Noninvasive modulation of human corticostriatal activity.

Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.

Action video games and posterior parietal cortex neuromodulation enhance both attention and reading in adults with developmental dyslexia.

The impact of action video games on reading performance has been already demonstrated in individuals with and without neurodevelopmental disorders. The combination of action video games and posterior parietal cortex neuromodulation by a transcranial random noise stimulation could enhance brain plasticity, improving attentional control and reading skills also in adults with developmental dyslexia. In a double blind randomized controlled trial, 20 young adult nonaction video game players with developmental dyslexia were trained for 15 h with action video games. Half of the participants were stimulated with bilateral transcranial random noise stimulation on the posterior parietal cortex during the action video game training, whereas the others were in the placebo (i.e. sham) condition. Word text reading, pseudowords decoding, and temporal attention (attentional blink), as well as electroencephalographic activity during the attentional blink, were measured before and after the training. The action video game + transcranial random noise stimulation group showed temporal attention, word text reading, and pseudoword decoding enhancements and P300 amplitude brain potential changes. The enhancement in temporal attention performance was related with the efficiency in pseudoword decoding improvement. Our results demonstrate that the combination of action video game training with parietal neuromodulation increases the efficiency of visual attention deployment, probably reshaping goal-directed and stimulus-driven fronto-parietal attentional networks interplay in young adults with neurodevelopmental conditions.

Transcranial stimulation of alpha oscillations up-regulates the default mode network.

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, in combination with simultaneous electroencephalography and functional MRI (EEG-fMRI), we demonstrated that α-tACS (versus Sham control) not only augmented EEG alpha oscillations but also strengthened fMRI and (source-level) alpha connectivity within the core of the DMN. Importantly, increase in alpha oscillations mediated the DMN connectivity enhancement. These findings thus identify a mechanistic link between alpha oscillations and DMN functioning. That transcranial alpha modulation can up-regulate the DMN further highlights an effective noninvasive intervention to normalize DMN functioning in various disorders.

Dopamine Alters the Effect of Brain Stimulation on Decision-Making.

Noninvasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS), show promise in treating a range of psychiatric and neurologic conditions. However, optimization of such applications requires a better understanding of how tDCS alters cognition and behavior. Existing evidence implicates dopamine in tDCS alterations of brain activity and plasticity; however, there is as yet no causal evidence for a role of dopamine in tDCS effects on cognition and behavior. Here, in a preregistered, double-blinded study, we examined how pharmacologically manipulating dopamine altered the effect of tDCS on the speed-accuracy trade-off, which taps ubiquitous strategic operations. Cathodal tDCS was delivered over the left prefrontal cortex and the superior medial frontal cortex before participants (N = 62, 24 males, 38 females) completed a dot-motion task, making judgments on the direction of a field of moving dots under instructions to emphasize speed, accuracy, or both. We leveraged computational modeling to uncover how our interventions altered latent decisional processes driving the speed-accuracy trade-off. We show that dopamine in combination with tDCS (but not tDCS alone nor dopamine alone) not only impaired decision accuracy but also impaired discriminability, which suggests that these manipulations altered the encoding or representation of discriminative evidence. This is, to the best of our knowledge, the first direct evidence implicating dopamine in the way tDCS affects cognition and behavior.SIGNIFICANCE STATEMENT tDCS can improve cognitive and behavioral impairments in clinical conditions; however, a better understanding of its mechanisms is required to optimize future clinical applications. Here, using a pharmacological approach to manipulate brain dopamine levels in healthy adults, we demonstrate a role for dopamine in the effects of tDCS in the speed-accuracy trade-off, a strategic cognitive process ubiquitous in many contexts. In doing so, we provide direct evidence implicating dopamine in the way tDCS affects cognition and behavior.

Lateralization of self-control over the dorsolateral prefrontal cortex in decision-making: a systematic review and meta-analytic evidence from noninvasive brain stimulation.

