin level sensations by current distribution over multiple stimulation electrodes. Conclusion Individualized D-CMI montages are preferred for our follow up somatosensory experiment to provide a good balance between high current intensities at the target and reduced side effects and skin sensations. Significance An integrated combined MEG and EEG source analysis with D-CMI montages for mc-tDCS stimulation potentially can improve control, reproducibility and reduce sensitivity differences between sham and real stimulations.
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Last year, a widely publicized report by Case Western researchers suggested the cancer drug Targretin could be useful for treating AD. Now, studies by four independent academic teams have failed to replicate some aspects of the original work, but the main conclusions—that Targretin reduces levels of soluble β-amyloid and improves cognitive function in mice—appear to stand.
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For music and language processing, memory for relative pitches is highly important. Functional imaging studies have shown activation of a complex neural system for pitch memory. One region that has been shown to be causally involved in the process for nonmusicians is the supramarginal gyrus (SMG). The present study aims at replicating this finding and at further examining the role of the SMG for pitch memory in musicians. Nonmusicians and musicians received cathodal transcranial direct current stimulation (tDCS) over the left SMG, right SMG, or sham stimulation, while completing a pitch recognition, pitch recall, and visual memory task. Cathodal tDCS over the left SMG led to a significant decrease in performance on both pitch memory tasks in nonmusicians. In musicians, cathodal stimulation over the left SMG had no effect, but stimulation over the right SMG impaired performance on the recognition task only. Furthermore, the results show a more pronounced deterioration effect for longer pitch sequences indicating that the SMG is involved in maintaining higher memory load. No stimulation effect was found in both groups on the visual control task. These findings provide evidence for a causal distinction of the left and right SMG function in musicians and nonmusicians.
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Studies attempting to increase working memory (WM) capacity show promise in enhancing related cognitive functions but have also raised criticism in the broader scientific community given the inconsistent findings produced by these studies. Transcranial direct current stimulation (tDCS) has been shown to enhance WM performance in a single session [Fregni, F., Boggio, P., Nitsche, M., Bermpohl, F., Anatal, A., Feredoes, E., et al. Anodal transcranial direct current stimulation of prefrontal cortex enhances working memory. Experimental Brain Research, 166, 23-30, 2005]; however, the extent to which tDCS might enhance learning on a WM training regime and the extent to which learning gains might transfer outside the training task remains largely unknown. To this end, participants engaged in an adaptive WM training task [previously utilized in Richmond, L., Morrison, A., Chein, J., & Olson, I. Working memory training and transfer in older adults. Psychology & Aging, 26, 813-822, 2011; Chein, J., & Morrison, A. Expanding the mind's workspace: Training and transfer effects with a complex working memory span task. Psychonomic Bulletin & Review, 17, 193-199, 2010] for 10 sessions over 2 weeks, concurrent with either active or sham stimulation of dorsolateral pFC. Before and after training, a battery of tests tapping domains known to relate to WM abilities was administered. Results show that tDCS enhanced learning on the verbal portion of the training task by 3.65 items. Furthermore, tDCS was shown to enhance near transfer to other untrained WM tasks in comparison with a no-contact control group. These results lend support to the idea that tDCS might bolster training and transfer gains in populations with compromised WM abilities.
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Previous research has accumulated convincing evidence to show that the human cerebellum contributes to the short-term storage of verbal information, but its specific role in brain networks involved in phonological storage remains uncertain. In a randomized, crossover and sham-controlled design, we here combined transcranial direct current stimulation (tDCS), applied to the right cerebellum, with fMRI to investigate systematically the contribution of the human cerebellum to encoding, maintenance, and retrieval of verbal information. After anodal, but not cathodal, tDCS, we found a reduced item recognition capacity together with an attenuated neural signal from the right cerebellar lobule VIIb, specifically during the late encoding phase. Within this phase, tDCS furthermore affected task-associated functional connections between right cerebellar lobule VIIb and the posterior parietal cortex. These findings suggest that the right cerebellar lobule VIIb interacts with the posterior parietal cortex, specifically during the late stages of verbal encoding, when verbal information enters phonological storage.
