Attention improvement to transcranial alternating current stimulation at gamma frequency over the right frontoparietal network: a preliminary report.

Applying transcranial alternating current stimulation (tACS) at 40 Hz to the frontal and parietal regions, either unilaterally (left or right) or bilaterally, can improve cognitive dysfunctions. This study aimed to explore the influence of tACS at gamma frequency over right fronto-parietal (FP) region on attention. The analysis is based on retrospective data from a clinical intervention. We administered test of variables of attention (TOVA; visual mode) to 44 participants with various neuropsychiatric diagnoses before and after 12 sessions of tACS treatment. Alternating currents at 2.0 mA were delivered to the electrode positions F4 and P4, following the 10-20 EEG convention, for 20 mins in each session. We observed significant improvement across 3 indices of the TOVA, including reduction of variability in reaction time (p = 0.0002), increase in d-Prime (separability of targets and non-targets; p = 0.0157), and decrease in commission error rate (p = 0.0116). The mean RT and omission error rate largely remained unchanged. Artificial injection of tACS at 40 Hz over right FP network may improve attention function, especially in the domains of consistency in performance, target/non-target discrimination, and inhibitory control.

Multi-objective optimization via evolutionary algorithm (MOVEA) for high-definition transcranial electrical stimulation of the human brain.

Designing a transcranial electrical stimulation (tES) strategy requires considering multiple objectives, such as intensity in the target area, focality, stimulation depth, and avoidance zone. These objectives are often mutually exclusive. In this paper, we propose a general framework, called multi-objective optimization via evolutionary algorithm (MOVEA), which solves the non-convex optimization problem in designing tES strategies without a predefined direction. MOVEA enables simultaneous optimization of multiple targets through Pareto optimization, generating a Pareto front after a single run without manual weight adjustment and allowing easy expansion to more targets. This Pareto front consists of optimal solutions that meet various requirements while respecting trade-off relationships between conflicting objectives such as intensity and focality. MOVEA is versatile and suitable for both transcranial alternating current stimulation (tACS) and transcranial temporal interference stimulation (tTIS) based on high definition (HD) and two-pair systems. We comprehensively compared tACS and tTIS in terms of intensity, focality, and steerability for targets at different depths. Our findings reveal that tTIS enhances focality by reducing activated volume outside the target by 60%. HD-tTIS and HD-tDCS can achieve equivalent maximum intensities, surpassing those of two-pair tTIS, such as 0.51 V/m under HD-tACS/HD-tTIS and 0.42 V/m under two-pair tTIS for the motor area as a target. Analysis of variance in eight subjects highlights individual differences in both optimal stimulation policies and outcomes for tACS and tTIS, emphasizing the need for personalized stimulation protocols. These findings provide guidance for designing appropriate stimulation strategies for tACS and tTIS. MOVEA facilitates the optimization of tES based on specific objectives and constraints, advancing tTIS and tACS-based neuromodulation in understanding the causal relationship between brain regions and cognitive functions and treating diseases. The code for MOVEA is available at https://github.com/ncclabsustech/MOVEA.

Outcome measures for electric field modeling in tES and TMS: A systematic review and large-scale modeling study.

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.

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.

Non-Invasive Brain Stimulation Does Not Improve Working Memory in Schizophrenia: A Meta-Analysis of Randomised Controlled Trials.

Poor working memory functioning is commonly found in schizophrenia. A number of studies have now tested whether non-invasive brain stimulation can improve this aspect of cognitive functioning. This report used meta-analysis to synthesise the results of these studies to examine whether transcranial electrical stimulation (tES) or repetitive transcranial magnetic stimulation (rTMS) can improve working memory in schizophrenia. The studies included in this meta-analysis were sham-controlled, randomised controlled trials that utilised either tES or rTMS to treat working memory problems in schizophrenia. A total of 22 studies were included in the review. Nine studies administered rTMS and 13 administered tES. Meta-analysis revealed that compared to sham/placebo stimulation, neither TMS nor tES significantly improved working memory. This was found when working memory was measured with respect to the accuracy on working memory tasks (TMS studies: Hedges' g = 0.112, CI95: -0.082, 0.305, p = .257; tES studies Hedges' g = 0.080, CI95: -0.117, 0.277, p = .427) or the speed working memory tasks were completed (rTMS studies: Hedges' g = 0.233, CI95: -0.212, 0.678, p = .305; tES studies Hedges' g = -0.016, CI95: -0.204, 0.173, p = .871). For tES studies, meta-regression analysis found that studies with a larger number of stimulation sessions were associated with larger treatment effects. This association was not found for TMS studies. At present, rTMS and tES is not associated with a reliable improvement in working memory for individuals with schizophrenia.

