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Neurobehavioral studies have provided evidence for the effectiveness of anodal tDCS on language production, by stimulation of the left Inferior Frontal Gyrus (IFG) or of left Temporo-Parietal Junction (TPJ). However, tDCS is currently not used in clinical practice outside of trials, because behavioral effects have been inconsistent and underlying neural effects unclear. Here, we propose to elucidate the neural correlates of verb and noun learning and to determine if they can be modulated with anodal high-definition (HD) tDCS stimulation. Thirty-six neurotypical participants were randomly allocated to anodal HD-tDCS over either the left IFG, the left TPJ, or sham stimulation. On day one, participants performed a naming task (pre-test). On day two, participants underwent a new-word learning task with rare nouns and verbs concurrently to HD-tDCS for 20 min. The third day consisted of a post-test of naming performance. EEG was recorded at rest and during naming on each day. Verb learning was significantly facilitated by left IFG stimulation. HD-tDCS over the left IFG enhanced functional connectivity between the left IFG and TPJ and this correlated with improved learning. HD-tDCS over the left TPJ enabled stronger local activation of the stimulated area (as indexed by greater alpha and beta-band power decrease) during naming, but this did not translate into better learning. Thus, tDCS can induce local activation or modulation of network interactions. Only the enhancement of network interactions, but not the increase in local activation, leads to robust improvement of word learning. This emphasizes the need to develop new neuromodulation methods influencing network interactions. Our study suggests that this may be achieved through behavioral activation of one area and concomitant activation of another area with HD-tDCS.

Background: Bipolar disorder is classified as one of the most debilitating mental diseases. Although patients receive medical treatment, cognitive deficits remain in the euthymic phase in many patients. It is hypothesized that brain electrical stimulation protocols that increase cognitive function may increase the quality of life. Therefore, this study aimed to evaluate the effectiveness of transcranial direct current stimulation in improving cognitive function in bipolar patients in the euthymic phase. Methods & Materials: In a double-blind, sham-controlled- clinical trial, 46 euthymic bipolar patients diagnosed based on DSM-V were randomly divided into the two intervention and control groups. tDCS was applied for the intervention group using an anode electrode at the left dorsolateral-peripheral cortex (F3) and the cathode at the right dorsolateral-frontal (F4) (based on the 10/20 system) at 2 mA for 20 min. The Strop Color and Word Test, The Rey Auditory Verbal Learning Test (RAVLT), and The Wechsler Adult Intelligence Scale (WAISR) were evaluated before, at the end of the third and the seventh weeks of the intervention. Statistical analysis was performed using SPSS v 16. Results: The scores of immediate and delayed auditory memory and visual memory in the intervention group, unlike the control group, improved significantly after treatment. Moreover, Wechsler's working memory score in the intervention group improved significantly after treatment. Consistent and inconsistent answers scores were also significantly improved in the intervention group compared with the controls. Conclusion: The present study indicated that tDCS might be an efficient and safe method for improving cognitive function in euthymic bipolar patients.

Transcranial direct current stimulation (tDCS) targeting the prefrontal cortex has emerged as a valuable tool in psychiatric research. Understanding the impact of affective states, such as stress at the time of stimulation, on the efficacy of prefrontal tDCS is crucial for advancing tDCS interventions. Stress-primed tDCS, wherein stress is used as a priming agent, has the potential to modulate neural plasticity and enhance cognitive functions, particularly in emotional working memory. However, prior research using stress-primed tDCS focused solely on non-emotional working memory performance, yielding mixed results. In this sham-controlled study, we addressed this gap by investigating the effects of stress-primed bifrontal tDCS (active versus sham) on both non-emotional and emotional working memory performance. The study was conducted in 146 healthy individuals who were randomly assigned to four experimental groups. The Trier Social Stress Test (TSST) or a control variant of the test was used to induce a stress versus control state. The results showed that stress priming significantly enhanced the effects of tDCS on the updating of emotional content in working memory, as evidenced by improved accuracy. Notably, no significant effects of stress priming were found for non-emotional working memory performance. These findings highlight the importance of an individual's prior affective state in shaping their response to tDCS, especially in the context of emotional working memory.

Background: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing. Objectives: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures. Methods: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals. Results: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model. Conclusions: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.