The dorsolateral prefrontal cortex (DLPFC) has been widely recognized as a crucial brain "control area." Recently, its causal role in promoting deliberate decision-making through self-control and the asymmetric performance of the left and right DLPFC in control functions have attracted the interest of many researchers. This study was designed to investigate the role of DLPFC in decision-making behaviors and lateralization of its control function by systematically examining the effects of noninvasive brain stimulation (NIBS) over the DLPFC on intertemporal choice, risk decision-making, and social fairness-related decision-making tasks. Literature searches were implemented at PubMed, Embase, Cochrane, Web of Science, Wanfang Data, China Science and Technology Journal Database, and China National Knowledge Infrastructure until May 10, 2022. Meta-analytic results for included studies were estimated by random-effect models. A total of 33 eligible studies were identified, yielding 130 effect sizes. Our results indicated that compared to sham group, excitatory NIBS over the left DLPFC reduced delay discounting rate (standardized mean differences, SMD = -0.51; 95% confidence interval, 95% CI: [-0.81, -0.21]) and risk-taking performance (SMD = -0.39, 95% CI [-0.68, -0.10]), and inhibitory NIBS over the right DLPFC increased self-interested choice of unfair offers (SMD = 0.50, 95% CI [0.04, 0.97]). Finding of current work indicated that neural excitement of the DLPFC activation improve individuals' self-control during decision-makings, whereas neural inhibition results in impaired control. In addition, our analyses furnish causal evidence for the presence of functional lateralization in the left and right DLPFC in monetary impulsive decision-making and social decision-making, respectively.

Use of transcranial magnetic stimulation (TMS) for studying cognitive control in depressed patients: A systematic review.

Major depressive disorder (MDD) is a debilitating mental disorder and the leading cause of disease burden. Major depressive disorder is associated with emotional impairment and cognitive deficit. Cognitive control, which is the ability to use perceptions, knowledge, and information about goals and motivations to shape the selection of goal-directed actions or thoughts, is a primary function of the prefrontal cortex (PFC). Psychotropic medications are one of the main treatments for MDD, but they are not effective for all patients. An alternative treatment is transcranial magnetic stimulation (TMS). Previous studies have provided mixed results on the cognitive-enhancing effects of TMS treatment in patients with MDD. Some studies have found significant improvement, while others have not. There is a lack of understanding of the specific effects of different TMS protocols and stimulation parameters on cognitive control in MDD. Thus, this review aims to synthesize the effectiveness of the TMS methods and a qualitative assessment of their potential benefits in improving cognitive functioning in patients with MDD. We reviewed 21 studies in which participants underwent a treatment of any transcranial magnetic stimulation protocol, such as repetitive TMS or theta-burst stimulation. One of the primary outcome measures was any change in the cognitive control process. Overall, the findings indicate that transcranial magnetic stimulation (TMS) may enhance cognitive function in patients with MDD. Most of the reviewed studies supported the notion of cognitive improvement following TMS treatment. Notably, improvements were predominantly observed in inhibition, attention, set shifting/flexibility, and memory domains. However, fewer significant improvements were detected in evaluations of visuospatial function and recognition, executive function, phonemic fluency, and speed of information processing. This review found evidence supporting the use of TMS as a treatment for cognitive deficits in patients with MDD. The results are promising, but further research is needed to clarify the specific TMS protocol and stimulation locations that are most effective.

Audiovisual gamma stimulation for the treatment of neurodegeneration.