Unification of optimal targeting methods in transcranial electrical stimulation.

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.

Enhancement of phonemic verbal fluency in multilingual young adults by transcranial random noise stimulation.

Several studies have analyzed the effects of transcranial direct current stimulation on verbal fluency tasks in non-clinical populations. Nevertheless, the reported effects on verbal fluency are inconsistent. In addition, the effect of other techniques such as transcranial random noise stimulation (tRNS) on verbal fluency enhancement has yet to be studied in healthy multilingual populations. This study aims to explore the effects of tRNS on verbal fluency in healthy multilingual individuals. Fifty healthy multilingual (Spanish, English and Basque) adults were randomly assigned to a tRNS or sham group. Electrodes were placed on the left dorsolateral prefrontal cortex and left inferior frontal gyrus. All participants performed phonemic and semantic verbal fluency tasks before, during (online assessment) and immediately after (offline assessment) stimulation in three different languages. The results showed significantly better performance by participants who received tRNS in the phonemic verbal fluency tasks in Spanish (in the online and offline assessment) and English (in the offline assessment). No differences between conditions were found in Basque nor semantic verbal fluency. These findings suggests that tRNS on the left prefrontal cortex could help improve phonemic, yet not semantic, fluency in healthy multilingual adults.

Modulation of Alcohol Use Disorder by Brain Stimulation.

Currently available therapeutic modalities for alcohol use disorder (AUD) produce limited effect sizes or long-term compliance. Recent methods that were developed to modulate brain activity represent potential novel treatment options. Various methods of brain stimulation, when applied repeatedly, can induce long-term neurobiological, behavioral, and cognitive modifications. Recent studies in alcoholic subjects indicate the potential of brain stimulation methods to reduce alcohol craving, consumption, and relapse. Specifically, deep brain stimulation (DBS) of the nucleus accumbens or non-surgical stimulation of the dorsolateral prefrontal cortex (PFC) or medial PFC and anterior cingulate cortex using transcranial magnetic stimulation (TMS) has shown clinical benefit. However, further preclinical and clinical research is needed to establish understanding of mechanisms and the treatment protocols of brain stimulation for AUD. While efforts to design comparable apparatus in rodents continue, preclinical studies can be used to examine targets for DBS protocols, or to administer temporal patterns of pulsus similar to those used for TMS, to more superficial targets through implanted electrodes. The clinical field will benefit from studies with larger sample sizes, higher numbers of stimulation sessions, maintenance sessions, and long follow-up periods. The effect of symptoms provocation before and during stimulation should be further studied. Larger studies may have the power to explore predictive factors for the clinical outcome and thereby to optimize patient selection and eventually even develop personalization of the stimulation parameters.

Tripod transcranial alternating current stimulation at 5-Hz to alleviate anxiety symptoms: A preliminary report.

INTRODUCTION: One of the most common applications of transcranial electrical stimulation (tES) at low current intensity is to induce a relaxed state or reduce anxiety. With technical advancement, different waveforms, montages, and parameters can be incorporated into the treatment regimen. We developed a novel protocol to treat individuals with anxiety disorders by transcranial alternating current stimulation (tACS). METHODS: A total of 27 individuals with anxiety disorders underwent tACS treatment for 12 sessions, with each session lasting 25 min. tACS at 5 Hz was applied to F4 (1.0 mA), P4 (1.0 mA), and T8 (2.0 mA) EEG lead positions (tripod), with sinewave oscillation between T8 and F4/P4. We evaluated the primary and secondary outcomes using the Beck Anxiety Inventory (BAI) and neuropsychological assessments. RESULTS: Of the 27 patients, 19 (70.4 %) experienced a reduction in symptom severity >50 %, with an average reduction of BAI 58.5 %. All reported side effects were mild, with itching or tingling being the most common complaint. No significant differences were noted in attention, linguistic working memory, visuospatial working memory, or long-term memory in neuropsychological assessments. CONCLUSION: The results suggest the potential of this novel tripod tACS design as a rapid anxiety alleviator and the importance of a clinical trial to verify its efficacy.