Background: Post-stroke fatigue (PSF) is one of the most prevalent symptoms that affects quality of life and daily function after stroke. Despite a growing body of research, its pathophysiology is poorly understood. Non-invasive brain stimulation (NIBS), such as the transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), can serve as a non-pharmacological intervention for PSF. In this review, we aim to (1) evaluate PSF neuroimaging studies to deduce potential neural mechanisms, (2) describe NIBS as a tool to probe brain structures to further understand pathophysiology of fatigue, and (3) assess NIBS as a treatment intervention for PSF., Methods: A systematic search was conducted for the databases PubMed, Embase, Scopus, CINAHL and Cochrane. Studies were included based on the following inclusion and exclusion criteria: >18 years with PSF, use of neuroimaging and/or NIBS for investigation or as an intervention for PSF, English language, study types including cohort, case control, or randomized controlled trials. Data extracted included participant characteristics, concept, context, study methods, and key findings relevant to the review questions., Results: A total of 30 studies met criteria. Neuroimaging papers that investigated brain structure (MRI) found conflicting associations between lesion location and PSF. Functional methods (fMRI, TMS) revealed altered resting state functional connectivity (rsFC), cortical excitability, and a disruption in interhemispheric inhibitory balance as potential mechanisms of PSF. There were no studies using TMS as an intervention for PSF. Of the six articles that used tDCS, only two reported statistically significant reductions in the severity of PSF., Conclusion: Structural characteristics of stroke lesions had conflicting findings, while functional neuroimaging studies suggested that altered rsFC, cortical excitability and interhemispheric inhibitory balance contribute to the development of PSF. There were inconsistent results on the effectiveness of tDCS as an intervention for PSF, due to varying methodologies and lack of precise targeting of underlying neural mechanisms. Further investigations are needed to determine if NIBS could be a potential treatment to alleviate the effects of PSF., Competing Interests: Declaration of competing interest Michele Soltsov – none Doo Hee Jang – none Ji Hyun Kim – none. Alexandra Keenan – none. Kevin Pain – none. Abhishek Jaywant – full time salaried faculty member, Weill Cornell Medicine. Receives salary support from the National Institutes of Health (grant K23MH129849). Has received fees for consulting with Axem Neurotechnology Inc. Receives royalties from Oxford University Press for a published psychotherapy manual for individuals with long COVID. Joan Stilling – full time salaried faculty member, Weill Cornell Medicine. Site PI for industry sponsored clinical trials: 1) Merz Pharmaceuticals. Prospective, randomized, double-blind, placebo-controlled, multicenter study to investigate the efficacy and safety of NT 201 in the treatment of lower limb spasticity caused by stroke or traumatic brain injury in adult subjects, followed by an open label extension with or without combined upper limb treatment. 2) Ipsen Pharmaceuticals. A Multicentre, Interventional, Post-marketing, Randomized, Double-blind, Crossover Study to Evaluate the Clinical Safety and Efficacy of AbobotulinumtoxinA (Dysport®) in Comparison with OnabotulinumtoxinA (Botox®) when Treating Adults with Upper Limb Spasticity., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Innovative treatments for paranoia, which significantly impairs social functioning in schizophrenia (SCZ), are urgently needed. The pathophysiology of paranoia implicates the amygdala-prefrontal (PFC) circuits; thus, this study systematically investigated whether transcranial direct current stimulation (tDCS) to the ventrolateral PFC can attenuate paranoia and improve social functioning in SCZ., Methods: A double-blind, within-subjects, crossover design was used to compare active vs. sham tDCS effects in 50 participants with SCZ (ClinicalTrials.gov Identifier: NCT05746494). Participants completed two stimulation visits, each including two tDCS sessions about a week apart, with active (2mA for 20mins) and sham conditions counterbalanced across the two visits. Alongside lab-based measurements of state paranoia and its associated social cognitive biases, Ecological Momentary Assessment (EMA) was used. This involved daily evaluations of paranoia and social functioning, administered three times per day for seven days in each EMA period (EMA-baseline, EMA-active, EMA-sham)., Results: For lab-based assessments, participants showed greater reductions in state paranoia and improvements in paranoia-related social cognitive biases after active stimulation compared to sham, including lower self-reported hostility and hostile attributions in ambiguous situations post-active versus post-sham. Similarly, in the EMA-active period, participants had lower daily paranoia compared to the EMA-sham period and higher social interaction motivation with better attitudes compared to baseline and the EMA-sham period., Conclusions: Extending our pilot study, the current findings further supported the efficacy of tDCS in SCZ patients in mitigating paranoia and enhancing social functioning. This work sheds light on the neuropathology of paranoia and identifies a promising avenue for future large-scale interventions., (Copyright © 2025. Published by Elsevier Inc.)

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner.

Background: Many studies have shown effects of anodal transcranial direct current stimulation (a-tDCS) and high-frequency transcranial random noise stimulation (tRNS) on elevating cortical excitability. Moreover, tRNS with a direct current (DC)-offset is more likely to lead to increases in cortical excitability than solely tRNS. While a-tDCS over primary motor cortex (M1) has been shown to attenuate pain perception, tRNS + DC-offset may prove as an effective means for pain relief. Objective: This study aimed to examine effects of a-tDCS and high-frequency tRNS + DC-offset over M1 on pain expectation and perception, and assess whether these effects could be influenced by the certainty of pain expectation. Methods: Using a double-blinded and sham-controlled design, 150 healthy participants were recruited to receive a single-session a-tDCS, high-frequency tRNS + DC-offset, or sham stimulation over M1. The expectation and perception of electrical stimulation in certain and uncertain contexts were assessed at baseline, immediately after, and 30 min after stimulation. Results: Compared with sham stimulation, a-tDCS induced immediate analgesic effects that were greater when the stimulation outcome was expected with uncertainty; tRNS induced immediate and sustained analgesic effects that were mediated by decreasing pain expectation. Nevertheless, we found no strong evidence for tRNS being more effective for attenuating pain than a-tDCS. Conclusions: The analgesic effects of a-tDCS and tRNS showed different temporal courses, which could be related to the more sustained effectiveness of high-frequency tRNS + DC-offset in elevating cortical excitability. Moreover, expectations of pain intensity should be taken into consideration to maximize the benefits of neuromodulation.

