Use Of Non-invasive Brain Stimulation Research Articles

Molecular Changes in the Ischemic Brain as Non-Invasive Brain Stimulation Targets—TMS and tDCS Mechanisms, Therapeutic Challenges, and Combination Therapies

Ischemic stroke is one of the leading causes of death and disability. As the currently used neurorehabilitation methods present several limitations, the ongoing research focuses on the use of non-invasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). NIBS methods were demonstrated to modulate neural excitability and improve motor and cognitive functioning in neurodegenerative diseases. However, their mechanisms of action are not fully elucidated, and the clinical outcomes are often unpredictable. This review explores the molecular processes underlying the effects of TMS and tDCS in stroke rehabilitation, including oxidative stress reduction, cell death, stimulation of neurogenesis, and neuroprotective phenotypes of glial cells. A highlight is put on the newly emerging therapeutic targets, such as ferroptotic and pyroptotic pathways. In addition, the issue of interindividual variability is discussed, and the role of neuroimaging techniques is investigated to get closer to personalized medicine. Furthermore, translational challenges of NIBS techniques are analyzed, and limitations of current clinical trials are investigated. The paper concludes with suggestions for further neurorehabilitation stroke treatment, putting the focus on combination and personalized therapies, as well as novel protocols of brain stimulation techniques.

Non-invasive brain stimulation in craving disorders: evidence-based umbrella review

INTRODUCTION: The use of brain stimulation in the control of craving disorders is controversial, mainly in relation to the best target, technique, duration, frequency and parameters. Several meta-analyses have been published, and their data should be summarized to support the best evidence-based clinical practice. OBJECTIVE: To provide the best level of evidence for the use of non-invasive brain stimulation (NIBS) in the control of craving disorders. METHODS: Umbrella review registraded on Prospero (CRD42021239577), and conducted according to PRISMA recommendations. The methodological quality and evidence level were assessed through AMSTAR, AMSTAR rank and GRADE. RESULTS: A total of 81 meta-analyses were screened and the final analysis was made on 10 studies including 224 randomized clinical trials (RCTs) enrolling 5,555 patients. The main targets of stimulation were the right, left and bi-hemispheric dorsolateral prefrontal cortices. The studies used anodal tDCS, and high-frequency rTMS. The protocols with the larger effect sizes were anodal tDCS with 2mA, for 30 minutes over the right DLPFC (g=0.45; 95%CI 0.328-0.583; p<0.001), and high-frequency rTMS (10Hz), with 100% of the resting motor threshold, over the left DLPFC (g=1.116; 95%CI 0.597-1.634; p<0.001). The quality of evidence ranged from very low to moderate because of inconsistencies mainly due to sample heterogeneity. CONCLUSION: The results of 10 meta-analyses assessing the efficacy of NIBS in the control of craving disorders are robust regarding the effect sizes and provide evidence that bi-hemispheric tDCS and high-frequency rTMS over the DLPFC are effective in the control of craving disorders. However, the evidence level is from low to moderate.

Understanding the effects of cortical gyrification in tACS: insights from experiments and computational models.

The alpha rhythm is often associated with relaxed wakefulness or idling and is altered by various factors. Abnormalities in the alpha rhythm have been linked to several neurological and psychiatric disorders, including Alzheimer's disease. Transcranial alternating current stimulation (tACS) has been proposed as a potential tool to restore a disrupted alpha rhythm in the brain by stimulating at the individual alpha frequency (IAF), although some research has produced contradictory results. In this study, we applied an IAF-tACS protocol over parieto-occipital areas to a sample of healthy subjects and measured its effects over the power spectra. Additionally, we used computational models to get a deeper understanding of the results observed in the experiment. Both experimental and numerical results showed an increase in alpha power of 8.02% with respect to the sham condition in a widespread set of regions in the cortex, excluding some expected parietal regions. This result could be partially explained by taking into account the orientation of the electric field with respect to the columnar structures of the cortex, showing that the gyrification in parietal regions could generate effects in opposite directions (hyper-/depolarization) at the same time in specific brain regions. Additionally, we used a network model of spiking neuronal populations to explore the effects that these opposite polarities could have on neural activity, and we found that the best predictor of alpha power was the average of the normal components of the electric field. To sum up, our study sheds light on the mechanisms underlying tACS brain activity modulation, using both empirical and computational approaches. Non-invasive brain stimulation techniques hold promise for treating brain disorders, but further research is needed to fully understand and control their effects on brain dynamics and cognition. Our findings contribute to this growing body of research and provide a foundation for future studies aimed at optimizing the use of non-invasive brain stimulation in clinical settings.