Alzheimer's disease (AD) is the most common type of neurodegenerative disease and a health challenge with major social and economic consequences. In this review, we discuss the therapeutic potential of gamma stimulation in treating AD and delve into the possible mechanisms responsible for its positive effects. Recent studies reveal that it is feasible and safe to induce 40 Hz brain activity in AD patients through a range of 40 Hz multisensory and noninvasive electrical or magnetic stimulation methods. Although research into the clinical potential of these interventions is still in its nascent stages, these studies suggest that 40 Hz stimulation can yield beneficial effects on brain function, disease pathology, and cognitive function in individuals with AD. Specifically, we discuss studies involving 40 Hz light, auditory, and vibrotactile stimulation, as well as noninvasive techniques such as transcranial alternating current stimulation and transcranial magnetic stimulation. The precise mechanisms underpinning the beneficial effects of gamma stimulation in AD are not yet fully elucidated, but preclinical studies have provided relevant insights. We discuss preclinical evidence related to both neuronal and nonneuronal mechanisms that may be involved, touching upon the relevance of interneurons, neuropeptides, and specific synaptic mechanisms in translating gamma stimulation into widespread neuronal activity within the brain. We also explore the roles of microglia, astrocytes, and the vasculature in mediating the beneficial effects of gamma stimulation on brain function. Lastly, we examine upcoming clinical trials and contemplate the potential future applications of gamma stimulation in the management of neurodegenerative disorders.

tDCS of right-hemispheric Wernicke's area homologue affects contextual learning of novel lexicon.

Numerous studies have shown robust evidence of the right hemisphere's involvement in the language function, for instance in the processing of intonation, grammar, word meanings, metaphors, etc. However, its role in lexicon acquisition remains obscure. We applied transcranial direct current stimulation (tDCS) over the right-hemispheric homologue of Wernicke's area to assess its putative involvement in the processing of different types of novel semantics. After receiving 15 min of anodal, cathodal, or sham (placebo) tDCS, three groups of healthy participants learnt novel concrete and abstract words in the context of short stories. Learning outcomes were assessed using a battery of tests immediately after this contextual learning session and 24 h later. As a result, an inhibitory effect of cathodal tDCS and a facilitatory effect of anodal tDCS were found for abstract word acquisition only. We also found a significant drop in task performance on the second day of the assessment for both word types in all the stimulation groups, suggesting no significant influence of tDCS on the post-learning consolidation of new memory traces. The results suggest an involvement of Wernicke's right-hemispheric counterpart in initial encoding (but not consolidation) of abstract semantics, which may be explained either by the right hemispheres direct role in processing lexical semantics or by an indirect impact of tDCS on contralateral (left-hemispheric) cortical areas through cross-callosal connections.

Hand functioning in progressive multiple sclerosis improves with tDCS added to daily exercises: A home-based randomized, double-blinded, sham-controlled clinical trial.

BACKGROUND: Many individuals with progressive multiple sclerosis (PMS) are challenged by reduced manual dexterity and limited rehabilitation options. Transcranial direct current stimulation (tDCS) during motor training can improve rehabilitation outcomes. We developed a protocol for remotely supervising tDCS to deliver sessions of stimulation paired with training at home. OBJECTIVE: This study evaluated the effectiveness of at-home tDCS paired with manual dexterity training for individuals with PMS. METHODS: Sixty-five right-hand dominant participants with PMS and hand impairment were randomized to receive either active or sham M1-SO tDCS paired with manual dexterity training over 4 weeks. Clinical outcomes were measured by the changes in Nine-Hole Peg Test (9-HPT) and Dellon-Modified-Moberg-Pick-Up Test (DMMPUT). RESULTS: The intervention had high rates of adherence and completion (98% of participants completed at least 18 of 20 sessions). The active tDCS group demonstrated significant improvement for the left hand compared with baseline in 9-HPT (-5.85 ± 6.19 vs -4.23 ± 4.34, p = 0.049) and DMMPUT (-10.62 ± 8.46 vs -8.97 ± 6.18, p = 0.049). The active tDCS group reported improvements in multiple sclerosis (MS)-related quality of life (mean increase: 5.93 ± 13.04 vs -0.05 ± -8.27; p = 0.04). CONCLUSION: At-home tDCS paired with manual dexterity training is effective for individuals with PMS, with M1-SO tDCS enhancing training outcomes and offering a promising intervention for improving and preserving hand dexterity.