Background: Transcranial direct current stimulation (tDCS) provides a noninvasive polarity-specific constant current to treat epilepsy, through a mechanism possibly involving excitability modulation and neural oscillation. Objective: To determine whether EEG oscillations underlie the interictal spike changes after tDCS in rats with chronic spontaneous seizures. Methods: Rats with kainic acid-induced spontaneous seizures were subjected to cathodal tDCS or sham stimulation for 5 consecutive days. Video-EEG recordings were collected immediately pre- and post-stimulation and for the subsequent 2 weeks following stimulation. The acute pre-post stimulation and subacute follow-up changes of interictal spikes and EEG oscillations in tDCS-treated rats were compared with sham. Ictal EEG with seizure behaviors, hippocampal brain-derived neurotrophic factor (BDNF) protein expression, and mossy fiber sprouting were compared between tDCS and sham rats. Results: Interictal spike counts were reduced immediately following tDCS with augmented delta and diminished beta and gamma oscillations compared with sham. Cathodal tDCS also enhanced delta oscillations in normal rats. However, increased numbers of interictal spikes with a decrease of delta and theta oscillations were observed in tDCS-treated rats compared with sham during the following 2 weeks after stimulation. Resuming tDCS suppressed the increase of interictal spike activity. In tDCS rats, hippocampal BDNF protein expression was decreased while mossy fiber sprouting did not change compared with sham. Conclusions: The inverse relationship between the changes of delta oscillation and interictal spikes during tDCS on and off stimulation periods indicates that an enhanced endogenous delta oscillation underlies the tDCS inhibitory effect on epileptic excitability.

Background: Social Anxiety Disorder (SAD) is the most common anxiety disorder while remains largely untreated. Disturbed amygdala-frontal network functions are central to the pathophysiology of SAD, marked by hypoactivity of the lateral prefrontal cortex (PFC), and hypersensitivity of the medial PFC and the amygdala. The objective of this study was to determine whether modulation of the dorsolateral and medial PFC activity with a novel intensified stimulation protocol reduces SAD core symptoms, improves treatment-related variables, and reduces attention bias to threatening stimuli. Methods: In this randomized, sham-controlled, double-blind trial, we assessed the efficacy of an intensified stimulation protocol (20 min, twice-daily sessions with 20 min intervals, 5 consecutive days) in two intensities (1 vs 2 mA) compared to sham stimulations. 45 patients with SAD were randomized in three tDCS arms (1-mA, 2-mA, sham). SAD symptoms, treatment-related variables (worries, depressive state, emotion regulation, quality of life), and attention bias to threatening stimuli (dot-probe paradigm) were assessed before and right after the intervention. SAD symptoms were also assessed at 2-month follow-up. Results: Both 1-mA and 2-mA protocols significantly reduced fear/avoidance symptoms, worries and improved, emotion regulation and quality of life after the intervention compared to the sham group. Improving effect of the 2-mA protocol on avoidance symptoms, worries and depressive state was significantly larger than the 1-mA group. Only the 2-mA protocol reduced attention bias to threat-related stimuli, the avoidance symptom at follow-up, and depressive states, as compared to the sham group. Conclusions: Modulation of lateral-medial PFC activity with intensified stimulation can improve cognitive control, motivation and emotion networks in SAD and might thereby result in therapeutic effects. These effects can be larger with 2-mA vs 1-mA intensities, though a linear relationship between intensity and efficacy should not be concluded. Our results need replication in larger trials.

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.

Background: Transcranial electrical stimulation (tES) shows promise to treat neurological disorders. Knowledge of how the orthogonal components of the electric field (E-field) alter neuronal activity is required for strategic placement of transcranial electrodes. Yet, essentially no information exists on this relationship for mammalian cerebellum in vivo, despite the cerebellum being a target for clinical tES studies. Objective: To characterize how cerebellar Purkinje cell (PC) activity varies with the intensity, frequency, and direction of applied AC and DC E-fields. Methods: Extracellular recordings were obtained from vermis lobule 7 PCs in anesthetized rats. AC (2–100 Hz) or DC E-fields were generated in a range of intensities (0.75–30 mV/mm) in three orthogonal directions. Field-evoked PC simple spike activity was characterized in terms of firing rate modulation and phase-locking as a function of these parameters. t-tests were used for statistical comparisons. Results: The effect of applied E-fields was direction and intensity dependent, with rostrocaudally directed fields causing stronger modulations than dorsoventral fields and mediolaterally directed ones causing little to no effect, on average. The directionality dependent modulation suggests that PC is the primary cell type affected the most by electric stimulation, and this effect was probably given rise by a large dendritic tree and a soma. AC stimulation entrained activity in a frequency dependent manner, with stronger phase-locking to the stimulus cycle at higher frequencies. DC fields produced a modulation consisting of strong transients at current onset and offset with an intervening plateau. Conclusion: Orientation of the exogenous E-field critically determines the modulation depth of cerebellar cortical output. With properly oriented fields, PC simple spike activity can strongly be entrained by AC fields, overriding the spontaneous firing pattern.

