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Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer's disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma‐tACS on verbal long‐term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well‐tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials. We compared the effects of a single session online gamma‐rhythmic auditory stimulation (rAS) and temporal gamma‐transcranial alternating current stimulation (tACS) on memory processes in healthy individuals. Findings reveal that 40 Hz stimulation enhances verbal working memory (i.e., digit span backward score), while 60 Hz stimulation reduces immediate recall intrusions rate during a declarative long‐term memory task. These frequency‐specific effects suggest a potential role for auditory cortex activity in immediate cognitive demands, shedding light on the mechanisms of gamma frequency neuromodulation. [ABSTRACT FROM AUTHOR]

Non‐invasive brain stimulation techniques offer therapeutic potential for neurological and psychiatric disorders. However, current methods are often limited in their stimulation depth. The novel transcranial temporal interference stimulation (tTIS) aims to overcome this limitation by non‐invasively targeting deeper brain regions. In this study, we aimed to evaluate the efficacy of tTIS in modulating alpha activity during a mental rotation task. The effects of tTIS were compared with transcranial alternating current stimulation (tACS) and a sham control. Participants were randomly assigned to a tTIS, tACS, or sham group. They performed alternating blocks of resting and mental rotation tasks before, during, and after stimulation. During the stimulation blocks, participants received 20 min of stimulation adjusted to their individual alpha frequency (IAF). We assessed shifts in resting state alpha power, event‐related desynchronization (ERD) of alpha activity during mental rotation, as well as resulting improvements in behavioral performance. Our results indicate tTIS and tACS to be effective in modulating cortical alpha activity during mental rotation, leading to an increase in ERD from pre‐ to poststimulation as well as compared to sham stimulation. However, this increase in ERD was not correlated with enhanced mental rotation performance, and resting state alpha power remained unchanged. Our findings underscore the complex nature of tTIS and tACS efficacy, indicating that stimulation effects are more observable during active cognitive tasks, while their impacts are less pronounced on resting neuronal systems. Our study adds to the limited human research on the novel tTIS technique, which holds the potential for non‐invasive deep brain stimulation. We show that while tTIS and tACS can modulate cortical alpha activity during an active cognitive task, they do not improve behavioral performance or affect resting state alpha power. This underscores the task‐specific effectiveness of these techniques, suggesting their therapeutic potential is most effective during active cognitive engagement. [ABSTRACT FROM AUTHOR]

This review aims to demonstrate the connections between event-related potentials (ERPs), event-related oscillations (EROs), and non-invasive brain stimulation (NIBS), with a specific focus on transcranial alternating current stimulation (tACS). We begin with a short examination and discussion of the relation between ERPs and EROs. Then, we investigate the diverse fields of NIBS, highlighting tACS as a potent tool for modulating neural oscillations and influencing cognitive performance. Emphasizing the impact of tACS on individual ERP components, this article offers insights into the potential of conventional tACS for targeted stimulation of single ERP components. Furthermore, we review recent articles that explore a novel approach of tACS: ERP-aligned tACS. This innovative technique exploits the temporal precision of ERP components, aligning tACS with specific neural events to optimize stimulation effects and target the desired neural response. In conclusion, this review combines current knowledge to explore how ERPs, EROs, and NIBS interact, particularly highlighting the modulatory possibilities offered by tACS. The incorporation of ERP-aligned tACS introduces new opportunities for future research, advancing our understanding of the complex connection between neural oscillations and cognitive processes. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated changes in athletes brain imaging across a competitive season due to repeated head impacts during collision sports. However, there is no data reporting cortical activity in elite female rugby sevens players. There is scant literature on the effects of high-definition (HD)-transcranial direct current stimulation (tDCS) on cortical activity responses at different time points (TP) across the competitive season on the responsiveness of spectral band frequencies for HD-tDCS stimulation. This study examined the cortical activity of elite female rugby sevens players prior to pre-season (TP1) and following five months of training and competition (TP2), and the acute effects of HD-tDCS on cortical activity parameters. For each TP, the squad was randomly allocated to the HD-tDCS sham or the HD-tDCS anodal (active) stimulation groups. The Stroop task was performed for approximately 15 min prior to HD-tDCS (Stroop task-PRE). Following completion of the Stroop task-PRE, participants received 20-minutes of HD-tDCS stimulation and then performed the Stroop task (Stroop task-POST). A diminished responsiveness of cortical activity to the perturbation (HD-tDCS) for TP2 (vs. TP1) was observed, with cortical rhythms exhibiting a relative decline in faster bands (alpha, beta, and gamma), while slower bands (delta and theta) increased its proportional contribution to cortical activity. This discovery implies a potential alteration in the neural substrate's responsiveness to neuromodulation, likely influenced by the cumulative effects of repeated head impacts. The diminished responsiveness to HD-tDCS prompts significant considerations for the application of neuromodulation techniques in athletes participating in contact/collision sports. [ABSTRACT FROM AUTHOR]

