Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

Review of individualized current flow modeling studies for transcranial electrical stimulation.

There is substantial intersubject variability of behavioral and neurophysiological responses to transcranial electrical stimulation (tES), which represents one of the most important limitations of tES. Many tES protocols utilize a fixed experimental parameter set disregarding individual anatomical and physiological properties. This one-size-fits-all approach might be one reason for the observed interindividual response variability. Simulation of current flow applying head models based on available anatomical data can help to individualize stimulation parameters and contribute to the understanding of the causes of this response variability. Current flow modeling can be used to retrospectively investigate the characteristics of tES effectivity. Previous studies examined, for example, the impact of skull defects and lesions on the modulation of current flow and demonstrated effective stimulation intensities in different age groups. Furthermore, uncertainty analysis of electrical conductivities in current flow modeling indicated the most influential tissue compartments. Current flow modeling, when used in prospective study planning, can potentially guide stimulation configurations resulting in individually effective tES. Specifically, current flow modeling using individual or matched head models can be employed by clinicians and scientists to, for example, plan dosage in tES protocols for individuals or groups of participants. We review studies that show a relationship between the presence of behavioral/neurophysiological responses and features derived from individualized current flow models. We highlight the potential benefits of individualized current flow modeling.

Significance of Beta-Band Oscillations in Autism Spectrum Disorders During Motor Response Inhibition Tasks: A MEG Study.

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

The Effects of 1 mA tACS and tRNS on Children/Adolescents and Adults: Investigating Age and Sensitivity to Sham Stimulation.

The aim of this study was to investigate the effect of transcranial random noise (tRNS) and transcranial alternating current (tACS) stimulation on motor cortex excitability in healthy children and adolescents. Additionally, based on our recent results on the individual response to sham in adults, we explored this effect in the pediatric population. We included 15 children and adolescents (10-16 years) and 28 adults (20-30 years). Participants were stimulated four times with 20 Hz and 140 Hz tACS, tRNS, and sham stimulation (1 mA) for 10 minutes over the left M1HAND. Single-pulse MEPs (motor evoked potential), short-interval intracortical inhibition, and facilitation were measured by TMS before and after stimulation (baseline, 0, 30, 60 minutes). We also investigated aspects of tolerability. According to the individual MEPs response immediately after sham stimulation compared to baseline (Wilcoxon signed-rank test), subjects were regarded as responders or nonresponders to sham. We did not find a significant age effect. Regardless of age, 140 Hz tACS led to increased excitability. Incidence and intensity of side effects did not differ between age groups or type of stimulation. Analyses on responders and nonresponders to sham stimulation showed effects of 140 Hz, 20 Hz tACS, and tRNS on single-pulse MEPs only for nonresponders. In this study, children and adolescents responded to 1 mA tRNS and tACS comparably to adults regarding the modulation of motor cortex excitability. This study contributes to the findings that noninvasive brain stimulation is well tolerated in children and adolescents including tACS, which has not been studied before. Finally, our study supports a modulating role of sensitivity to sham stimulation on responsiveness to a broader stimulation and age range.

Efficacy of tRNS and 140 Hz tACS on motor cortex excitability seemingly dependent on sensitivity to sham stimulation.

This study investigates the effect of corticospinal excitability during sham stimulation on the individual response to transcranial non-invasive brain stimulation (tNIBS). Thirty healthy young adults aged 24.2 ± 2.8 S.D. participated in the study. Sham, as well as 1 mA of tRNS and 140 Hz tACS stimulation were applied for 10 min each at different sessions. The effect of each stimulation type was quantified by recording TMS-induced, motor evoked potentials (MEPs) before (baseline) and at fixed time points after stimulation (T0, T30, T60 min.). According to the individual response to sham stimulation at T0 in comparison to baseline MEPs, subjects were regarded as responder or non-responder to sham. Following, MEPs at T0, T30 and T60 after verum or sham stimulation were assessed with a repeated measures ANOVA with the within-subject factor stimulation (sham, tRNS, 140 Hz tACS) and the between-subjects factor group (responder vs non-responder). We found that individuals who did not show immediately changes in excitability in sham stimulation sessions were the ones who responded to active stimulation conditions. On the other hand, individuals who responded to sham condition, by either increases or decreases in MEPS, did not respond to active verum stimulation. This result suggests that the presence or lack of responses to sham stimulation can provide a marker for how individuals will respond to tRNS/tACS and thus provide an explanation for the variability in interindividual response. The results of this study draw attention to the general reactivity of the brain, which can be taken into account when planning future studies using tNIBS.