Background: According to the neurocognitive model of addiction, the development and maintenance of drug addiction is associated with cognitive control deficits, as well as decreased activity of prefrontal regions, especially the dorsolateral prefrontal cortex (DLPFC). This study investigated how improving executive functions (EFs) impacts methamphetamine-use disorder, which has been less explored compared to craving, but might be a central aspect for the therapeutic efficacy of DLPFC stimulation in drug addiction. Methods: We assessed the efficacy of 10 repeated sessions of transcranial direct current stimulation (tDCS) over the DLPFC on executive dysfunctions in methamphetamine-use disorder, and its association with craving alterations. 39 of 50 initially recruited individuals with methamphetamine-use disorder who were in the abstinent-course treatment were randomly assigned to “active” and “sham” stimulation groups in a randomized, double-blind parallel-group study. They received active (2 mA, 20 min) or sham tDCS for 10 sessions over 5 weeks. Performance on major EF tasks (e.g., working memory, inhibitory control, cognitive flexibility, and risk-taking behaviour) and craving were measured before, immediately after, and 1 month following the intervention. Participants reported abstinence from drug consumption throughout the experiment, verified by regular urine tests during the course of the study up to the follow-up measurement. Results: The group which received active DLPFC tDCS showed significantly improved task performance across all EFs immediately after and 1 month following the intervention, when compared to both pre-stimulation baseline and individuals who received sham tDCS. Similarly, a significant reduction in craving was observed immediately after and 1 month following the intervention in the active, but not sham stimulation group. A significant correlation between cognitive control improvement and craving reduction was found as well. Conclusions: Improvement of cognitive control functions is closely associated with reduced craving. Repeated DLPFC stimulation in order to improve executive control could be a promising approach for therapeutic interventions in drug addiction. However, the observed findings require further confirmation by studies that measure relapse/consumption of the respective substances over longer follow-up measurements.

Background: Transcranial direct current stimulation (tDCS) is a method of noninvasive neuromodulation and potential therapeutic tool to improve functioning and relieve symptoms across a range of central and peripheral nervous system conditions. Evidence suggests that the effects of tDCS are cumulative with consecutive daily applications needed to achieve clinically meaningful effects. Therefore, there is growing interest in delivering tDCS away from the clinic or research facility, usually at home. Objective: To provide a comprehensive guide to operationalize safe and responsible use of tDCS in home settings for both investigative and clinical use. Methods: Providing treatment at home can improve access and compliance by decreasing the burden of time and travel for patients and their caregivers, as well as to reach those in remote locations and/or living with more advanced disabilities. Results: To date, methodological approaches for at-home tDCS delivery have varied. After implementing the first basic guidelines for at-home tDCS in clinical trials, this work describes a comprehensive guide for facilitating safe and responsible use of tDCS in home settings enabling access for repeated administration over time. Conclusion: These guidelines provide a reference and standard for practice when employing the use of tDCS outside of the clinic setting.

Transcranial direct current stimulation (tDCS) targeting Broca's area has shown promise for augmenting language production in post-stroke aphasia (PSA). However, previous research has been limited by small sample sizes and inconsistent outcomes. This study employed a double-blind, parallel, randomized, controlled design to evaluate the efficacy of anodal Broca's tDCS, paired with 20-minute speech and language therapy (SLT) focused primarily on expressive language, across 5 daily sessions in 45 chronic PSA patients. Utilizing the Western Aphasia Battery-Revised, which assesses a spectrum of linguistic abilities, we measured changes in both expressive and receptive language skills before and after intervention. The tDCS group demonstrated significant improvements over sham in aphasia quotient, auditory verbal comprehension, and spontaneous speech. Notably, tDCS improved both expressive and receptive domains, whereas sham only benefited expression. These results underscore the broader linguistic benefits of Broca's area stimulation and support the integration of tDCS with SLT to advance aphasia rehabilitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Transcranial direct current stimulation (tDCS) is a type of non-invasive brain stimulation technique that is explored as an add-on treatment for the alleviation of symptoms across the diverse symptom domains in neuropsychiatric disorders. In psychiatry, data is emerging on the effects of tDCS as an add-on treatment in schizophrenia as well as obsessive-compulsive disorder (OCD). But despite high prevalence, the effectiveness of tDCS in co-morbid schizophrenia and OCD is lacking. This case report for the first time examines the clinical utility with target-specific effects of the add-on tDCS in a patient diagnosed with schizo-obsessive disorder.

Background: The prefrontal cortex is crucial for top-down regulation of aggression, but the neural underpinnings of aggression are still poorly understood. Past research showed the transcranial direct current stimulation (tDCS) over the ventrolateral prefrontal cortex (VLPFC) modulates aggression following exposure to risk factors for aggression (e.g., social exclusion, violent media). Although frustration is a key risk factor for aggression, no study to date has examined the modulatory role of tDCS on frustration-induced aggression. Objectives: By exploring the VLPFC involvement in frustration-aggression link, we tested the hypothesis that the anodal tDCS over right and left VLPFC modulates frustration-induced aggression. We also explored whether tDCS interacts with gender to influence frustration-induced aggression. Methods: 90 healthy participants (45 men) were randomly assigned to receive anodal or sham tDCS over the right or left VLPFC before being frustrated by an accomplice. To increase reliability, several tasks were used to measure aggression. Results: We found that anodal tDCS over the left VLPFC, compared to sham stimulation, increased aggression. Unexpectedly, no main effect was found following tDCS of right VLPFC. However, we also found a significant interaction between gender and tDCS, showing that males were more aggressive than females following sham stimulation, but females became as aggressive as males following active tDCS. Conclusion: Overall, these results shed light on the neural basis of frustration-induced aggression, providing further evidence for the involvement of VLPFC in modulating aggressive responses, and on gender differences in aggression. Future research should further investigate the role of stimulating the VLPFC on frustration-induced aggression.