The effects of bilateral posterior parietal cortex tRNS on reading performance.

According to established cognitive neuroscience knowledge based on studies on disabled and typically developing readers, reading is based on a dual-stream model in which a phonological-dorsal stream (left temporo-parietal and inferior frontal areas) processes unfamiliar words and pseudowords, whereas an orthographic-ventral stream (left occipito-temporal and inferior frontal areas) processes known words. However, correlational neuroimaging, causal longitudinal, training, and pharmacological studies have suggested the critical role of visuo-spatial attention in reading development. In a double blind, crossover within-subjects experiment, we manipulated the neuromodulatory effect of a short-term bilateral stimulation of posterior parietal cortex (PPC) by using active and sham tRNS during reading tasks in a large sample of young adults. In contrast to the dual-stream model predicting either no effect or a selective effect on the stimulated phonological-dorsal stream (as well as to a general multisensory effect on both reading streams), we found that only word-reading performance improved after active bilateral PPC tRNS. These findings demonstrate a direct neural connectivity between the PPC, controlling visuo-spatial attention, and the ventral stream for visual word recognition. These results support a neurobiological model of reading where performance of the orthographic-ventral stream is boosted by an efficient deployment of visuo-spatial attention from bilateral PPC stimulation.

Combined noninvasive brain stimulation virtual reality for upper limb rehabilitation poststroke: A systematic review of randomized controlled trials.

Upper limb impairments are common consequences of stroke. Noninvasive brain stimulation (NIBS) and virtual reality (VR) play crucial roles in improving upper limb function poststroke. This review aims to evaluate the effects of combined NIBS and VR interventions on upper limb function post-stroke and to provide recommendations for future studies in the rehabilitation field. PubMed, MEDLINE, PEDro, SCOPUS, REHABDATA, EMBASE, and Web of Science were searched from inception to November 2023. Randomized controlled trials (RCTs) encompassed patients with a confirmed stroke diagnosis, administrated combined NIBS and VR compared with passive (i.e., rest) or active (conventional therapy), and included at least one outcome assessing upper limb function (i.e., strength, spasticity, function) were selected. The quality of the included studies was assessed using the Cochrane Collaboration tool. Seven studies met the eligibility criteria. In total, 303 stroke survivors (Mean age: 61.74 years) were included in this review. According to the Cochrane Collaboration tool, five studies were classified as "high quality," while two were categorized as "moderate quality". There are mixed findings for the effects of combined NIBS and VR on upper limb function in stroke survivors. The evidence for the effects of combined transcranial direct current stimulation and VR on upper limb function post-stroke is promising. However, the evidence regarding the effects of combined repetitive transcranial magnetic stimulation and VR on upper limb function is limited. Further randomized controlled trials with long-term follow-up are strongly warranted.

Comparative efficacy of different noninvasive brain stimulation protocols on upper-extremity motor function and activities of daily living after stroke: a systematic review and network meta-analysis.