Predictable information in neural signals during resting state is reduced in autism spectrum disorder.

The neurophysiological underpinnings of the nonsocial symptoms of autism spectrum disorder (ASD) which include sensory and perceptual atypicalities remain poorly understood. Well-known accounts of less dominant top-down influences and more dominant bottom-up processes compete to explain these characteristics. These accounts have been recently embedded in the popular framework of predictive coding theory. To differentiate between competing accounts, we studied altered information dynamics in ASD by quantifying predictable information in neural signals. Predictable information in neural signals measures the amount of stored information that is used for the next time step of a neural process. Thus, predictable information limits the (prior) information which might be available for other brain areas, for example, to build predictions for upcoming sensory information. We studied predictable information in neural signals based on resting-state magnetoencephalography (MEG) recordings of 19 ASD patients and 19 neurotypical controls aged between 14 and 27 years. Using whole-brain beamformer source analysis, we found reduced predictable information in ASD patients across the whole brain, but in particular in posterior regions of the default mode network. In these regions, epoch-by-epoch predictable information was positively correlated with source power in the alpha and beta frequency range as well as autocorrelation decay time. Predictable information in precuneus and cerebellum was negatively associated with nonsocial symptom severity, indicating a relevance of the analysis of predictable information for clinical research in ASD. Our findings are compatible with the assumption that use or precision of prior knowledge is reduced in ASD patients.

No Modulatory Effects when Stimulating the Right Inferior Frontal Gyrus with Continuous 6 Hz tACS and tRNS on Response Inhibition: A Behavioral Study.

Response inhibition is the cognitive process required to cancel an intended action. During that process, a "go" reaction is intercepted particularly by the right inferior frontal gyrus (rIFG) and presupplementary motor area (pre-SMA). After the commission of inhibition errors, theta activity (4-8 Hz) is related to the adaption processes. In this study, we intend to examine whether the boosting of theta activity by electrical stimulation over rIFG reduces the number of errors and the reaction times in a response inhibition task (Go/NoGo paradigm) during and after stimulation. 23 healthy right-handed adults participated in the study. In three separate sessions, theta tACS at 6 Hz, transcranial random noise (tRNS) as a second stimulation condition, and sham stimulation were applied for 20 minutes. Based on behavioral data, this study could not show any effects of 6 Hz tACS as well as full spectrum tRNS on response inhibition in any of the conditions. Since many findings support the relevance of the rIFG for response inhibition, this could mean that 6 Hz activity is not important for response inhibition in that structure. Reasons for our null findings could also lie in the stimulation parameters, such as the electrode montage or the stimulation frequency, which are discussed in this article in more detail. Sharing negative findings will have (1) positive impact on future research questions and study design and will improve (2) knowledge acquisition of noninvasive transcranial brain stimulation techniques.

Comparing the efficacy of excitatory transcranial stimulation methods measuring motor evoked potentials.

The common aim of transcranial stimulation methods is the induction or alterations of cortical excitability in a controlled way. Significant effects of each individual stimulation method have been published; however, conclusive direct comparisons of many of these methods are rare. The aim of the present study was to compare the efficacy of three widely applied stimulation methods inducing excitability enhancement in the motor cortex: 1 mA anodal transcranial direct current stimulation (atDCS), intermittent theta burst stimulation (iTBS), and 1 mA transcranial random noise stimulation (tRNS) within one subject group. The effect of each stimulation condition was quantified by evaluating motor-evoked-potential amplitudes (MEPs) in a fixed time sequence after stimulation. The analyses confirmed a significant enhancement of the M1 excitability caused by all three types of active stimulations compared to sham stimulation. There was no significant difference between the types of active stimulations, although the time course of the excitatory effects slightly differed. Among the stimulation methods, tRNS resulted in the strongest and atDCS significantly longest MEP increase compared to sham. Different time courses of the applied stimulation methods suggest different underlying mechanisms of action. Better understanding may be useful for better targeting of different transcranial stimulation techniques.

Beyond the chronic pain stage: default mode network perturbation depends on years lived with back pain.