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Currently influential models of working memory posit that memory content is highly accessible to conscious inspection. These models predict that metacognition of memory performance should go hand-in-hand with the accuracy of the underlying memory representation. To test this view, we investigated how visual information presented during the maintenance period affects VSTM accuracy and confidence. We used a delayed cue-target orientation discrimination task in which participants were asked to hold in memory a grating, and during the maintenance period a second memory cue could be presented. VSTM accuracy of the first memory cue was impaired when the orientation of the second memory cue was sufficiently different. However, participants' response confidence was reduced whenever the second memory cue was presented; thus VSTM accuracy and confidence were dissociated. In a second experiment, we applied transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (DLPFC) to investigate the causal role of this region in VSTM metacognition. Relative to the sham condition, anodal tDCS induced a general reduction in confidence ratings but did not affect VSTM accuracy. Overall, these results indicate that our metacognition of memory performance is influenced by factors other than the accuracy of the underlying memory representation.
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Adaptive human behavior depends on the capacity to adjust cognitive processing after an error. Here we show that transcranial direct current stimulation of medial-frontal cortex provides causal control over the electrophysiological responses of the human brain to errors and feedback. Using one direction of current flow, we eliminated performance-monitoring activity, reduced behavioral adjustments after an error, and slowed learning. By reversing the current flow in the same subjects, we enhanced performance-monitoring activity, increased behavioral adjustments after an error, and sped learning. These beneficial effects fundamentally improved cognition for nearly 5 h after 20 min of noninvasive stimulation. The stimulation selectively influenced the potentials indexing error and feedback processing without changing potentials indexing mechanisms of perceptual or response processing. Our findings demonstrate that the functioning of mechanisms of cognitive control and learning can be up- or down-regulated using noninvasive stimulation of medial-frontal cortex in the human brain.
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Human memory is dynamic and flexible but is also susceptible to distortions arising from adaptive as well as pathological processes. Both accurate and false memory formation require executive control that is critically mediated by the left prefrontal cortex (PFC). Transcranial direct current stimulation (tDCS) enables noninvasive modulation of cortical activity and associated behavior. The present study reports that tDCS applied to the left dorsolateral PFC (dlPFC) shaped accuracy of episodic memory via polaritiy-specific modulation of false recognition. When applied during encoding of pictures, anodal tDCS increased whereas cathodal stimulation reduced the number of false alarms to lure pictures in subsequent recognition memory testing. These data suggest that the enhancement of excitability in the dlPFC by anodal tDCS can be associated with blurred detail memory. In contrast, activity-reducing cathodal tDCS apparently acted as a noise filter inhibiting the development of imprecise memory traces and reducing the false memory rate. Consistently, the largest effect was found in the most active condition (i.e., for stimuli cued to be remembered). This first evidence for a polarity-specific, activity-dependent effect of tDCS on false memory opens new vistas for the understanding and potential treatment of disturbed memory control.
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Evidence suggests that excitatory transcranial direct current stimulation (tDCS) may improve performance on a wide variety of cognitive tasks. Due to the non-invasive and inexpensive nature of the method, harnessing its potential could be particularly useful for the treatment of neuropsychiatric illnesses involving cognitive dysfunction. However, questions remain regarding the efficacious stimulation parameters. Here, using a double-blind between-subjects design, we explored whether 1 mA excitatory (anodal) left dorsolateral prefrontal cortex stimulation with a contralateral extracephalic reference electrode, leads to enhanced working memory performance across two days, relative to sham stimulation. Participants performed the 3-back, a test of working memory, at baseline, and during and immediately following stimulation on two days, separated by 24-48 hours. Active stimulation did not significantly enhance performance versus sham over the course of the experiment. However, exploratory comparisons did reveal a significant effect of stimulation group on performance during the first stimulation phase only, with active stimulation recipients performing better than sham. While these results do not support the hypothesis that dorsolateral prefrontal cortex tDCS boosts working memory, they raise the possibility that its effects may be greatest during early learning stages.