Background: Transcranial direct current stimulation (tDCS) has been explored in epilepsy with limited samples, varied parameters, and inconclusive results. We aimed to study the efficacy of tDCS for patients with refractory focal epilepsy. Method: We conducted a randomized, double-blind, sham-controlled, and three-arm (Group 1 (sham), Group 2 (20-min), and Group 3 (2 × 20-min)) tDCS parallel multicenter study. The primary outcome measurement was seizure frequencies (SFs). The study consisted of 28-days baseline, 14-days treatment, and 56-days follow-up. The cathode was placed over the epileptogenic focus, and the current intensity was 2 mA. The generalized estimating equations model, one-way analysis of variance, chi-square and Kruskal-Wallis test were used for analysis. Results: Of the 82 enrolled patients, 70 patients were included for final analysis (Group 1, n = 21; Group 2, n = 24; and Group 3, n = 25). There was a significant reduction in SFs for both active tDCS groups compared with the sham group. Patients in Group 2 showed a significantly 50.73–21.91% greater reduction in SFs that lasted for 4 weeks (p = 0.008–0.060). Patients in Group 3 showed a significantly 63.19–49.79% greater reduction in SFs compared with the sham group that lasted for 5 weeks (p = 0.011–0.045). Patients in Group 3 had a 64.98–66.32% greater reduction in SFs at W9–W10, when compared with Group 2 (p = 0.021–0.022). Conclusion: Fourteen consecutive days tDCS significantly decreased SFs in patients with refractory focal epilepsy, with 2 × 20-min daily stimulation protocol being superior to 20-min daily stimulation protocol.

Transcranial Direct Current Stimulation (tDCS), a safe and easy-to-administer noninvasive brain stimulation technique, holds promise in managing auditory verbal hallucinations (AVH) in schizophrenia. However, its short-lasting effect often leads to frequent hospital visits for booster/maintenance sessions, posing logistical challenges. Home-based tDCS offers a potential solution that improves accessibility; however, careful standardisation is required to ensure safe and effective application. We present a case of schizophrenia, where add-on home-based tDCS was administered based on a standard operating procedure (SOP) developed to address challenges unique to home administration, like device-related factors, patient and caregiver-related factors, and comprehensive caregiver training protocol. As a part of training, caregivers underwent observational learning, mannequin-based training for electrode placement, and assisted live-patient sessions. Pre and post-training competency assessments were done to ensure proficiency and safe administration. Over ten days, home-based tDCS sustained improvements in AVH without adverse effects. This case report supports the feasibility of home-based tDCS and provides a detailed SOP for implementing a safe and effective home-based tDCS treatment regime. This comprehensive SOP with a training protocol is notedly efficient for enhancing the accessibility and affordability of tDCS treatment protocols., Competing Interests: Declaration of Competing Interest There are no potential conflicts of interest to report., (Copyright © 2024 Elsevier B.V. All rights reserved.)

One of the major questions in high-density transcranial electrical stimulation (TES) is: given a region of interest (ROI) and electric current limits for safety, how much current should be delivered by each electrode for optimal targeting of the ROI? Several solutions, apparently unrelated, have been independently proposed depending on how “optimality” is defined and on how this optimization problem is stated mathematically. The least squares (LS), weighted LS (WLS), or reciprocity-based approaches are the simplest ones and have closed-form solutions. An extended optimization problem can be stated as follows: maximize the directional intensity at the ROI, limit the electric fields at the non-ROI, and constrain total injected current and current per electrode for safety. This problem requires iterative convex or linear optimization solvers. We theoretically prove in this work that the LS, WLS and reciprocity-based closed-form solutions are specific solutions to the extended directional maximization optimization problem. Moreover, the LS/WLS and reciprocity-based solutions are the two extreme cases of the intensity-focality trade-off, emerging under variation of a unique parameter of the extended directional maximization problem, the imposed constraint to the electric fields at the non-ROI. We validate and illustrate these findings with simulations on an atlas head model. The unified approach we present here allows a better understanding of the nature of the TES optimization problem and helps in the development of advanced and more effective targeting strategies.