Transcranial direct current stimulation impairs updating of avoidance-based associative learning.

Exposure-based psychotherapies for the treatment of anxiety- and fear-based disorders rely on "corrective" associative learning. Namely the repeated confrontation with feared stimuli in the absence of negative outcomes allows the formation of new, corrected associations of safety, indicating that such stimuli no longer need to be avoided. Unfortunately, exposure-facilitated corrective learning tends to be bound by context and often poorly generalizes. One brain structure, the prefrontal cortex, is implicated in context-guided behavior and may be a relevant target for improving generalization of safety learning. Here, we tested whether inhibition of the left prefrontal cortex causally impaired updating of context-bound associations specifically or, alternatively, impaired updating of learned associations irrespective of contextual changes. Additionally, we tested whether prefrontal inhibition during corrective learning influenced subsequent generalization of associations to a novel context. In two separate experiments, participants received either 10 min of 2 mA cathodal transcranial direct current stimulation (tDCS) over EEG coordinate F3 (Experiment 1 n = 9, Experiment 2 n = 22) or sham stimulation (Experiment 1 n = 10, Experiment 2 n = 22) while previously learned associations were reversed in the same or a different context from initial learning. Next, to assess generalization of learning, participants were asked to indicate which of the previously seen images they preferred in a novel, never seen before context. Results indicate that tDCS significantly impaired reversal irrespective of context in Experiment 2 only. When taking learning rate across trials into account, both experiments suggest that participants who received sham had the greatest learning rate when reversal occurred in a different context, as expected, whereas participants who received active tDCS in this condition had the lowest learning rate. However, active tDCS was associated with preferring the originally disadvantageous, but then neural stimulus after stimulus after reversal occurred in a different context in Experiment 1 only. These results support a causal role for the left prefrontal cortex in the updating of avoidance-based associations and encourage further inquiry investigating the use of non-invasive brain stimulation on flexible updating of learned associations.

Effects of noninvasive brain stimulation on dual-task performance in different populations: A systematic review.

Increasing research has investigated the use of noninvasive brain stimulation (NIBS) on augmenting dual-task (DT) performance. To investigate the effects of NIBS on DT performance in different populations. Extensive electronic database search (from inception to November 20, 2022) was conducted in PubMed, Medline, Cochrane Library, Web of Science and CINAHL to identify randomized controlled trials (RCTs) that investigated the effects of NIBS on DT performance. Main outcomes were balance/mobility and cognitive function under both single-task (ST) and DT conditions. Fifteen RCTs were included, involving two types of intervention techniques: transcranial direct current stimulation (tDCS) (twelve RCTs) and repetitive transcranial magnetic stimulation (rTMS) (three RCTs); and four different population groups: healthy young adults, older adults, Parkinson's disease (PD), and stroke. For tDCS, under DT condition, significant improvement in speed was only observed in one PD and one stroke RCT, and stride time variability in one older adults RCT. Reduction in DTC in some gait parameters was demonstrated in one RCT. Only one RCT showed significant reduction in postural sway speed and area during standing under DT condition in young adults. For rTMS, significant improvements in fastest walking speed and time taken to Timed-up-and-go test under both ST and DT conditions were observed at follow-up in one PD RCT only. No significant effect on cognitive function in any RCT was observed. Both tDCS and rTMS showed promising effects in improving DT walking and balance performance in different populations, however, due to the large heterogeneity of included studies and insufficient data, any firm conclusion cannot be drawn at present.

Roy H Hamilton: Diversity, Equity, and Inclusion Editor

Roy H Hamilton, MD, MS, FAAN, who is one of two Associate Editors for Diversity, Equity, and Inclusion (DEI) for the Neurology® journals, published by the American Academy of Neurology.1 He is also professor of Neurology, Psychiatry, and Physical Medicine & Rehabilitation at Penn and Vice Chair of Diversity and Inclusion for the Department of Neurology. In this interview with Science Editor, Dr Hamilton discusses his role with the Neurology® journals as a DEI Editor focusing on broadening the definition of expert peer review and helping ensure that the journals use best publishing practices related to unbiased research and reporting. Science Editor: Tell us about your job and organization. How did you get involved in an editorial role? Dr Roy Hamilton: I’ve been involved in the American Academy of Neurology (AAN) for many years since I was a medical student, and I have benefited greatly from AAN programs. I received scholarships to meetings, participated in AAN’s Diversity Leadership Program, and advanced in my career as a recipient of a clinical training research fellowship. I’ve held a number of administrative roles at Penn related to diversity, equity, and inclusion, where I also run a research lab focused on the use of non-invasive brain stimulation (transcranial magnetic stimulation [TMS]) and transcranial electrical stimulation (tES) in neurology. As a researcher, I understand the peer-review process and was already engaged in editorial leadership activities for other journals and had knowledge of the scientific literature, so it seemed a logical step to move into the […]