The objectives of the study were to systematically evaluate the rehabilitation effect of noninvasive brain stimulation (NIBS) on upper extremity motor function and activities of daily living in stroke patients and to prioritize various stimulation protocols for reliable evidence-based medical recommendations in patients with upper extremity motor dysfunction after stroke. Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and CBM were searched to collect all randomized controlled trials (RCTs) of NIBS to improve upper extremity motor function in stroke patients. The retrieval time was from the establishment of all databases to May 2023. According to the Cochrane system evaluation manual, the quality of the included studies was evaluated, and the data were extracted. Statistical analysis was carried out by using RevMan 5.3, R 4.3.0, and Stata 17.0 software. Finally, 94 RCTs were included, with a total of 5546 patients. Meta-analysis showed that NIBS improved the Fugl-Meyer assessment (FMA) score (mean difference (MD) = 6.51, 95% CI 6.20 ~ 6.82, P < 0.05), MBI score (MD = 7.69, 95% CI 6.57 ~ 8.81, P < 0.05), ARAT score (MD = 5.06, 95% CI 3.85 ~ 6.27, P < 0.05), and motor evoked potential (MEP) amplitude. The modified Ashworth scale score (MD = - 0.37, 95% CI - 0.60 to - 0.14, P < 0.05), National Institutes of Health Stroke Scale score (MD = - 2.17, 95% CI - 3.32 to - 1.11, P < 0.05), incubation period of MEP (MD = - 0.72, 95% CI - 1.06 to - 0.38, P < 0.05), and central motor conduction time (MD = - 0.90, 95% CI - 1.29 to - 0.50, P < 0.05) were decreased in stroke patients. Network meta-analysis showed that the order of interventions in improving FMA scores from high to low was anodal-transcranial direct current stimulation (tDCS) (surface under the cumulative ranking curve (SUCRA) = 83.7%) > cathodal-tDCS (SUCRA = 80.2%) > high-frequency (HF)-repetitive transcranial magnetic stimulation (rTMS) (SUCRA = 68.5%) > low-frequency (LF)-rTMS (SUCRA = 66.5%) > continuous theta burst stimulation (cTBS) (SUCRA = 54.2%) > bilateral-tDCS (SUCRA = 45.2%) > intermittent theta burst stimulation (iTBS) (SUCRA = 34.1%) > sham-NIBS (SUCRA = 16.0%) > CR (SUCRA = 1.6%). In terms of improving MBI scores, the order from high to low was anodal-tDCS (SUCRA = 88.7%) > cathodal-tDCS (SUCRA = 85.4%) > HF-rTMS (SUCRA = 63.4%) > bilateral-tDCS (SUCRA = 56.0%) > LF-rTMS (SUCRA = 54.2%) > iTBS (SUCRA = 32.4%) > sham-NIBS (SUCRA = 13.8%) > CR (SUCRA = 6.1%). NIBS can effectively improve upper extremity motor function and activities of daily living after stroke. Among the various NIBS protocols, anodal-tDCS demonstrated the most significant intervention effect, followed by cathodal-tDCS and HF-rTMS.

Effects of Transcranial Direct Current Stimulation on Cognitive Function in Older Adults with and without Mild Cognitive Impairment: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Noninvasive brain stimulation (NIBS) has shown benefits for cognitive function in older adults. However, the effects of transcranial direct current stimulation (tDCS) on cognitive function in older adults are inconsistent across studies, and the evidence for tDCS has limitations. We aim to explore whether tDCS can improve cognitive function and different cognitive domains (i.e., learning and memory and executive function) in adults aged 65 years and older with and without mild cognitive impairment and to further analyze the influencing factors of tDCS. METHODS: Five English databases (PubMed, Cochrane Library, EMBASE, Web of Science, the cumulative Index to Nursing and Allied Health Literature [CINAHL]) and four Chinese databases were searched from inception to October 14, 2023. Literature screening, data extraction, and quality assessment were completed independently by two reviewers. All statistical analyses were conducted using RevMan software (version 5.3). Standardized mean difference (SMD) along with a 95% confidence interval (CI) was used to express the effect size of the outcomes, and a random-effect model was also used. RESULTS: A total of 10 RCTs and 1,761 participants were included in the meta-analysis, and the risk of bias in those studies was relatively low. A significant effect favoring tDCS on immediate postintervention cognitive function (SMD = 0.16, Z = 2.36, p = 0.02) was found. However, the effects on immediate postintervention learning and memory (SMD = 0.20, Z = 2.00, p = 0.05) and executive function (SMD = 0.10, Z = 1.22, p = 0.22), and 1-month postintervention cognitive function (SMD = 0.12, Z = 1.50, p = 0.13), learning and memory (SMD = 0.17, Z = 1.39, p = 0.16), and executive function (SMD = 0.08, Z = 0.67, p = 0.51) were not statistically significant. CONCLUSION: tDCS can significantly improve the immediate postintervention cognitive function of healthy older adults and MCI elderly individuals. Additional longitudinal extensive sample studies are required to clarify the specific effects of tDCS on different cognitive domains, and the optimal tDCS parameters need to be explored to guide clinical practice.