ABSTRACT: Research has indicated that the default mode network (DMN) is perturbated in patients with chronic pain when compared with healthy controls, and this perturbation is correlated with the duration of pain during the chronic pain stage. It remains unclear whether DMN adaptations manifest during the subacute pain stage and progress over time because of the duration of pain experience, rather than being a specific correlate of the chronic pain stage. Furthermore, information regarding whether these adaptations are related to cognitive processes of adaptation is lacking. To this end, we examined the DMN in 31 patients with chronic back pain (CBP), 77 patients with subacute back pain (SBP), as well as 39 healthy pain-free controls (HC) applying a graph-theoretic network approach on functional resting-state magnetic resonance imaging. Beyond the comparison between groups, we used a linear analysis considering the years lived with pain (YLP) across all patients with back pain and additionally performed a mediation analysis of the role of cognitive pain coping. In line with previous studies, we found significant DMN perturbation in CBP compared with HC. However, this did not apply to the comparison of CBP with SBP. Instead, we observed a positive correlation between DMN perturbation and YLP. This was significantly mediated by coping attitudes towards pain. Default mode network perturbation may thus reflect neural adaptation processes to pain experience rather than a single correlate of the chronic pain stage and be modulated by cognitive adaption. This points to potentially underinvestigated significant adaptation processes that could enable more fine-grained patient stratification.

Dynamic processes of mindfulness-based alterations in pain perception.

Mindfulness-based processes have been shown to enhance attention and related behavioral responses, including analgesia, which is discussed as an effective method in the context of pain interventions. In the present review, we introduce the construct of mindfulness, delineating the concepts, factors, and processes that are summarized under this term and might serve as relevant components of the underlying mechanistic pathways in the field of pain. We also discuss how differences in factors such as definitions of mindfulness, study design, and strategies in mindfulness-based attention direction may need to be considered when putting the findings from previous studies into a whole framework. In doing so, we capitalize on a potential dynamic process model of mindfulness-based analgesia. In this respect, the so-called mindfulness-based analgesia may initially result from improved cognitive regulation strategies, while at later stages of effects may be driven by a reduction of interference between both cognitive and affective factors. With increasing mindfulness practice, pathways and mechanisms of mindfulness analgesia may change dynamically, which could result from adaptive coping. This is underlined by the fact that the neural mechanism of mindfulness analgesia is manifested as increased activation in the ACC and aINS at the beginner level while increased activation in the pINS and reduced activation in the lPFC at the expert level.

Offline 20 Hz transcranial alternating current stimulation over the right inferior frontal gyrus increases theta activity during a motor response inhibition task.

OBJECTIVES: Previous studies have shown that the right inferior frontal gyrus (rIFG) and the pre-supplementary motor area (preSMA) play an important role in motor inhibitory control. The aim of the study was to use theta frequency transcranial alternating current stimulation (tACS) to modulate brain activity in the rIFG and preSMA and to test the effects of stimulation using a motor response inhibition task. METHODS: In four sessions, 20 healthy participants received tACS at 6 Hz over preSMA or rIFG, or 20 Hz over rIFG (to test frequency specificity), or sham stimulation before task processing. After each type of stimulation, the participants performed the Go/NoGo task with simultaneous electroencephalogram (EEG) recording. RESULTS: By stimulating rIFG and preSMA with 6 Hz tACS, we were not able to modulate either behavioral performance nor the EEG correlate. Interestingly, 20 Hz tACS over the rIFG significantly increased theta activity, however without behavioral effects. This increased theta activity did not coincide with the stimulation area and was localized in the fronto-central and centro-parietal areas. CONCLUSIONS: The inclusion of a control frequency is crucial to test for frequency specificity. Our findings are in accordance with previous studies showing that after effects of tACS are not restricted to the stimulation frequency but can also occur in other frequency bands.

The association of spouse interactions and emotional learning in interference related to chronic back pain.