Lattice layout and optimizer effect analysis for generating optimal transcranial electrical stimulation (tES) montages through the metaheuristic L1L1 method.

Introduction: This study focuses on broadening the applicability of the metaheuristic L1-norm fitted and penalized (L1L1) optimization method in finding a current pattern for multichannel transcranial electrical stimulation (tES). The metaheuristic L1L1 optimization framework defines the tES montage via linear programming by maximizing or minimizing an objective function with respect to a pair of hyperparameters. Methods: In this study, we explore the computational performance and reliability of different optimization packages, algorithms, and search methods in combination with the L1L1 method. The solvers from Matlab R2020b, MOSEK 9.0, Gurobi Optimizer, CVX's SeDuMi 1.3.5, and SDPT3 4.0 were employed to produce feasible results through different linear programming techniques, including Interior-Point (IP), Primal-Simplex (PS), and Dual-Simplex (DS) methods. To solve the metaheuristic optimization task of L1L1, we implement an exhaustive and recursive search along with a well-known heuristic direct search as a reference algorithm. Results: Based on our results, and the given optimization task, Gurobi's IP was, overall, the preferable choice among Interior-Point while MOSEK's PS and DS packages were in the case of Simplex methods. These methods provided substantial computational time efficiency for solving the L1L1 method regardless of the applied search method. Discussion: While the best-performing solvers show that the L1L1 method is suitable for maximizing either focality and intensity, a few of these solvers could not find a bipolar configuration. Part of the discrepancies between these methods can be explained by a different sensitivity with respect to parameter variation or the resolution of the lattice provided.

Alpha transcranial alternating current stimulation as add-on to neglect training: a randomized trial.

Visuospatial neglect is a common and debilitating condition following unilateral stroke, significantly impacting cognitive functioning and daily life. There is an urgent need for effective treatments that can provide clinically relevant and sustained benefits. In addition to traditional stroke treatment, non-invasive brain stimulation, such as transcranial alternating current stimulation, shows promise as a complementary approach to enhance stroke recovery. In the current study, we aimed to evaluate the additive effects of multi-session transcranial alternating current stimulation at alpha frequency when combined with visual scanning training in chronic stroke patients with visuospatial neglect. In this double-blind randomized controlled trial, we compared the effects of active transcranial alternating current stimulation at alpha frequency to sham (placebo) transcranial alternating current stimulation, both combined with visual scanning training. Both groups received eighteen 40-minute training sessions over a 6-week period. A total of 22 chronic visuospatial neglect patients participated in the study (active group n = 12, sham group n = 10). The median age was 61.0 years, with a median time since stroke of 36.1 months. We assessed the patients at six time-points: at baseline, after the first, ninth and eighteenth training sessions, as well as 1 week and 3 months following the completion of the combined neuromodulation intervention. The primary outcome measure was the change in performance on a visual search task, specifically the star cancellation task. Secondary outcomes included performance on a visual detection task, two line bisection tasks and three tasks evaluating visuospatial neglect in daily living. We found significantly improved visual search (primary outcome) and visual detection performance in the neglected side in the active transcranial alternating current stimulation group, compared to the sham transcranial alternating current stimulation group. We did not observe stimulation effects on line bisection performance nor in daily living. Time effects were observed on all but one outcome measures. Multi-session transcranial alternating current stimulation combined with visual scanning training may be a more effective treatment for chronic visuospatial neglect than visual scanning training alone. These findings provide valuable insights into novel strategies for stroke recovery, even long after the injury, with the aim of enhancing cognitive rehabilitation outcomes and improving the overall quality of life for individuals affected by this condition. Trial registration: ClinicalTrials.gov; registration number: NCT05466487; https://clinicaltrials.gov/ct2/show/NCT05466487.