Noninvasive intervention by transcranial ultrasound stimulation: Modulation of neural circuits and its clinical perspectives.

Low-intensity focused transcranial ultrasound stimulation (TUS) is an emerging noninvasive technique capable of stimulating both the cerebral cortex and deep brain structures with high spatial precision. This method is recognized for its potential to comprehensively perturb various brain regions, enabling the modulation of neural circuits, in a manner not achievable through conventional magnetic or electrical brain stimulation techniques. The underlying mechanisms of neuromodulation are based on a phenomenon where mechanical waves of ultrasound kinetically interact with neurons, specifically affecting neuronal membranes and mechanosensitive channels. This interaction induces alterations in the excitability of neurons within the stimulated region. In this review, we briefly present the fundamental principles of ultrasound physics and the physiological mechanisms of TUS neuromodulation. We explain the experimental apparatus and procedures for TUS in humans. Due to the focality, the integration of various methods, including magnetic resonance imaging and magnetic resonance-guided neuronavigation systems, is important to perform TUS experiments for precise targeting. We then review the current state of the literature on TUS neuromodulation, with a particular focus on human subjects, targeting both the cerebral cortex and deep subcortical structures. Finally, we outline future perspectives of TUS in clinical applications in psychiatric and neurological fields.

Efficacy of Noninvasive Brain Stimulation in Treating General Psychopathology Symptoms in Schizophrenia: A Meta-Analysis.

OBJECTIVES: Noninvasive brain stimulation (NIBS) has been shown to effectively alleviate negative and positive symptoms in patients with schizophrenia. However, its impact on depressive symptoms and general psychopathology symptoms (GPSs), which are crucial for functional outcomes, remains uncertain. We aimed to compare the efficacy of various NIBS interventions in treating depressive symptoms and GPSs. METHODS: We conducted a comprehensive search of multiple databases and performed a meta-analysis to evaluate the efficacy of NIBS in treating depressive symptoms and GPSs in schizophrenia. The effect sizes of NIBS for depression symptoms and GPSs were estimated using standard mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses were employed to examine potential influencing factors on the pooled SMD of NIBS for GPSs. RESULTS: Our search yielded 35 randomized controlled trials involving 1715 individuals diagnosed with schizophrenia. The protocol of this systematic review was registered with INPLASY (protocol ID: INPLASY202320082). Neither repetitive transcranial magnetic stimulation (rTMS) nor transcranial direct current stimulation (tDCS) demonstrated significant improvements in depressive symptoms compared to sham controls. NIBS exhibited a small-to-moderate effect size for GPSs, with a pooled SMD of -0.2956 (95% CI: -0.459 to -0.132) and a heterogeneity (I2) of 58.9% (95% CI: 41.5% to 71.1%; p < 0.01) based on a random-effects model. Subgroup analyses of different types of NIBS, different frequencies of rTMS, and different stimulation sites of rTMS revealed no significant differences. Only sex had a significant influence on the effect size of NIBS for general psychopathology symptoms (p < 0.05). However, rTMS might be superior to tDCS, and high-frequency rTMS outperformed low-frequency rTMS in treating GPSs. CONCLUSIONS: We found a small-to-moderate effect size of NIBS in alleviating GPSs in patients with schizophrenia. Both rTMS and tDCS were more effective than sham stimulation in reducing GPSs in schizophrenia. The frequency used was associated with rTMS efficacy for GPSs.

Single Session Effects of Prolonged Continuous Theta Burst Stimulation Targeting Two Brain Regions on Pain Perception in Patients with Painful Diabetic Neuropathy: A Preliminary Study.