Social interactions affect individual behaviours, preferences, and attitudes. This is also critical in the context of experiencing pain and expressing pain behaviours, and may relate to learned emotional responses. In this respect, individual variability in the medial prefrontal cortex (mPFC), which is involved in adjusting an organism's behaviour to its environment by evaluating and interpreting information within the context of past experiences, is important. It is critical for selecting suitable behavioural responses within a social environment and may reinforce maladaptation in chronic pain. In our study, we used brain imaging during appetitive and aversive pavlovian conditioning in persons with chronic back pain (CBP), subacute back pain (SABP), and healthy controls (HC), together with information on spouse responses to pain behaviours. We also examined the relationship of these responses with pain-related interference in the patients. Our findings yielded a significant negative association between mPFC responses to appetitive and aversive learning in CBP. We also observed a significant negative association for mPFC responses during aversive learning and distracting spouse responses, and a significant positive association between mPFC responses during appetitive learning and solicitous spouse responses in CBP. Both significantly predicted pain-related interference in the CBP group (explained variance up to 53%). Significant associations were not found for SABP or HC. Our findings support an association between appetitive and aversive pavlovian learning, related brain circuits and spouse responses to pain in CBP, where appetitive and aversive learning processes seem to be differentially involved. This can inform prevention and early intervention in a mechanistic approach.

Stratification of responses to tDCS intervention in a healthy pediatric population based on resting-state EEG profiles.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique with a wide variety of clinical and research applications. As increasingly acknowledged, its effectiveness is subject dependent, which may lead to time consuming and cost ineffective treatment development phases. We propose the combination of electroencephalography (EEG) and unsupervised learning for the stratification and prediction of individual responses to tDCS. A randomized, sham-controlled, double-blind crossover study design was conducted within a clinical trial for the development of pediatric treatments based on tDCS. The tDCS stimulation (sham and active) was applied either in the left dorsolateral prefrontal cortex or in the right inferior frontal gyrus. Following the stimulation session, participants performed 3 cognitive tasks to assess the response to the intervention: the Flanker Task, N-Back Task and Continuous Performance Test (CPT). We used data from 56 healthy children and adolescents to implement an unsupervised clustering approach that stratify participants based on their resting-state EEG spectral features before the tDCS intervention. We then applied a correlational analysis to characterize the clusters of EEG profiles in terms of participant's difference in the behavioral outcome (accuracy and response time) of the cognitive tasks when performed after a tDCS-sham or a tDCS-active session. Better behavioral performance following the active tDCS session compared to the sham tDCS session is considered a positive intervention response, whilst the reverse is considered a negative one. Optimal results in terms of validity measures was obtained for 4 clusters. These results show that specific EEG-based digital phenotypes can be associated to particular responses. While one cluster presents neurotypical EEG activity, the remaining clusters present non-typical EEG characteristics, which seem to be associated with a positive response. Findings suggest that unsupervised machine learning can be successfully used to stratify and eventually predict responses of individuals to a tDCS treatment.

No effects of prefrontal multichannel tACS at individual alpha frequency on phonological decisions.

OBJECTIVE: Alpha oscillations are linked to inhibitory capabilities in higher cognitive processing. Transcranial alternating current stimulation (tACS) at 10 Hz can enhance alpha oscillations and modulate behaviour. One possibility to increase the efficacy of tACS may be stimulating at the individual alpha frequency (IAF). The present work addresses this issue (among others) to increase the current understanding of the functional role of alpha oscillations in higher cognitive tasks. METHODS: Twenty-two healthy and 13 dyslexic participants performed two word decision tasks while receiving IAF-tACS over the left prefrontal cortex. Resting EEG was recorded to detect electrophysiological changes. Cortical excitability was assessed with TMS. RESULTS: Dyslexic participants performed worse in the phonological task. However, no significant tACS effects were found. Interestingly, higher cortical excitability was correlated with faster responses in healthy controls. In dyslexics this association significantly differed in the phonological task. CONCLUSION: The non-significant modulation by tACS might be explained by methodological limitations. Alternatively, it may indicate that alpha oscillations do not play a functional role in phonological decisions. The findings on cortical excitability expands the existing literature and may reflect the specific phonological deficit in dyslexics. SIGNIFICANCE: Our critical discussion of these null findings expands the systematic knowledge on alpha-tACS for future studies.

Non-invasive brain stimulation and neuroenhancement.