Neural consequences of 5-Hz transcranial alternating current stimulation over right hemisphere: An eLORETA EEG study.

INTRODUCTION: Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can effectively alleviate anxiety symptoms. This study aimed to explore the neural mechanisms that drive the therapeutic benefits. METHODS: We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after a tACS treatment session. tACS was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8 (10-10 EEG convention). With eLORETA, we transformed the scalp signals into the current source density in the cortex. We then assessed the differences between post- and pre-treatment brain maps across multiple spectra (delta to low gamma) with non-parametric statistics. RESULTS: We observed a trend of heightened power in alpha and reduced power in mid-to-high beta and low gamma, in accord with the EEG markers of anxiolytic effects reported in previous studies. Additionally, we observed a consistent trend of de-synchronization at the stimulating sites across spectra. CONCLUSION: tACS 5-Hz over the right hemisphere demonstrated EEG markers of anxiety reduction. The after-effects of tACS on the brain are intricate and cannot be explained solely by the widely circulated entrainment theory. Rather, our results support the involvement of plasticity mechanisms in the offline effects of tACS.

Effects of transcranial electrical stimulation techniques on foreign vocabulary learning.

Although the use of transcranial electrical stimulation (tES) techniques on healthy population has been linked to facilitating language learning, studies on their effects on foreign language learning processes are scarce and results remain unclear. The objective of this study was to analyze whether tES enhances foreign language learning processes. Sixty-four healthy native Spanish-speaking participants were randomly assigned to four groups (transcranial direct current, transcranial random noise, tDCS-tRNS stimulation, or sham). They completed two intervention sessions with a two-week gap in between. During the first session the participants received stimulation (1.5 mA) while learning new English words and then performed recall and recognition tasks. Learning was assessed at follow-up, two weeks later. No differences in learning between groups were observed in the first session (F(1,61)= .86; p = .36). At follow-up, significantly higher learning accuracy was observed after tRNS compared to sham (p = .037). These results suggest that tRNS could be helpful in improving the processes involved in foreign language vocabulary learning.

Multiple functions of the angular gyrus at high temporal resolution.

Here, the functions of the angular gyrus (AG) are evaluated in the light of current evidence from transcranial magnetic/electric stimulation (TMS/TES) and EEG/MEG studies. 65 TMS/TES and 52 EEG/MEG studies were examined in this review. TMS/TES literature points to a causal role in semantic processing, word and number processing, attention and visual search, self-guided movement, memory, and self-processing. EEG/MEG studies reported AG effects at latencies varying between 32 and 800 ms in a wide range of domains, with a high probability to detect an effect at 300-350 ms post-stimulus onset. A three-phase unifying model revolving around the process of sensemaking is then suggested: (1) early AG involvement in defining the current context, within the first 200 ms, with a bias toward the right hemisphere; (2) attention re-orientation and retrieval of relevant information within 200-500 ms; and (3) cross-modal integration at late latencies with a bias toward the left hemisphere. This sensemaking process can favour accuracy (e.g. for word and number processing) or plausibility (e.g. for comprehension and social cognition). Such functions of the AG depend on the status of other connected regions. The much-debated semantic role is also discussed as follows: (1) there is a strong TMS/TES evidence for a causal semantic role, (2) current EEG/MEG evidence is however weak, but (3) the existing arguments against a semantic role for the AG are not strong. Some outstanding questions for future research are proposed. This review recognizes that cracking the role(s) of the AG in cognition is possible only when its exact contributions within the default mode network are teased apart.

Stimulated brains and meditative minds: A systematic review on combining low intensity transcranial electrical stimulation and meditation in humans.