Stroke is a major cause of death and disability among adults in China, and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation. The non-invasive brain stimulation (NBS) can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions, whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward. The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) are important methods of NBS. Their recovery principles, stimulation parameters, and clinical applications have been summarized. The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques. The future development trend and the key technical problems are expounded for the clinical applications. [ABSTRACT FROM AUTHOR]

Background/Objectives: Increasing evidence shows an involvement of brain plasticity mechanisms in both motor and central manifestations of neuromuscular disorders (NMDs). These mechanisms could be specifically addressed with neuromodulation or rehabilitation protocols. The aim of this scoping review is to summarise the evidence on plasticity mechanisms' involvement in NMDs to encourage future research. Methods: A scoping review was conducted searching the PubMed and Scopus electronic databases. We selected papers addressing brain plasticity and central nervous system (CNS) studies through non-invasive brain stimulation techniques in myopathies, muscular dystrophies, myositis and spinal muscular atrophy. Results: A total of 49 papers were selected for full-text examination. Regardless of the variety of pathogenetic and clinical characteristics of NMDs, studies show widespread changes in intracortical inhibition mechanisms, as well as disruptions in glutamatergic and GABAergic transmission, resulting in altered brain plasticity. Therapeutic interventions with neurostimulation techniques, despite being conducted only anecdotally or on small samples, show promising results; Conclusions: despite challenges posed by the rarity and heterogeneity of NMDs, recent evidence suggests that synaptic plasticity may play a role in the pathogenesis of various muscular diseases, affecting not only central symptoms but also strength and fatigue. Key questions remain unanswered about the role of plasticity and its potential as a therapeutic target. As disease-modifying therapies advance, understanding CNS involvement in NMDs could lead to more tailored treatments. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), and transcranial direct current stimulation (tDCS), is an emerging intervention that has been used to treat various mental illnesses. However, previous studies have not comprehensively compared the efficacies of various NIBS modalities in alleviating anxiety symptoms among patients with generalized anxiety disorder (GAD). Therefore, this study conducted a systematic review and meta-analysis to assess the efficacy of NIBS for patients with GAD. A systematic search of four major bibliographic databases (Embase, PubMed, Web of Science and The Cochrane Library) was conducted from inception dates to November 26, 2023 to identify eligible studies. The data were analyzed using a random-effects model. Seven randomized controlled trials (RCTs) were included in the meta-analysis. Significant differences were found in changes in Hamilton anxiety rating scale (HARS) scores, study-defined response, and remission between the intervention and control groups. Moreover, the intervention groups experienced a significantly higher frequency of headaches. The results revealed that interventions improved GAD compared to control groups. cTBS and rTMS exhibited better treatment efficacy than tDCS, which did not appear to have a significant therapeutic effect. Longer follow-up periods and larger sample sizes are required in future RCTs. This meta-analysis was conducted in accordance with PRISMA guidelines and registered at PROSPERO (https://www.crd.york.ac.uk/PROSPERO/ , CRD42023466285). • Systematic review and meta-analysis of NIBS techniques, including cTBS, rTMS, and tDCS, for treating GAD. • NIBS significantly reduces anxiety symptoms and improves response and remission rates. • The efficacy is notably contingent on the stimulation types employed. • Discerning headaches as an adverse event exhibited notable statistical disparities. [ABSTRACT FROM AUTHOR]