Objectives: Top-down stress regulation, important for military operational performance and mental health, involves emotional working memory and the dorsolateral prefrontal cortex (DLPFC). Multisession transcranial direct current stimulation (tDCS) applied over the DLPFC during working memory training has been shown to improve working memory performance. This study tested the hypothesis that combined tDCS with working memory training also improves top-down stress regulation. However, tDCS response differs between individuals. Resting-state electrophysiological brain activity was post hoc explored as a possible predictor of tDCS response. The predictive value of the ratio between slow-wave theta oscillations and fast-wave beta oscillations (theta/beta ratio) was examined, together with the previously identified tDCS response predictors age, education, and baseline working memory performance., Materials and Methods: Healthy military service members (n = 79) underwent three sessions of real or sham tDCS over the right DLPFC (anode: F4, cathode: behind C2) at 2 mA for 20 minutes during emotional working memory training (N-back task). At baseline and within a week after the tDCS training sessions, stress regulation was assessed by fear-potentiated startle responses and subjective fear in a threat-of-shock paradigm with instructed emotional downregulation. Results were analyzed in generalized linear mixed-effects models., Results: Threat-of-shock responses and emotional working memory performance showed no significant group-level effects of the real vs sham tDCS training intervention (p > 0.07). In contrast, when considering baseline theta/beta ratios or the other tDCS response predictors, exploratory results showed a trait-dependent beneficial effect of tDCS on emotional working memory training performance during the first session (p < 0.01)., Conclusions: No evidence was found for effectivity of the tDCS training intervention to improve stress regulation in healthy military personnel. The emotional working memory training results emphasize the importance of studying the effects of tDCS in relation to individual differences., Clinical Trial Registration: This study was preregistered on September 16, 2019, at the Netherlands Trial Register (www.trialregister.nl) with ID: NL8028., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Corticobasal syndrome (CBS) is an atypical parkinsonian disorder that involves degeneration of brain regions associated with motor coordination and sensory processing. Combining transcranial direct current stimulation (tDCS) with rehabilitation training has been shown to improve upper-limb performance in other disease models. Here, we describe the protocol investigating whether tDCS with neurologic music therapy (NMT) (patterned sensory enhancement and therapeutic instrumental music performance) enhances functional arm/hand performance in individuals with CBS., Methods: Study participants are randomly assigned to six 30-min sessions (twice per week for 3 weeks) of NMT + either sham tDCS or active tDCS. We aim to stimulate the frontoparietal cortex, which is associated with movement execution/coordination and sensory processing. The hemisphere contralateral to the more affected arm is stimulated (total stimulation current of 2 mA from 5 dime-sized electrodes). Individualized NMT sessions designed to exercise the upper limb are provided. Participants undergo gross/fine motor, cognitive and emotional assessments at baseline and follow-up (one month after the final session). To investigate the immediate effects of tDCS and NMT training, gross /fine motor, affective level, and kinematic parameter measurements using motion sensors are collected before and after each session. Electroencephalography is used to collect electrical neurophysiological responses before, during, and after tDCS+NMT sessions. The study participants, neurologic music therapist and outcome assessor are blinded to whether participants are in the sham or active tDCS group., Conclusion: This noninvasive and patient-centered clinical trial for CBS may provide insight into rehabilitation options that are sorely lacking in this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

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

Objective: Performance accuracy and reaction time in cognitive tasks are routinely used to evaluate the efficacy of tDCS to affect cognitive task performance. tDCS alters the excitability of targeted brain areas and thereby alters performance of cognitive tasks. The drift diffusion model (DDM) provides some additional measures to explore information processing style, such as (non)decision time, bias for decision, and speed of information processing. DDM parameters are informative for the study of cognitive impairments in children with ADHD. In the present study, we aimed to evaluate the impact of tDCS on cognitive performance via DDM measures., Methods: This study conducted DDM modeling and reanalysis of two exploratory, single-blinded, within-subject design experiments, which were published earlier. In the first experiment, twenty- four children with ADHD performed a Go/ No- Go task during anodal or sham tDCS over the right dlPFC. In the second experiment, twenty- five children with ADHD performed the 1- back working memory task during anodal or sham tDCS over the left dlPFC. We reanalyzed the data after DDM modeling., Results: The conventional performance measures revealed no significant effect of tDCS on No- Go accuracy in the first experiment and 1-back accuracy in the second experiment. The 1-back reaction time and speed-accuracy tradeoff were however improved under the real stimulation condition. The DDM measures identified increased No-Go- bias and decision time with respect to inhibitory control, and an increased threshold and amount of information required for response in the 1- back test., Conclusion: In children with ADHD, anodal tDCS over the right dlPFC induces more conservative and less impulsive decisions. Furthermore, anodal tDCS over the left dlPFC enhanced efficacy of working memory performance with respect to agility and capacity. The experimental results show that drift diffusion modeling is useful for evaluation of the impact of tDCS on the style of information processing., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the effect of non-invasive neurostimulation therapies on dysphagia patients after stroke., Methods: We searched MEDLINE (Ovid), PubMed, Embase, Web of Science, ScienceDirect, and Cochrane library databases until April 22, 2020. All published and unpublished randomized controlled trials (RCT) were included. Full texts were independently reviewed. The risk of RCT bias was evaluated by two independent assessors using the Cochrane risk of bias tool. The primary outcome measure was swallowing function before and after neurostimulation therapy. The effect sizes are calculated from the extracted data and combined into a comprehensive summary statistic., Result: A total of 27 randomized controlled trials were included in this study, involving 914 stroke patients (27 intervention groups and 20 control groups). Meta-analysis showed that compared with the control group, noninvasive neurostimulation therapies (repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), surface neuromuscular electrical stimulation (sNMES) or pharyngeal electrical stimulation (PES)) had a better effect (SMD = 0.91; 95% CI: 0.54-1.27; Z = 4.84; P < 0.00001; I² = 86%). In the subgroup analysis based on type of stimulus, rTMS appeared to perform better. In the subgroup analysis based on clinical phase, stimulation applied in the acute phase may be more effective. In the subgroup analysis based on the site of injury, the brainstem injury group seemed to achieve better outcomes. In the subgroup analysis based on stroke type, the cerebral infarction group had better outcomes than the cerebral infarction/hemorrhage mixed group., Conclusions: Non-invasive neurostimulation therapies can effectively promote the recovery of dysphagia after stroke., (Copyright © 2021. Published by Elsevier Masson SAS.)