Background: Low intensity transcranial electrical stimulation (tES) and meditation are two promising, yet variable, non-pharmacological interventions. Growing research is investigating combined effects of both techniques on one's cognitive, emotional, and physical health. Objective: This article reviews the current research that combines tES and meditation interventions in healthy and diseased participants. The review considers the intervention parameters and their effects in a well-organized manner. Method: A systematic search for clinical and experimental published studies was conducted in the PubMed, Cochrane, and transcranial direct current stimulation (tDCS) databases using common keywords for tES and for meditation techniques well defined by previous studies. Unpublished ongoing studies were identified with the ClinicalTrials.gov and DRKS.de clinical trial websites. Results: 20 published studies and 13 ongoing studies were included for qualitative analysis. 13 published articles studied patients with chronic pain, psychological disorders, cognitive impairment, and movement disorders. Anodal tDCS was the only tES technique while mindfulness meditation was the most common meditation type. Eight studies had a main group effect, with outcome improvement in the active combined intervention. However, most published studies showed improvements after at least one combined intervention with variable effects. Conclusion: Pairing anodal tDCS with meditation shows promising improvements of the physical, mental, and emotional aspects of daily life. Further studies are required to confirm the relevance of this combination in the clinic.

Behavioral Validation of Individualized Low-Intensity Transcranial Electrical Stimulation (tES) Protocols.

Large interindividual variability in the effects of low-intensity transcranial electrical stimulation (tES) considerably limits its potential for clinical applications. It has been recently proposed that individualizing stimulation dose by accounting for interindividual anatomic differences would reduce the variability in electric fields (E-fields) over the targeted cortical site and therefore produce more consistent behavioral outcomes. However, improvement in behavioral outcomes following individualized dose tES has never been compared with that of conventional fixed dose tES. In this study, we aimed to empirically evaluate the effect of individualized dose tES on behavior and further compare it with the effects of sham and fixed dose stimulations. We conducted a single-blinded, sham-controlled, repeated-measures study to examine the impact of transcranial direct current stimulation on motor learning and that of transcranial alternating current stimulation on the working memory of 42 healthy adult individuals. Each participant underwent three sessions of tES, receiving fixed dose, individualized dose, or sham stimulation over the targeted brain region for the entire behavioral task. Our results showed that the individualized dose reduced the variability in E-fields at the targeted cortical surfaces. However, there was no significant effect of tES on behavioral outcomes. We argue that although the stimulation dose and E-field intensity at the targeted cortical site are linearly correlated, the effect of E-fields on behavior seems to be more complex. Effective optimization of tES protocols warrants further research considering both neuroanatomical and functional aspects of behavior.

Effects of Transcranial Electrical Stimulation on Gambling and Gaming: A Systematic Review of Studies on Healthy Controls, Participants with Gambling/Gaming Disorder, and Substance Use Disorder.

Gambling disorder (GD) and internet gaming disorder (IGD) are formally recognized behavioral addictions with a rapidly growing prevalence and limited treatment options. Recently, transcranial electrical stimulation (tES) techniques have emerged as potentially promising interventions for improving treatment outcomes by ameliorating cognitive functions implicated in addictive behaviors. To systematize the current state of evidence and better understand whether and how tES can influence gambling and gaming-related cognitive processes, we conducted a PRISMA-guided systematic review of the literature, focusing on tES effects on gaming and gambling in a diverse range of population samples, including healthy participants, participants with GD and IGD, as well as participants with substance abuse addictions. Following the literature search in three bibliographic databases (PubMed, Web of Science, and Scopus), 40 publications were included in this review, with 26 conducted on healthy participants, 6 focusing on GD and IGD patients, and 8 including participants with other addictions. Most of the studies targeted the dorsolateral prefrontal cortex, using transcranial direct current stimulation (tDCS), and assessed the effects on cognition, using gaming and gambling computerized cognitive tasks measuring risk taking and decision making, e.g., balloon analogue risk task, Iowa gambling task, Cambridge gambling task, etc. The results indicated that tES could change gambling and gaming task performances and positively influence GD and IGD symptoms, with 70% of studies showing neuromodulatory effects. However, the results varied considerably depending on the stimulation parameters, sample characteristics, as well as outcome measures used. We discuss the sources of this variability and provide further directions for the use of tES in the context of GD and IGD treatment.

Home-administered transcranial direct current stimulation with asynchronous remote supervision in the treatment of depression: feasibility, tolerability, and clinical effectiveness.