Application of Transcranial Direct Current Stimulation in Sleep Disturbances

Sleep disturbances are common across all age groups, and they encompass a broad range of impairments of daytime functioning and comorbid various clinical conditions. However, current treatment methods for sleep disturbances have several limitations. As the ‘top-down’ pathway is known to play an important role in sleep-wake regulation, and as neuronal activity abnormalities have been reported as a potential pathological mechanism of sleep disturbances, the use of non-invasive brain stimulation—such as transcranial direct current stimulation (tDCS) in treating sleep disturbances—has emerged. In the present review, we first explain the mechanism of tDCS, and we also introduce recent studies that have applied tDCS to sleep disorders, along with other sleep-related tDCS studies. In conclusion, many studies have achieved improvements in sleep state, although some of these studies have reported inconsistent effects of tDCS according to the protocol and the conditions used. Further studies are needed to explore the optimal protocols to use when applying tDCS in each sleep disturbance and to enhance the evidence on the clinical efficacy of tDCS.

Application of non-invasive brain stimulation with the use of repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in the treatment of dysphagia following an ischemic stroke – analysis of research reports

Stroke is one of the significant problems and causes of death, in particular in highly developed countries. It is also the most common cause of dysphagia. This study is devoted to the analysis of publications from the last decade concerning research on the use of non-invasive brain stimulation (TMS, tDCS) in the treatment of dysphagia following an ischemic stroke. The following databases were searched for publications: PUBMED, Polish Scientific Journals Database, EBSCO, ScienceDirect. Out of 358 articles found, only two met all the inclusion conditions. The studies discussed in this article included patients who had their first unilateral ischemic stroke, followed by dysphagia. Findings from pilot studies on the effectiveness of the use of tDCS in the treatment of dysphagia following an ischemic stroke were analysed. Fourteen patients aged 50-92 were randomly assigned to two groups. The study group was treated with anodic stimulation, and the control group with sham brain stimulation. The results showed that patients in the study group obtained a statistically significant result, indicating an improvement in the swallowing function as measured by the Dysphagia Score and Severity Scale. The above data may indicate the effectiveness of the use of tDCS in the treatment of dysphagia. Fifty patients were qualified for the research on the effectiveness of rTMS in the treatment of dysphagia. Three groups were created: the first group treated with high frequency rTMS, where patients received rTMS stimulation – 3Hz; the second group with low frequency rTMS – 1Hz; and the control group. The effectiveness of the therapy used was assessed on the fifth day and after 1, 2 and 3 months. After 5 days the groups where active rTMS stimulation was used showed greater improvement in the swallowing function compared to the sham stimulation group. Improved results in the Standardized Swallowing Assessment were also recorded after 3 months in the 1Hz and 3Hz groups, but this did not apply to the control group. In three groups, the results of the water swallow test and the degree of dysphagia improved after 3 months. This analysis shows that non-invasive brain stimulation using tDCS and rTMS in the treatment of dysphagia is associated with improved swallowing function. However, the small number of studies conducted in this area does not allow for extrapolation of their results.

Non-invasive brain stimulation for treating neurogenic dysarthria: A systematic review.