Background: Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain. Objective: We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately. Methods: We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1–3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia. Results: Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention. Conclusions: Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: In individuals with patellofemoral pain (PFP), addressing increased knee valgus during weight-bearing activities typically involves strengthening weak hip muscles. However, recent literature highlights the role of altered descending central control in abnormal movements associated with PFP. While transcranial direct current stimulation (tDCS) has demonstrated the capacity to enhance neuroplasticity, its application targeting the corticomotor function of gluteal muscles in PFP remains unexplored. This study aimed to investigate the effects of combining bimodal tDCS with exercise on frontal plane kinematics in individuals with PFP. The hypothesis was that bimodal tDCS, specifically targeting the corticomotor function of the gluteal muscles, would augment the effectiveness of exercise interventions in improving frontal plane kinematics compared to sham stimulation. Methods: Ten participants with PFP participated in two sessions involving either bimodal tDCS or sham stimulation, concurrently with hip strengthening exercises. Weight-bearing tasks, including single leg squat, single leg landing, single leg hopping, forward step-down, and lateral step-down, were performed and recorded before and after each session. Pain visual analog scale (VAS) scores were also documented. A one-way ANOVA with repeated measures was employed to compare kinematics, while a Friedman test was used to compare VAS across the three conditions (pre-test, post-tDCS, and post-Sham). Results: We observed no significant differences in trunk lean angle, hip and knee frontal plane projection angles, or dynamic valgus index among the three conditions during the five weight-bearing tasks. VAS scores did not differ across the three conditions. Discussion and conclusion: A single session of tDCS did not demonstrate immediate efficacy in enhancing frontal plane kinematics or relieving pain in individuals with PFP. Considering observed positive outcomes in other neurological and orthopedic populations with multi-session tDCS applications, suggesting potential cumulative effects, further research is essential to explore the effects of multi-session tDCS on weight-bearing movement and underlying neurophysiology in individuals with PFP. [ABSTRACT FROM AUTHOR]

Introduction: Bulimia nervosa (BN) is a disorder primarily affecting adolescent females, characterized by episodes of binge eating followed by inappropriate compensatory behaviors aimed at preventing weight gain, including self-induced vomiting and the misuse of diuretics, laxatives, and insulin. The precise etiology of BN remains unknown, with factors such as genetics, biological influences, emotional disturbances, societal pressures, and other challenges contributing to its prevalence. First-line treatment typically includes pharmacotherapy, which has shown moderate effectiveness. Neuroimaging evidence suggests that altered brain activity may contribute to the development of BN, making interventions that directly target the brain extremely valuable. One such intervention is repetitive transcranial magnetic stimulation (rTMS), a non-invasive stimulation technique that has been garnering interest in the medical community for many years. Methods: This review explores the use of rTMS in the treatment of BN. Searches were conducted in the PubMed/Medline, ResearchGate, and Cochrane databases. Results: Twelve relevant studies were identified. Analysis of the results from these studies reveals promising findings, particularly regarding key parameters in the pathophysiology of BN. Several studies assessed the impact of rTMS on binge episodes. While some studies did not find significant reductions, most reported decreases in binge eating and purging behaviors, with some cases showing complete remission. Reductions in symptoms of depression and food cravings were also demonstrated. However, results regarding cognitive improvement were mixed. The discussion focused heavily on potential mechanisms of action, including neuromodulation of brain networks, induction of neuroplasticity, impact on serotonergic dysfunction, anti-inflammatory action, and HPA axis modulation. rTMS was found to be a safe intervention with no serious side effects. Conclusions: rTMS in the treatment of BN appears to be a promising intervention that alleviates some symptoms characteristic of the pathophysiology of this disorder. An additional effect is a significant reduction in depressive symptoms. However, despite these findings, further research is required to confirm its effectiveness and elucidate the mechanisms of action. It is also recommended to further investigate the potential mechanisms of action described in this review. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Objective Methods Results Conclusion This systematic review and meta‐analysis aimed to assess the effectiveness of non‐invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192).We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients.The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta‐analysis was performed.Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = −2.49, [95% confidence interval: −3.34, −1.64]) and ICARS (−5.27 [−7.06, −3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia.Non‐invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high‐quality RCTs are required. [ABSTRACT FROM AUTHOR]