BACKGROUND: Painful diabetic neuropathy (pDN) is the most common cause of neuropathic pain (NP) in the United States. Prolonged continuous theta burst stimulation (pcTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is quick (1-4 minutes) and tolerable for most individuals, compared to high frequency rTMS and can modulate pain thresholds in healthy participants. However, its effects on patients with chronic pain are still unclear. The primary purpose of this preliminary study is to investigate the effects of single session pcTBS targeted at the primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) on a set of self-report measures of pain (SRMP) that assess the (a) sensory-discriminative; (b) affective-motivational; and (c) cognitive-evaluative aspects of pain experience. METHODS: For this prospective, single-blind study, forty-two participants with pDN were randomized to receive either pcTBS targeting the M1 or the DLPFC brain regions. SRMP were completed at baseline, post pcTBS and 24h-post pcTBS. A two-way mixed model repeated measures analysis of variance (2 brain regions by 3 time points) was conducted to evaluate the effects of pcTBS stimulation at M1 and DLPFC for each subscale of each SRMP. RESULTS: After a single session of pcTBS targeted at M1 or DLPFC in patients with pDN, statistically significant improvements from baseline to post pcTBS and baseline to 24 h-post pcTBS were observed for different SRMP subscales examining the (a) sensory-discriminative, (b) affective-motivational and (c) cognitive-evaluative components of the pain experience. At 24 h-post pcTBS, none of the participants reported any serious adverse events to the pcTBS treatment, thus demonstrating its feasibility. CONCLUSIONS: In pDN patients with NP, our study results demonstrated significant improvement in scores on self-report measures of pain (SRMP) after a single session of pcTBS targeting the M1 and DLPFC brain regions. Future studies should consider utilizing multiple sessions of pcTBS to evaluate its long-term effects on pain perception, safety and tolerability in patients with chronic pain. CLINICAL TRIAL REGISTRATION: This study was registered on the ClinicalTrials.gov website (NCT04988321).

No Frequency-Specific Effect of Transcranial Random Noise Stimulation on Resting EEG.

BACKGROUND: Transcranial random noise stimulation (tRNS) is a form of noninvasive transcranial electrical stimulation that applies alternating current in various randomized frequencies to the cortex, thereby improving cognitive functioning in multiple domains. However, the precise mechanism of tRNS, as well as its impact on human electroencephalography (EEG), remains unclear. This is partly because most studies have used tRNS in conjunction with a cognitive task, making it difficult to tease apart whether the observed changes in EEG are a result of tRNS, the cognitive task, or their interaction. METHODS: Forty-nine healthy individuals participated in this study and were randomly assigned to active tRNS (n = 24) and sham (n = 25) groups. tRNS was delivered for 20 minutes over Fp1/Fp2 and Oz. Resting-state EEG data were collected before and after either tRNS or sham stimulation. RESULTS: Cluster-based permutation tests using FieldTrip revealed no frequency-specific effect of tRNS on resting-state EEG data across four frequency bands (theta, alpha, beta, gamma). CONCLUSIONS: These observations suggest that tRNS itself does not target or alter specific EEG frequencies. Rather, tRNS most likely interacts with the cognitive task/activity at hand to produce an observable difference in post-tRNS EEG. Positive tRNS-EEG findings from previous studies are also likely to have resulted from the interactive and cognitive activity-dependent nature of tRNS.

Impact of the combination of virtual reality and noninvasive brain stimulation on the upper limb motor function of stroke patients: a systematic review and meta-analysis.