Although non-invasive central and peripheral stimulations are accruing support as promising treatments in different neurological conditions, their effects on dysarthria have not been systematically investigated. The purpose of this review was to examine the evidence base of non-invasive stimulation for treating dysarthria, identify which stimulation parameters have the most potential for treatment and determine safety risks. A systematic review with meta-analysis, when possible, involving publications indexed in MEDLINE, PsychINFO, EMBASE CINHAL the Linguistics and Language Behavioral Abstracts, Web of Science, Cochrane Register of Control Trials and 2 trial registries was completed. Articles were searched in December 2018 and updated in June 2021 using keywords related to brain and electrical stimulation, dysarthria and research design. We included trials with randomised, cross-over or quasi-experimental designs; involving a control group; and investigating treatment of neurogenic dysarthria with non-invasive stimulation. Methodological quality was determined with the Cochrane's Risk of Bias-2 tool. In total, 6186 studies were identified; 10 studies (6 randomised controlled trials and 4 cross-over studies) fulfilled the inclusion criteria. All 10 trials (268 adults with Parkinson's disease, stroke and neurodegenerative cerebellar ataxia) focused on brain stimulation (6 repetitive transcranial magnetic stimulation; 3 transcranial direct current stimulation; and 1 repetitive transorbital alternating current stimulation). Adjunct speech-language therapy was delivered in 2 trials. Most trials reported one or more positive effects of stimulation on dysarthria-related features; however, given the overall high risk of bias and heterogeneity in participant, trial and outcome measurement characteristics, no conclusions can be drawn. Post-treatment size effects for 2 stroke trials demonstrated no statistically significant differences between active and sham stimulation across 3 dysarthria outcomes. Evidence for use of non-invasive brain stimulation in treating dysarthria remains inconclusive. Research trials that provide reliable and replicable findings are required.

Recent advances in noninvasive brain stimulation for schizophrenia.

Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms. Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies. Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.

Memory Modulation Via Non-invasive Brain Stimulation: Status, Perspectives, and Ethical Issues.

While research to improve memory or counter decay caused by neurodegenerative diseases has a fairly long history, scientific attempts to erase memories are very recent. The use of non-invasive brain stimulation for memory modulation represents a new and promising application for the treatment of certain disorders [such as Post-Traumatic Stress Disorder (PTSD)]. However, numerous ethical issues are related to memory intervention. In particular, the possibility of using forms of non-invasive brain stimulation requires to distinguish treatment interventions from the enhancement of the healthy. Furthermore, a range of important societal and legal concerns arise when manipulating memories. In this short contribution, we address some of the most significant ethical, social, and legal implications surrounding the application of memory-modulation techniques and offer a series of reflections and considerations, which we hope can be of use to guide -and perhaps regulate- their potential, future implementation in society.

Integrating Non-Invasive Brain Stimulation Into the Undergraduate Psychology Curriculum: An Upper-Level Laboratory Course Using Transcranial Direct Current Stimulation

Background Psychology has seen a recent explosion in the use of non-invasive brain stimulation (NIBS) to understand cognition. The prevalence of techniques such as transcranial direct current stimulation (tDCS) in published research has grown immensely in the past decade; however, there has been little effort to incorporate these techniques into the undergraduate curriculum through course-based undergraduate research experiences (CUREs). Objective To demonstrate the feasibility of creating a CURE focused on tDCS and to offer practical advice on how to create one at other institutions. Method I present a novel undergraduate CURE focused on tDCS, as well as practical advice on how to teach about and safely implement student-driven tDCS experiments. Results Undergraduate students learned about and engaged first-hand in their own non-invasive brain stimulation research in an upper-level psychology laboratory course. Conclusion An undergraduate laboratory course that focuses on non-invasive brain stimulation has a range of potential benefits for students and instructors alike. Furthermore, it allows undergraduates to gain experience using a rapidly growing neuroscientific methodology. Teaching Implications Given that tDCS is a safe and relatively inexpensive method of modulating brain function, the present course demonstrates the ease, and potential advantages, of incorporating NIBS into the undergraduate psychology curriculum.

Noninvasive Brain Stimulation for Nicotine Dependence in Schizophrenia: A Mini Review.

Individuals with schizophrenia are 10 times more likely to have a tobacco use disorder than the general population. Up to 80% of those with schizophrenia smoke tobacco regularly, a prevalence three-times that of the general population. Despite the striking prevalence of tobacco use in schizophrenia, current treatments are not tailored to the pathophysiology of this population. There is growing support for use of noninvasive brain stimulation (NIBS) to treat substance use disorders (SUDs), particularly for tobacco use in neurotypical smokers. NIBS interventions targeting the dorsolateral prefrontal cortex have been effective for nicotine dependence in control populations—so much so that transcranial magnetic stimulation is now FDA-approved for smoking cessation. However, this has not borne out in the studies using this approach in schizophrenia. We performed a literature search to identify articles using NIBS for the treatment of nicotine dependence in people with schizophrenia, which identified six studies. These studies yielded mixed results. Is it possible that nicotine has a unique effect in schizophrenia that is different than its effect in neurotypical smokers? Individuals with schizophrenia may receive additional benefit from nicotine's pro-cognitive effects than control populations and may use nicotine to improve brain network abnormalities from their illness. Therefore, clinical trials of NIBS interventions should test a schizophrenia-specific target for smoking cessation. We propose a generalized approach whereby schizophrenia-specific brain circuitry related to SUDs is be identified and then targeted with NIBS interventions.