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: - 0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, - 0.63), P=0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. [ABSTRACT FROM AUTHOR]

Abstract Stroke is a major cause of death and disability among adults in China, and an efficient rehabilitation strategy has been an urgent demand for post-stroke rehabilitation. The non-invasive brain stimulation (NBS) can modulate the excitability of the cerebral cortex and provide after-effects apart from immediate effects to regain extremity motor functions, whereas robotic therapy provides high-intensity and long-duration repetitive movements to stimulate the cerebral cortex backward. The combined strategy of the two techniques is widely regarded as a promising application for stroke patients with dyskinesia. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) are important methods of NBS. Their recovery principles, stimulation parameters, and clinical applications have been summarized. The combined treatments of rTMS/tDCS and robotic therapy are analyzed and discussed to overcome the application barriers of the two techniques. The future development trend and the key technical problems are expounded for the clinical applications.

Abstract Frontal and parietal brain regions are involved in attentional control and prospective memory. It is debated, however, whether increased or decreased activity in those regions is beneficial for older adults’ task performance. We therefore aimed to systematically modulate activity in those regions using high-definition transcranial direct current stimulation. We included n = 106 healthy adults (60–75 years old, 58% female) in a randomized, double-blind, and sham-controlled study. We evaluated task performance twice in the laboratory and at home and additionally assessed heart rates. Participants received cathodal, anodal, or sham stimulation of the left or right inferior frontal lobe, or the right superior parietal lobe (1 mA for 20 min). Performance improved at visit two in laboratory tasks but declined in at-home tasks. Stimulation did not modulate performance change in laboratory tasks but prevented decline in at home-tasks. Heart rates increased at visit two but only when right inferior frontal lobe activity was inhibited. Repeating a task seems more beneficial than stimulation for laboratory tasks. This might be different for at-home tasks. Inhibiting right frontal brain function increases heart rates, possibly due to a modulation of the frontal-vagal brain-heart axis.

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer’s disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease. We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

As cognitive neuroscience enters the era of technology application, military psychological training has evolved from traditional behavioral training to cognitive neural training based on neuroimaging, artificial intelligence, virtual reality, and other technologies. Cognitive neural training includes both invasive and non-invasive types, which can be used not only as an adjunct treatment for military occupation-related neuropsychiatric disorders, but also as preventive training that targets the brain to enhance cognitive ablity, regulate emotion, and shape behavior. In this article, we focused on non-invasive cognitive neural training, mainly sorting out the advanced literature concerning non-invasive brain stimulation represented by repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and low-intensity focused ultrasound, as well as neurofeedback mediated by electroencephalography, functional magnetic resonance imaging, and functional near-infrared spectroscopy. We prospected the development trend of intelligent, personalized, multimodal, sensory and wearable neural training, and brought forward and discussed the problems that need our attention in the research and application of cognitive neural training in our army.

Abstract Background Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI. Methods This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane’s risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3. Results We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group. Conclusions Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.

Abstract The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer’s Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials.

• Effects of transcranial static magnetic stimulation (tSMS) are state-dependent. • tSMS increases cortical excitability if applied on an inhibited M1. • Aftereffects of tSMS originate at synaptic level. Aftereffects of non-invasive brain stimulation techniques may be brain state-dependent. Either continuous theta-burst stimulation (cTBS) as transcranial static magnetic field stimulation (tSMS) reduce cortical excitability. Our objective was to explore the aftereffects of tSMS on a M1 previously stimulated with cTBS. The interaction effect of two inhibitory protocols on cortical excitability was tested on healthy volunteers (n = 20), in two different sessions. A first application cTBS was followed by real-tSMS in one session, or sham-tSMS in the other session. When intracortical inhibition was tested with paired-pulse transcranial magnetic stimulation, LICI (ie., long intracortical inhibition) increased, although the unconditioned motor-evoked potential (MEP) remained stable. These effects were observed in the whole sample of participants regardless of the type of static magnetic field stimulation (real or sham) applied after cTBS. Subsequently, we defined a group of good-responders to cTBS (n = 9) on whom the unconditioned MEP amplitude reduced after cTBS and found that application of real-tSMS (subsequent to cTBS) increased the unconditioned MEP. This MEP increase was not found when sham-tSMS followed cTBS. The interaction of tSMS with cTBS seems not to take place at inhibitory cortical interneurons tested by LICI, since LICI was not differently affected after real and sham tSMS. Our results indicate the existence of a process of homeostatic plasticity when tSMS is applied after cTBS. This work suggests that tSMS aftereffects arise at the synaptic level and supports further investigation into tSMS as a useful tool to restore pathological conditions with altered cortical excitability. [ABSTRACT FROM AUTHOR]