BACKGROUND: Stroke frequently results in upper limb motor dysfunction, with traditional therapies often failing to yield sufficient improvements. Emerging technologies such as virtual reality (VR) and noninvasive brain stimulation (NIBS) present promising new rehabilitation possibilities. OBJECTIVES: This study systematically reviews and meta-analyses the effectiveness of VR and NIBS in improving upper limb motor function in stroke patients. METHODS: Registered with PROSPERO (CRD42023494220) and adhering to the PRISMA guidelines, this study conducted a thorough search of databases including PubMed, MEDLINE, PEDro, REHABDATA, EMBASE, Web of Science, Cochrane, CNKI, Wanfang, and VIP from 2000 to December 1, 2023, to identify relevant studies. The inclusion criterion was stroke patients receiving combined VR and NIBS treatment, while exclusion criteria were studies with incomplete articles and data. The risk of bias was assessed using the Cochrane Collaboration tool. Statistical analysis was performed using Stata SE 15.0, employing either a fixed-effects model or a random-effects model based on the level of heterogeneity. RESULTS: A total of 11 studies involving 493 participants were included, showing a significant improvement in Fugl-Meyer Assessment Upper Extremity (FMA-UE) scores in the combined treatment group compared to the control group (SMD = 0.85, 95% CI [0.40, 1.31], p = 0.017). The Modified Ashworth Scale (MAS) scores significantly decreased (SMD = - 0.51, 95% CI [- 0.83, - 0.20], p = 0.032), the Modified Barthel Index (MBI) scores significantly increased (SMD = 0.97, 95% CI [0.76, 1.17], p = 0.004), and the Wolf Motor Function Test (WMFT) scores also significantly increased (SMD = 0.36, 95% CI [0.08, 0.64], p = 0.021). Subgroup analysis indicated that the duration of treatment influenced the outcomes in daily living activities. CONCLUSIONS: The combination of VR and NIBS demonstrates significant improvements in upper limb motor function in stroke patients. The duration of treatment plays a critical role in influencing the outcomes, particularly in activities of daily living. This systematic review has limitations, including language bias, unclear randomization descriptions, potential study omissions, and insufficient follow-up periods. Future studies should focus on exploring long-term effects and optimizing treatment duration to maximize the benefits of combined VR and NIBS therapy.

The efficacy of transcranial random noise stimulation in treating tinnitus: a systematic review.

PURPOSE: This review aims to examine the effects of transcranial random noise stimulation (tRNS) on tinnitus and to determine the optimal treatment parameters, if possible. METHODS: A comprehensive search, including MEDLINE, PubMed, EMBASE, CINAHL, SCOPUS, and PEDro, was conducted to determine experiments studying the effects of tRNS on tinnitus from inception to March 1, 2024. The Physiotherapy Evidence Database (PEDro) scale was used to evaluate the quality of the included studies. RESULTS: Seven studies met the eligibility criteria. A total of 616 patients with non-pulsatile tinnitus (mean age 50.93 years; 66% males) were included in this review. The included studies ranged from 3 to 8 out of 10 (median = 7) on the PEDro scale. The results showed that tRNS is an effective intervention in reducing tinnitus symptoms. CONCLUSIONS: The evidence for the effects of tRNS on people with chronic non-pulsatile tinnitus is promising. Administering tRNS with an intensity of 1-2 mA, high-frequency (101-650 Hz), using a 35 cm² electrode size over the auditory cortex and DLPFC, for 20 min with eight sessions may demonstrate the desired tRNS effects. The tRNS stimulation should be contralateral for unilateral tinnitus and bilaterally for bilateral tinnitus. Combining tRNS with other concurrent interventions may show superior effects in reducing tinnitus compared to tRNS alone. Further high-quality studies with larger sample sizes are strongly needed.

Reflecting the causes of variability of EEG responses elicited by cerebellar TMS.

Recently, Fong et al. published EEG responses in cerebral cortex elicited by cerebellar TMS (cbTMS) (Fong et al., 2023), which differ from our recently identified cbTMS-EEG responses (Gassmann et al., 2022). Fong et al. argued that this discrepancy is due to coil placement unsuitable for eliciting cerebellar brain inhibition (CBI) in our study. However, we reliably elicited CBI in our subjects. Consequently, this leads to a compelling discussion on possible reasons for the observed discrepancies in cbTMS-evoked EEG responses. Reliably measuring cbTMS-evoked EEG responses could become an important neurophysiological tool to test effective cerebellum-to-cortex connectivity.