Prior neuroimaging and neurophysiological studies have found that the right posterior parietal cortex (PPC) plays an important role in mental rotation ability. Transcranial direct-current stimulation (tDCS) has been shown the potential to enhance cognitive ability by delivering a low current to the brain cortex of interest, via electrodes on the scalp. Here, we tested whether stimulating the PPC with tDCS can improve three-dimensional mental rotation performance and narrow gender difference. The classic three-dimensional Shepard-Metzler task was measured after three stimulation conditions (right PPC, left PPC, sham stimulation). The results indicated that stimulating the right PPC induced an improvement in accuracy and response time of mental rotation relative to sham stimulation. Stimulating the left PPC caused an enhancement in the accuracy but not in the response time. Gender difference during mental rotation was diminished after stimulation. These findings indicated that the PPC regions played a causal role in mental rotation ability. tDCS could be used as a promising non-invasive method to improve mental rotation skills in individuals with lower ability and to provide an effective therapeutic tool for neurological disorder rehabilitation., (Copyright © 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Objectives: The aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia., Methods: Thirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment., Results: For the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028)., Discussion: With the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objectives: A proposed replay of memory traces between the hippocampus and frontal cortical brain areas during sleep is of high relevance for overnight memory consolidation. Recently, we demonstrated that bi-frontal anodal transcranial direct current stimulation (tDCS) prior to sleep increases waking EEG gamma power and decreases total sleep time during the night. It is unclear whether this effect on cortical excitability has an influence on overnight memory consolidation. We hypothesized that bi-frontal evening tDCS interferes with overnight memory consolidation with a polarity specific impairment following anodal tDCS., Materials and Methods: Nineteen healthy participants underwent a within-subject, repeated-measures protocol in the sleep laboratory with bi-frontal tDCS applied prior to sleep according to the experimental protocol (anodal, cathodal, sham stimulation). Memory tasks for declarative and procedural memory were assessed prior to tDCS and on the following morning., Results: No deterioration of overnight memory consolidation following evening offline bi-frontal tDCS could be detected., Conclusion(s): The application of tDCS can be considered safe regarding overnight memory consolidation and represents a promising treatment approach in conditions of decreased vigilance and arousal., (© 2020 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC. on behalf of International Neuromodulation Society.)

Objective: Research suggests that the combination of different non-invasive brain stimulation techniques, such as intermittent theta-burst stimulation (iTBS) and transcranial direct current stimulation (tDCS), could enhance the effects of stimulation. Studies investigating the combination of tDCS and iTBS over the dorsolateral prefrontal cortex (DLPFC) are lacking. In this within-subjects study, we evaluated the additive effects of iTBS with tDCS on psychophysiological measures of stress., Method: Sixty-eight healthy individuals were submitted to a bifrontal tDCS + iTBS and sham tDCS + iTBS protocol targeting the DLPFC with a one-week interval. The Maastricht Acute Stress Test was used to activate the stress system after stimulation. Stress reactivity and recovery were assessed using physiological and self-report measures., Results: The stressor evoked significant psychophysiological changes in both stimulation conditions. However, no evidence was found for differences between them in stress reactivity and recovery. Participants reported more pain and feelings of discomfort to the bifrontal tDCS + iTBS protocol., Conclusion: In this study set-up, iTBS plus tDCS was not superior to iTBS in downregulating stress in healthy subjects., Significance: There is no evidence for an effect of combined tDCS-iTBS of the DLPFC on stress according to the parameters employed in our study. Future studies should explore other stimulation parameters, additive approaches and/or neurobiological markers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Transcranial Direct Current Stimulation (tDCS) aims to induce cortical plasticity by modulating the activity of brain structures. The broad stimulation pattern, which is one of the main limitations of tDCS, can be overcome with the recently developed technique called High-Definition tDCS (HD-tDCS)., Objective: Investigation of the effect of HD-tDCS on tinnitus in a large patient cohort., Methods: This prospective study included 117 patients with chronic, subjective, non-pulsatile tinnitus who received six sessions of anodal HD-tDCS of the right Dorsolateral Prefrontal Cortex (DLPFC). Therapy effects were assessed by use of a set of standardized tinnitus questionnaires filled out at the pre-therapy (T pre ), post-therapy (T 3w ) and follow-up visit (T 10w ). Besides collecting the questionnaire data, the perceived effect (i.e., self-report) was also documented at T 10w ., Results: The Tinnitus Functional Index (TFI) and Tinnitus Questionnaire (TQ) total scores improved significantly over time (p TFI <0.01; p TQ <0.01), with the following significant post hoc comparisons: T pre vs. T 10w (p TFI <0.05; p TQ <0.05) and T 3w vs. T 10w (p TFI <0.01; p TQ <0.01). The percentage of patients reporting an improvement of their tinnitus at T 10w was 47%. Further analysis revealed a significant effect of gender with female patients showing a larger improvement on the TFI and TQ (p TFI <0.01; p TQ <0.05)., Conclusions: The current study reported the effects of HD-tDCS in a large tinnitus population. HD-tDCS of the right DLPFC resulted in a significant improvement of the tinnitus perception, with a larger improvement for the female tinnitus patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Despite growing interest in underlying cognitive mechanisms of self-esteem, its neurocognitive correlates are not fully-understood. Attention bias to self-related stimuli is an example of self-referential processing (SRP) and its association with self-esteem is not well-studied. Moreover, previous studies showed that the medial prefrontal regions are involved in SRP which might suggest its involvement in self-esteem too. We investigated attentional bias to self-related stimuli and its association with the level of self-esteem in the first study (N = 30). In the second study (N = 15), we modulated activity of the ventromedial prefrontal cortex (VMPFC), as one of the medial prefrontal regions, using transcranial direct current stimulation (tDCS) to see how it affects different domains of self-esteem. Results showed that individuals with a higher level of self-esteem have more attentional bias to their own facial pictures (compared to other-facial pictures) and self-related words (compared to self-unrelated words) suggesting an impact of self-esteem on attentional and perceptual processes. Additionally, modulating activity of the VMPFC with 2 mA anodal and cathodal tDCS was associated with significantly higher ratings of global and total self-esteem but not other self-esteem domains. Our findings provide supporting evidence of neurocognitive correlates of self-esteem indicating a biasing influence of self-esteem on attention toward "self" and suggesting self-esteem as a function of SRP at behavioural and neural levels., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. MAN is a member of the Scientific Advisory Board of Neuroelectrics and NeuroDevice., (Copyright © 2019 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.)