This document is a list of references for scientific studies on the use of non-invasive brain stimulation techniques, such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS), in the treatment of cognitive impairment and neurological disorders. The studies cover various topics related to memory function, cognitive performance, and brain connectivity in individuals with conditions like mild cognitive impairment and Alzheimer's disease. The document also includes meta-analyses and systematic reviews that summarize the findings of multiple studies in these areas. Library patrons can use this document to explore further research on the topic. [Extracted from the article]

Purpose: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. Materials and methods: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. Results: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. Conclusions: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment. IMPLICATIONS FOR REHABILITATION: A comprehensive review of non-invasive brain stimulation (NIBS) post-stroke aphasia literature, including all study designs, was required. Review of this literature revealed that anodal transcranial direct current stimulation is the mostly commonly used type of NIBS in aphasia treatment research. Systemic challenges across the field hinder prospective translation of NIBS into aphasia practice. Aphasia rehabilitation professionals should note that further research is required before NIBS is suitable for translation into clinical practice. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: Transcranial direct current stimulation (tDCS) can enhance muscle function in healthy individuals. However, it is unknown if tDCS associated with pelvic floor muscle training (PFMT) can improve pelvic floor muscle function (PFMF) in healthy women. The aim of this study was to investigate the acute effect of a single session of tDCS in PFMF compared with sham-tDCS in healthy women. Methods: A double-blind, cross-over, randomized clinical trial was conducted with healthy, nulliparous and sexually active women. PFMF was assessed by bidigital palpation (PERFECT scale) and intravaginal pressure by a manometer (Peritron™). Participants randomly underwent two tDCS sessions (active and sham) 7 days apart. The electrode was positioned equal for both protocols, the anode electrode in the supplementary motor area (M1) and the cathode electrode in the right supraorbital frontal cortex (Fp2). The current was applied for 20 min at 2 mA in active stimulation and for 30 s in sham-tDCS. The tDCS applications were associated with verbal instructions to PFMT in a seated position. After each tDCS session PFMF was reevaluated. Results: Twenty young healthy women (aged 23.4 ± 1.7 years; body mass index 21.7 ± 2.2 kg/m2) were included. No difference was observed in power, endurance, and intravaginal pressure of PFMF (p > 0.05). The number of sustained contractions improved from 3.0 (2.0–3.5) to 4.0 (3.0–5.0) after active-tDCS (p = 0.0004) and was superior to sham-tDCS (p = 0.01). Conclusion: The number of sustained contractions of PFM improved immediately after a single active-tDCS session, with a difference compared with the post-intervention result of sham-tDCS in healthy young women. [ABSTRACT FROM AUTHOR]

Patients with substance use disorders (SUDs) often suffer from cognitive dysfunction (CD), affecting their quality of life and daily functioning. Current treatments, including pharmacotherapy and psychotherapy, have limited efficacy and notable side effects. Transcranial direct current stimulation (tDCS), a non-invasive technique that modulates cortical activity, shows promise in improving cognitive function with minimal side effects and low cost, and could potentially serve as a valuable adjunct to existing therapies. This systematic review aims to evaluate the literature on the effectiveness of tDCS for CD in SUD patients to inform clinical practice and future research. Following PRISMA guidelines, the review includes studies that used tDCS for SUD-related CD. The criteria for inclusion encompassed participants aged 18 and older with a diagnosis of SUD, the use of tDCS (either conventional or high-definition), control groups receiving sham stimulation or no intervention, and cognitive outcome measures for substance-related cognitive function using validated tools. Databases searched were Ovid MEDLINE, PubMed, Web of Science, Embase, Scopus, and PsycINFO, with specific keywords. Twenty-two studies met the criteria, suggesting tDCS can improve cognitive functions in SUD patients, though results varied. Effectiveness may depend on the brain area targeted, stimulation parameters, task requirements, and individual differences. tDCS shows potential in treating SUD-related CD, but further research is needed to optimize stimulation protocols and address study variability. Future studies should use functional magnetic resonance imaging to explore the brain mechanisms by which tDCS improves cognitive function in SUDs and focus on larger, long-term trials to confirm efficacy and refine tDCS treatment parameters. [ABSTRACT FROM AUTHOR]