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Repeated visual processing of an unfamiliar face suppresses neural activity in face-specific areas of the occipito-temporal cortex. This "repetition suppression" (RS) is a primitive mechanism involved in learning of unfamiliar faces, which can be detected through amplitude reduction of the N170 event-related potential (ERP). The dorsolateral prefrontal cortex (DLPFC) exerts top-down influence on early visual processing. However, its contribution to N170 RS and learning of unfamiliar faces remains unclear. Transcranial direct current stimulation (tDCS) transiently increases or decreases cortical excitability, as a function of polarity. We hypothesized that DLPFC excitability modulation by tDCS would cause polarity-dependent modulations of N170 RS during encoding of unfamiliar faces. tDCS-induced N170 RS enhancement would improve long-term recognition reaction time (RT) and/or accuracy rates, whereas N170 RS impairment would compromise recognition ability. Participants underwent three tDCS conditions in random order at ∼72 hour intervals: right anodal/left cathodal, right cathodal/left anodal and sham. Immediately following tDCS conditions, an EEG was recorded during encoding of unfamiliar faces for assessment of P100 and N170 visual ERPs. The P3a component was analyzed to detect prefrontal function modulation. Recognition tasks were administered ∼72 hours following encoding. Results indicate the right anodal/left cathodal condition facilitated N170 RS and induced larger P3a amplitudes, leading to faster recognition RT. Conversely, the right cathodal/left anodal condition caused N170 amplitude and RTs to increase, and a delay in P3a latency. These data demonstrate that DLPFC excitability modulation can influence early visual encoding of unfamiliar faces, highlighting the importance of DLPFC in basic learning mechanisms.
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[Purpose] This study examined whether transcranial direct current stimulation (tDCS) of both the pre-supplementary motor area (pre-SMA) and primary sensoriomotor cortex (M1) alters the response time in response inhibition using the stop-signal task (SST). [Methods] Forty healthy subjects were enrolled in this study. The subjects were randomly tested under the three: the pre-SMA tDCS, M1 tDCS, and Sham tDCS conditions. All subjects performed a SST in two consecutive phases: without or after the delivery of anodal tDCS over one of the target sites (pre-SMA or the M1) and under the Sham tDCS condition. [Results] Our findings demonstrated significant reductions in the stop processing times after the anodal tDCS over pre-SMA, and change response times were significantly greater under the pre-SMA tDCS condition compared to both the M1 tDCS condition and the Sham tDCS condition. There was no significant major effect after delivery of the tDCS for the go processing times observed among the three conditions. [Conclusion] Anodal tDCS of the pre-SMA or M1 during performance of the SST resulted in enhancement of the volitional stop movement in inhibitory control. Our results suggest that when concurrently applied with the SST, tDCS might be a useful adjuvant therapeutic modality for modulation of the response inhibition and its related dynamic behavioral changes between motor execution and suppression.
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Previous studies have led to hypothesizing that right DLPFC activity is related to risk propensity, but the generality of this relationship remains unclear. Here, we experimentally modulated DLPFC activity in 47 healthy, female volunteers during a risky decision-making task, where monetary gambles defined by potential win, loss, and outcome probability were evaluated in the absence of feedback and uncertainty. Three participant groups, receiving left anodal/right cathodal, right anodal/left cathodal, and sham tDCS, were compared. Overall, participants performed the task well above chance level and were significantly risk averse, but tDCS did not affect task performance or risk propensity. However, right anodal/left cathodal tDCS significantly elevated response confidence, independently of accept/reject response. Our results suggest that the relationship between DLPFC activity and risk propensity may not be universally valid for all task types and requires further characterization. Enhancing right and attenuating left DLPFC activity boosts subjective confidence, with potential implications for understanding pathological gambling.