Cerebellar tDCS as Therapy for Cerebellar Ataxias.

In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques to influence cerebellar activity and the effects of cerebellar stimulation on other brain regions through its multiple complex projections. From the early 1990s, with the discovery of the so-called cerebellar inhibition (CBI), several studies have focused their attention on the use of cerebellar NIBS as treatment for different motor disorders. Cerebellar ataxias (CAs) represent the prototypical clinical manifestation of cerebellar alterations, but other movement disorders, such as Parkinson's disease, essential tremor, and dystonia have also been associated with alterations of networks which include the cerebellum, or of the cerebellum itself. Cerebellar transcranial direct current stimulation (ctDCS) could indeed represent an economical, non-invasive therapeutic tool with minimal side effects, thus improving the clinical management of patients and their quality of life. Studies show that ctDCS is effective as a therapeutic option for motor symptoms in patients with CAs, and especially in those with less severe forms, suggesting that ctDCS efficacy could result from augmented neuronal compensation, which itself relies on preserved cerebellar volume. Evidence for the efficacy of ctDCS is less conclusive for the other aforementioned motor disorders, although preliminary results are promising. Future studies should adopt more rigorous methods (e.g., larger sample sizes, double blinding, better characterization of the sample, reliable biomarkers), in order to allow the scientific community to derive higher-quality evidence on the efficacy of ctDCS as a therapeutic option for motor disorders.

Transcranial magnetic stimulation in animal models of neurodegeneration.

Brain stimulation techniques offer powerful means of modulating the physiology of specific neural structures. In recent years, non-invasive brain stimulation techniques, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation, have emerged as therapeutic tools for neurology and neuroscience. However, the possible repercussions of these techniques remain unclear, and there are few reports on the incisive recovery mechanisms through brain stimulation. Although several studies have recommended the use of non-invasive brain stimulation in clinical neuroscience, with a special emphasis on TMS, the suggested mechanisms of action have not been confirmed directly at the neural level. Insights into the neural mechanisms of non-invasive brain stimulation would unveil the strategies necessary to enhance the safety and efficacy of this progressive approach. Therefore, animal studies investigating the mechanisms of TMS-induced recovery at the neural level are crucial for the elaboration of non-invasive brain stimulation. Translational research done using animal models has several advantages and is able to investigate knowledge gaps by directly targeting neuronal levels. In this review, we have discussed the role of TMS in different animal models, the impact of animal studies on various disease states, and the findings regarding brain function of animal models after TMS in pharmacology research.

Participant Experiences of Transcranial Direct Current Stimulation (tDCS) as a Treatment for Antipsychotic Medication Induced Weight Gain.

Background: Despite the growing number of studies on the use of non-invasive brain stimulation in people with schizophrenia, there is limited research on participant views of such treatment methods.Aim: Explore participant experiences and perceptions of transcranial direct current stimulation (tDCS).Methods: Twelve people with schizophrenia took part in semi-structured interviews after having completed 5 sessions of tDCS. Thematic analysis was used to identify codes and themes.Results: Five themes were identified: (1) motivation for study enrolment; (2) concerns about tDCS; (3) factors reducing the fear of tDCS; (4) experience of tDCS; (5) perceived effects of tDCS.Conclusions: The study provides insight into the perceptions and experiences of each individual. Participants were concerned about the safety of tDCS and associated it with invasive procedures such as electroconvulsive therapy and lobotomy. Educational materials and a good relationship with the researcher played an important role in reducing the fear of brain stimulation. All participants described tDCS as uncomfortable, however, agreed that unpleasant sensations only lasted for a short while (20 s−5 min). After the first session, participants no longer felt anxious about the remaining ones. Strategies to improve treatment experience and study recruitment have been identified.

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Radiological society of North America: 106th annual meeting, November 29 to December 5, 2020

Cerebellar Direct Current Stimulation (ctDCS) in the Treatment of Huntington's Disease: A Pilot Study and a Short Review of the Literature.