Attempts to enhance human memory and learning ability have a long tradition in science. This topic has recently gained substantial attention because of the increasing percentage of older individuals worldwide and the predicted rise of age-associated cognitive decline in brain functions. Transcranial brain stimulation methods, such as transcranial magnetic (TMS) and transcranial electric (tES) stimulation, have been extensively used in an effort to improve cognitive functions in humans. Here we summarize the available data on low-intensity tES for this purpose, in comparison to repetitive TMS and some pharmacological agents, such as caffeine and nicotine. There is no single area in the brain stimulation field in which only positive outcomes have been reported. For self-directed tES devices, how to restrict variability with regard to efficacy is an essential aspect of device design and function. As with any technique, reproducible outcomes depend on the equipment and how well this is matched to the experience and skill of the operator. For self-administered non-invasive brain stimulation, this requires device designs that rigorously incorporate human operator factors. The wide parameter space of non-invasive brain stimulation, including dose (e.g., duration, intensity (current density), number of repetitions), inclusion/exclusion (e.g., subject's age), and homeostatic effects, administration of tasks before and during stimulation, and, most importantly, placebo or nocebo effects, have to be taken into account. The outcomes of stimulation are expected to depend on these parameters and should be strictly controlled. The consensus among experts is that low-intensity tES is safe as long as tested and accepted protocols (including, for example, dose, inclusion/exclusion) are followed and devices are used which follow established engineering risk-management procedures. Devices and protocols that allow stimulation outside these parameters cannot claim to be "safe" where they are applying stimulation beyond that examined in published studies that also investigated potential side effects. Brain stimulation devices marketed for consumer use are distinct from medical devices because they do not make medical claims and are therefore not necessarily subject to the same level of regulation as medical devices (i.e., by government agencies tasked with regulating medical devices). Manufacturers must follow ethical and best practices in marketing tES stimulators, including not misleading users by referencing effects from human trials using devices and protocols not similar to theirs.

Cortical current density magnitudes during transcranial direct current stimulation correlate with skull thickness in children, adolescent and young adults.

Transcranial direct current stimulation protocols are often applied with a fixed parameter set to all subjects participating in an interventional study. This might lead to considerable effect variation in inhomogeneous subject groups or when transferring stimulation protocols to different age groups. The aim of this study was to evaluate magnitude differences of the electric current density distribution on the gray matter surface in children, adolescent and adults in correlation with the individual volume conductor geometry. We generated individual six compartment finite element models from structural magnetic resonance images of four children (age: 10.95 a±1.32 a), eight adolescents (age: 15.10 a±1.16 a) and eight young adults (age: 21.62 a±2.45 a). We determined the skull thickness in the models as Euclidean distance between the surface of the cerebrospinal fluid compartment and outer skull boundary. For tDCS simulations, we modeled 5×7cm patch electrodes impressing 1mA current intensity as anode and cathode over the left M1 and the right fronto-polar orbit, respectively. The resulting current density was analyzed on the gray matter surface. Our results demonstrate higher cortical current density magnitudes in children compared to adults for a given tDCS current strength. Above the evaluated cortex, the skull thickness increased with age. In conclusion, we underline the importance of age-dependent and individual models in tDCS simulations.

Brain Circuits Involved in the Development of Chronic Musculoskeletal Pain: Evidence From Non-invasive Brain Stimulation.

It has been well-documented that the brain changes in states of chronic pain. Less is known about changes in the brain that predict the transition from acute to chronic pain. Evidence from neuroimaging studies suggests a shift from brain regions involved in nociceptive processing to corticostriatal brain regions that are instrumental in the processing of reward and emotional learning in the transition to the chronic state. In addition, dysfunction in descending pain modulatory circuits encompassing the periaqueductal gray and the rostral anterior cingulate cortex may also be a key risk factor for pain chronicity. Although longitudinal imaging studies have revealed potential predictors of pain chronicity, their causal role has not yet been determined. Here we review evidence from studies that involve non-invasive brain stimulation to elucidate to what extent they may help to elucidate the brain circuits involved in pain chronicity. Especially, we focus on studies using non-invasive brain stimulation techniques [e.g., transcranial magnetic stimulation (TMS), particularly its repetitive form (rTMS), transcranial alternating current stimulation (tACS), and transcranial direct current stimulation (tDCS)] in the context of musculoskeletal pain chronicity. We focus on the role of the motor cortex because of its known contribution to sensory components of pain via thalamic inhibition, and the role of the dorsolateral prefrontal cortex because of its role on cognitive and affective processing of pain. We will also discuss findings from studies using experimentally induced prolonged pain and studies implicating the DLPFC, which may shed light on the earliest transition phase to chronicity. We propose that combined brain stimulation and imaging studies might further advance mechanistic models of the chronicity process and involved brain circuits. Implications and challenges for translating the research on mechanistic models of the development of chronic pain to clinical practice will also be addressed.