Introduction Background: Depression is an often chronic condition, characterized by wide-ranging physical, cognitive and psychosocial symptoms that can lead to disability, premature mortality or suicide. It affects 350 million people globally, yet up to 30% do not respond to traditional treatment, creating an urgent need for novel non-pharmacological treatments. This open-label naturalistic study assesses the practical feasibility, tolerability, and clinical effectiveness of home-administered transcranial direct current stimulation (tDCS) with asynchronous remote supervision, in the treatment of depression. Method: Over the course of 3 weeks, 40 patients with depression received psychotherapy and half of this group also received daily bi-frontal tDCS stimulation of the dorsolateral prefrontal cortex. These patients received tDCS for 30 min per session with the anode placed over F3 and the cathode over F4, at an intensity of 2 mA for 21 consecutive days. We measured patients' level of depression symptoms at four time points using the Beck Depression Inventory, before treatment and at 1-week intervals throughout the treatment period. We monitored practical feasibility such as daily protocol compliance and tolerability including side effects, with the PlatoScience cloud-based remote supervision platform. Results: Of the 20 patients in the tDCS group, 90% were able to comply with the protocol by not missing more than three of their assigned sessions, and none dropped out of the study. No serious adverse events were reported, with only 14 instances of mild to moderate side effects and two instances of scalp pain rated as severe, out of a total of 420 stimulation sessions. Patients in the tDCS group showed a significantly greater reduction in depression symptoms after 3 weeks of treatment, compared to the treatment as usual (TAU) group [t(57.2) = 2.268, p = 0.027]. The tDCS group also showed greater treatment response (50%) and depression remission rates (75%) compared to the TAU group (5 and 30%, respectively). Discussion Conclusion: These findings provide a possible indication of the clinical effectiveness of home-administered tDCS for the treatment of depression, and its feasibility and tolerability in combination with asynchronous supervision.

Multipair transcranial temporal interference stimulation for improved focalized stimulation of deep brain regions: A simulation study.

Temporal interference stimulation (TIS) has been proved to be effective in stimulating deep brain regions while avoiding the stimulation of neocortical regions in animal experiments. In the traditional TIS, two alternating currents are injected with different frequencies via two electrode pairs attached to the scalp. In the human brain, however, it is difficult to achieve a focal stimulation of deep brain structures due to the high complexity of human brain structures. In this study, we hypothesized that the use of multiple electrode pairs may contribute to the more focalized delivery of temporal interference (TI) currents to the target site in the deep area of the brain. Based on this hypothesis, we proposed a novel multipair TIS method that employs more than two electrode pairs for improved focalized stimulation of the deep brain region (in this study, the head of the right hippocampus). Three realistic finite element models were used to validate the feasibility of the proposed multipair TIS. Additional electrode pairs were sequentially added to the conventional two-electrode pairs with the aim of maximizing the delivery of TI currents to the target while minimizing TI currents in the neocortical regions. The results confirmed that the multipair TIS provides better focalized stimulation than the conventional two-pair TIS for all three head models. It is expected that the proposed multipair TIS can be used to enhance the effectiveness of noninvasive deep brain stimulation.

Novel Non-invasive Transcranial Electrical Stimulation for Parkinson's Disease.

Conventional transcranial electrical stimulation (tES) is a non-invasive method to modulate brain activity and has been extensively used in the treatment of Parkinson's disease (PD). Despite promising prospects, the efficacy of conventional tES in PD treatment is highly variable across different studies. Therefore, many have tried to optimize tES for an improved therapeutic efficacy by developing novel tES intervention strategies. Until now, these novel clinical interventions have not been discussed or reviewed in the context of PD therapy. In this review, we focused on the efficacy of these novel strategies in PD mitigation, classified them into three categories based on their distinct technical approach to circumvent conventional tES problems. The first category has novel stimulation modes to target different modulating mechanisms, expanding the rang of stimulation choices hence enabling the ability to modulate complex brain circuit or functional networks. The second category applies tES as a supplementary intervention for PD hence amplifies neurological or behavioral improvements. Lastly, the closed loop tES stimulation can provide self-adaptive individualized stimulation, which enables a more specialized intervention. In summary, these novel tES have validated potential in both alleviating PD symptoms and improving understanding of the pathophysiological mechanisms of PD. However, to assure wide clinical used of tES therapy for PD patients, further large-scale trials are required.