Introduction: In recent years, a growing body of literature has investigated the use of non-invasive brain stimulation (NIBS) techniques as a putative treatment in Huntington's Disease (HD). Our aim was to evaluate the effects of cerebellar transcranial Direct Current Simulation (ctDCS) on the motor outcome in patients affected by HD, encompassing at the same time the current knowledge about the effects of NIBS both on motor and non-motor dysfunctions in HD.Materials and Methods: Four patients (two females) were enrolled and underwent ctDCS (both anodal or sham, elapsed by at least 3 months: 2.0 mA, 20 min per day, 5 days a week). Clinical scores were assessed by using the Unified Huntington's Disease Rating Scale – part I (UHDRS-I), immediately before ctDCS (T0), at the end of the 5-days treatment (T1) and 4 weeks later (T2).Results: Anodal ctDCS improved motor scores compared to baseline (p = 0.0046), whereas sham stimulation left them unchanged (p = 0.33, Friedman test). In particular, following anodal ctDCS, UHDRS-I score significantly improved, especially regarding the subitem “dystonia,” both at T1 and T2 compared to sham condition (p < 0.05; Wilcoxon matched-pairs signed test).Conclusions: ctDCS improved motor scores in HD, with effects lasting for about 4 weeks after tDCS completion. This is the first study discussing the putative role of cerebellar non-invasive simulation for the treatment of HD.

Determining the Efficacy of the Combined Use of Noninvasive Brain Stimulation (NIBS) and OT Interventions: A Scoping Review

Abstract Date Presented 03/27/20 This review examines the efficacy of NIBS coupled with OT interventions. Sixty studies utilizing OT along with NIBS were included. Results support the use of NIBS as an add-on to OT interventions. Identifying the efficacy of NIBS as an adjuvant to existing therapies assists in characterizing interventions that may be useful in those clinical populations in which high-intensity therapy is not tolerable or feasible. Primary Author and Speaker: Ghazala Saleem Additional Authors and Speakers: Carly Goldberg Contributing Authors: Stacy Suskauer

M70. THE EFFICACY OF COMBINING COGNITIVE REMEDIATION AND NON-INVASIVE BRAIN STIMULATION. A SYSTEMATIC REVIEW

BackgroundCognitive deficits are commonly observed in people diagnosed with schizophrenia and have been found to be more predictive of future daily and community functioning than the severity of clinical symptoms (e.g., hallucinations and delusions). Cognitive remediation (CR) is a psychological treatment developed to improve cognitive functioning and thereby daily functioning. Despite the effectivity of CR programs, reduced neuroplasticity in brain networks underlying the cognitive tasks may impede the effectiveness of these treatment programs. Increasing the neuroplasticity in these networks by the use of non-invasive brain stimulation (NIBS) like transcranial direct current stimulation or transcranial magnetic stimulation might boost the effect of CR. In a systematic review, we will address the question whether the combination of non-invasive brain stimulation and cognitive remediation may be a promising treatment strategy. We will apply a transdiagnostic perspective in order to determine the potential benefit of combining CR and NIBS in general, and not specific to a diagnostic category.MethodsA systematic review of literature was conducted by searching PsycINFO, Pubmed, Web of Science, and Medline databases for combined treatments of CR and NIBS. Included studies were assessed for cognitive, clinical and functional outcomes.Results64 studies were identified, with 40 studies including clinical populations (e.g., schizophrenia, Alzheimer’s disease, HIV, MS). The cognitive outcomes showed mixed results. Most effects were found on complex attention and executive functioning. In these domains about 38% of the studies found an added positive treatment effect for combining interventions, in comparison to single interventions (i.e. CR, NIBS, or CR+sham-stimulation). Functional outcome measures were included in ten of the 40 studies with clinical populations. Eight studies found a positive trend towards greater improvements in daily functioning when CR and NIBS were combined.DiscussionSo far, findings indicate promising effects of combining CR and NIBS on cognitive functioning and daily functioning in healthy and various clinical populations. There is a lot of variety between studies (e.g., duration of treatment, number of total sessions, number of weekly sessions, cognitive domains targeted) which may explain the mixed results. Especially, the design of the CR varied widely. Strategy-use and targeting meta-cognition, which were identified as effective elements of CR as a stand-alone treatment were not included in many combined CR+NIBS designs. Future studies have to elucidate whether the combining CR (including strategy-use and meta-cognition) and NIBS has an additive effect on cognitive and/or daily functioning compared to non-combined treatment. Moreover, future studies should evaluate whether beneficial effects from the experimental studies translate into long-term improvement in activities of daily life.