Transcranial direct current stimulation in attention-deficit/hyperactivity disorder: A meta-analysis of clinical efficacy outcomes.

BACKGROUND: Evidence for the application of transcranial direct current stimulation (tDCS) in the clinical care of attention-deficit/hyperactivity disorder (ADHD) is limited. Therefore, we aimed to summarize study results using meta-analyses of measures of the cardinal symptoms of ADHD. METHODS: We conducted a systematic literature search (PubMed/pubpsych/PsychInfo/WOS) until 01/05/2020 for randomized controlled trials (RCTs) evaluating tDCS vs. control condition in patients with ADHD. A random effects meta-analysis of symptom-related outcomes was performed separately for data on the immediate effect and follow-up. Subgroup- and metaregression analyses for patient characteristics and tDCS parameters were included. RESULTS: Meta-analyzing 13 studies (n=308, age=23.7±13.3), including 20 study arms, tDCS had an immediate effect on overall symptom severity, inattention, and impulsivity, but not on hyperactivity. Results were significant in children and adolescents (8 studies, n=133, age=12.4±3.0). Follow-up data (3 days-4 weeks after stimulation) suggested an ongoing beneficial effect regarding overall symptom severity and a delayed effect on hyperactivity. DISCUSSION: TDCS seems to be a promising method to treat clinical symptoms in ADHD with long-lasting effects. Still, more research considering the individual neuropsychological and anatomical dispositions of the subjects is needed to optimize tDCS protocols and efficacy. Safety issues of tDCS treatment in children and adolescents are addressed.

Online Effects of Beta-tACS Over the Left Prefrontal Cortex on Phonological Decisions.

The left posterior inferior frontal gyrus in the prefrontal cortex is a key region for phonological aspects of language processing. A previous study has shown that alpha-tACS over the prefrontal cortex applied before task processing facilitated phonological decision-making and increased task-related theta power. However, it is unclear how alpha-tACS affects phonological processing when applied directly during the task. Moreover, the frequency specificity of this effect is also unclear since the majority of neurostimulation studies tested a single frequency only. The present study addressed the question whether and how 10 Hz online tACS affects phonological decisions. To this end, 24 healthy participants received tACS at 10 Hz or 16.18 Hz (control frequency) or sham stimulation over the left prefrontal cortex during task processing in three sessions. As an unexpected finding, 16.18 Hz significantly impaired task accuracy relative to sham stimulation, without affecting response speed. There was no significant difference in phonological task performance between 10 Hz and 16.18 Hz tACS or between 10 Hz and sham stimulation. Our results support the functional relevance of the left prefrontal cortex for phonological decisions and suggest that online beta-tACS may modulate language comprehension.

Multichannel anodal tDCS over the left dorsolateral prefrontal cortex in a paediatric population.

Methodological studies investigating transcranial direct current stimulation (tDCS) over the left dorsolateral prefrontal cortex (lDLPFC) in paediatric populations are limited. Therefore, we investigated in a paediatric population whether stimulation success of multichannel tDCS over the lDLPFC depends on concurrent task performance and individual head anatomy. In a randomised, sham-controlled, double-blind crossover study 22 healthy participants (10-17 years) received 2 mA multichannel anodal tDCS (atDCS) over the lDLPFC with and without a 2-back working memory (WM) task. After stimulation, the 2-back task and a Flanker task were performed. Resting state and task-related EEG were recorded. In 16 participants we calculated the individual electric field (E-field) distribution. Performance and neurophysiological activity in the 2-back task were not affected by atDCS. atDCS reduced reaction times in the Flanker task, independent of whether atDCS had been combined with the 2-back task. Flanker task related beta oscillation increased following stimulation without 2-back task performance. atDCS effects were not correlated with the E-field. We found no effect of multichannel atDCS over the lDLPFC on WM in children/adolescents but a transfer effect on interference control. While this effect on behaviour was independent of concurrent task performance, neurophysiological activity might be more sensitive to cognitive activation during stimulation. However, our results are limited by the small sample size, the lack of an active control group and variations in WM performance.