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To investigate the effects of transcranial direct current stimulation (tDCS) applied over the prefrontal cortex on the improvement of verbal, visuospatial working memory and naming in healthy adults. Thirty two healthy adults (15 males and 17 females, mean age 37.3±13.0 years) were enrolled in this study. The subjects were divided into four groups randomly. They underwent sham or anodal tDCS over the left or right prefrontal cortex, for 20 minutes at a direct current of 1 mA. Before and immediately after tDCS, the subjects performed the Korean version of the mini-mental state exam (K-MMSE) and stroop test (color/word/interference) for the screening of cognitive function. For working memory and language evaluation, the digit span test (forward/backward), the visuospatial attention test in computer assisted cognitive program (CogPack®) and the Korean-Boston Naming Test (K-BNT) were assessed before tDCS, immediately after tDCS, and 2 weeks after tDCS. The stroop test (word/interference), backward digit span test and K-BNT were improved in the left prefrontal tDCS group compared with that of the sham group (p<0.05). The stroop test (interference) and visuospatial attention test were in the right prefrontal tDCS group compared with that of the sham group (p<0.05). Their improvement lasted for 2 weeks after stimulation. tDCS can induce verbal working memory improvement and naming facilitation by stimulating the left prefrontal cortex. It can also improve the visuospatial working memory by stimulating the right prefrontal cortex. Further studies which are lesion and symptom specific tDCS treatment for rehabilitation of stroke can be carried out.
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Previous studies have demonstrated that transcranial direct current stimulation (tDCS) can be proficiently used to modulate attentional and cognitive functions. For instance, in the language domain there is evidence that tDCS can fasten picture naming in both healthy individuals and aphasic patients, or improve grammar learning. In this study, we investigated whether tDCS can be used to increase healthy subjects' performance in phonemic and semantic fluency tasks, that are typically used in clinical assessment of language. Ten healthy individuals performed a semantic and a phonemic fluency task following anodal tDCS applied over Broca's region. Each participant underwent a real and a sham tDCS session. Participants were found to produce more words following real anodal tDCS both in the phonemic and in the semantic fluency. Control experiments ascertained that this finding did not depend upon unspecific effects of tDCS over levels of general arousal or attention or upon participants' expectations. These data confirm the efficacy of tDCS in transiently improving language functions by showing that anodal stimulation of Broca's region can enhance verbal fluency. Implications of these results for the treatment of language functions in aphasia are considered.
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The nature of parietal contributions to working memory (WM) remain poorly understood but of considerable interest. We previously reported that posterior parietal damage selectively impaired WM probed by recognition (Berryhill & Olson, 2008a). Recent studies provided support using a neuromodulatory technique, transcranial direct current stimulation (tDCS) applied to the right parietal cortex (P4). These studies confirmed parietal involvement in WM because parietal tDCS altered WM performance: anodal current tDCS improved performance in a change detection task, and cathodal current) tDCS impaired performance on a sequential presentation task. In Experiment 1, we applied cathodal and anodal tDCS to the right parietal cortex and tested participants on both previously used WM tasks. When the WM task was difficult, parietal stimulation (anodal or cathodal) improved WM performance selectively in participants with high WM capacity. In the low WM capacity group, parietal stimulation (anodal or cathodal) impaired WM performance. These nearly equal and opposite effects were only observed when the WM task was challenging, as in the change detection task. Experiment 2 probed the interplay of WM task difficulty and WM capacity in a parametric manner by varying set size in the WM change detection task. Here, the effect of parietal stimulation (anodal or cathodal) on the high WM capacity group followed a linear function as WM task difficulty increased with set size. These findings provide evidence that parietal involvement in WM performance depends on both WM capacity and WM task demands. We discuss these findings in terms of alternative WM strategies employed by low and high WM capacity individuals. We speculate that low WM capacity individuals do not recruit the posterior parietal lobe for WM tasks as efficiently as high WM capacity individuals. Consequently, tDCS provides