Introduction: tDCS can modulate reading which is processed by lexical (ventral) and sub-lexical (dorsal) pathways. Previous research indicates that pathway recruitment in bilinguals depends on a script's orthographic depth and a reader's proficiency with it. The effect of tDCS on each reading pathway has not been investigated in bilinguals. We stimulated the left dorsal and ventral pathways separately in Chinese-English (C-E) bilinguals to understand whether pathway-specific modulation by tDCS is possible and, if so, how it is influenced by orthographic depth and script proficiency., Methods: A double-blind, sham-controlled, within-subject experiment was designed wherein 16 balanced bilinguals received anodal tDCS in dorsal, ventral and sham sessions. Two tDCS montages of electrode sizes 5 × 5 cm 2 with 1) anode at CP5 and cathode at CZ, and 2) anode at TP7 and cathode at nape of the neck, were applied for stimulating the dorsal and ventral pathways respectively. Bilinguals were asked to read word lists for each language before and after stimulation. RTs for accurate trials were analysed using linear mixed-effect modelling that included proficiency scores for reading English pseudo-words (PW) and Chinese pinyin., Results: For both languages, word reading RTs were faster following dorsal pathway stimulation. The dorsal stimulation effect (change in RT) was negatively correlated with pseudoword reading and pinyin proficiency. Stimulation of the ventral pathway decreased RTs only for Chinese reading., Conclusion: Dorsal and ventral reading pathways can be selectively modulated by tDCS in bilingual readers with dorsal (sub-lexical) pathway stimulation affecting reading in both scripts and ventral (lexical) pathway stimulation selectively affecting Chinese reading. Dorsal pathway tDCS effects are modulated by sub-lexical reading proficiency., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: This systematic review and meta-analysis aims to examine the effects of transcranial direct current stimulation (tDCS) on clinical symptoms in schizophrenia., Methods: A literature search was performed for articles published in English using the following databases: MEDLINE, EMBASE, PsycINFO, INSPEC, the Cumulative Index to Nursing & Allied Health Literature Plus (CINAHL Plus), AMED, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, EU Clinical Trials Register, and WHO International Clinical Trials Registry Platform, from their inception to October 2019. The primary outcome variables were the clinical symptoms of schizophrenia including positive symptoms, negative symptoms, and auditory hallucinations., Results: 16 randomized controlled trials (RCTs) were included in the meta-analysis, with a sample of 326 patients with active and with 310 sham tDCS. Active tDCS was found to be more effective in improving positive symptoms [standardized mean difference (SMD) = 0.17; 95 % confidence interval (CI) 0.001 to 0.33], negative symptoms [SMD = 0.43, 95 % CI 0.11, 0.75] and auditory hallucinations [SMD = 0.36 95 % CI 0.02, 0.70]. Subgroup analyses showed better results in cases of pure diagnosis of schizophrenia, higher frequency and more sessions of stimulation., Conclusion: tDCS was effective in improving positive symptoms, negative symptoms and auditory hallucination in schizophrenia. It therefore has potential as a safe and well-tolerated adjunctive intervention for schizophrenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)