Non-invasive brain stimulation techniques allow targeted modulation of brain regions and have emerged as a promising tool for vision rehabilitation. This review presents an overview of studies that have examined the use of non-invasive brain stimulation techniques for improving vision and visual functions. A description of the proposed neural mechanisms that underpin non-invasive brain stimulation effects is also provided. The clinical implications of non-invasive brain stimulation in vision rehabilitation are examined, including their safety, effectiveness, and potential applications in specific conditions such as amblyopia, post-stroke hemianopia, and central vision loss associated with age-related macular degeneration. Additionally, the future directions of research in this field are considered, including the need for larger and more rigorous clinical trials to validate the efficacy of these techniques. Overall, this review highlights the potential for brain stimulation techniques as a promising avenue for improving visual function in individuals with impaired vision and underscores the importance of continued research in this field. [ABSTRACT FROM AUTHOR]

Upper limb weakness following stroke poses a significant global psychosocial and economic burden. Non-invasive brain stimulation (NIBS) is a potential adjunctive treatment in rehabilitation. However, traditional approaches to rebalance interhemispheric inhibition may not be effective for all patients. The supportive role of the contralesional hemisphere in recovery of upper limb motor function has been supported by animal and clinical studies, particularly for those with severe strokes. This review aims to provide an overview of the facilitation role of the contralesional hemisphere for post-stroke motor recovery. While more studies are required to predict responses and inform the choice of NIBS approach, contralesional facilitation may offer new hope for patients in whom traditional rehabilitation and NIBS approaches have failed. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated the potential of non-invasive brain stimulation (NIBS) techniques as a viable treatment option for cerebellar ataxia. However, there is a notable dearth of research investigating the efficacy of NIBS specifically for hereditary ataxia (HA), a distinct subgroup within the broader category of cerebellar ataxia. This study aims to conduct a comprehensive systematic review and meta-analysis in order to assess the efficacy of various NIBS methods for the treatment of HA. A thorough review of the literature was conducted, encompassing both English and Chinese articles, across eight electrical databases. The focus was on original articles investigating the therapeutic effectiveness of non-invasive brain stimulation for hereditary ataxia, with a publication date prior to March 2023. Subsequently, a meta-analysis was performed specifically on randomized controlled trials (RCTs) that fulfilled the eligibility criteria, taking into account the various modalities of non-invasive brain stimulation. A meta-analysis was conducted, comprising five RCTs, which utilized the Scale for the Assessment and Rating of Ataxia (SARA) as the outcome measure to evaluate the effects of transcranial magnetic stimulation (TMS). The findings revealed a statistically significant mean decrease of 1.77 in the total SARA score following repetitive TMS (rTMS) (p=0.006). Subgroup analysis based on frequency demonstrated a mean decrease of 1.61 in the total SARA score after high-frequency rTMS (p=0.05), while no improvement effects were observed after low-frequency rTMS (p=0.48). Another meta-analysis was performed on three studies, utilizing ICARS scores, to assess the impact of rTMS. The results indicated that there were no statistically significant differences in pooled ICARS scores between the rTMS group and the sham group (MD=0.51, 95%CI: -5.38 to 6.39; p=0.87). These findings align with the pooled results of two studies that evaluated alterations in post-intervention BBS scores (MD=0.74, 95%CI: -5.48 to 6.95; p=0.82). Despite the limited number of studies available, this systematic review and meta-analysis have revealed promising potential benefits of rTMS for hereditary ataxia. However, it is strongly recommended that further high-quality investigations be conducted in this area. Furthermore, the significance of standardized protocols for NIBS in future studies was also emphasized. [ABSTRACT FROM AUTHOR]

Both the primary motor cortex (M1) and the cerebellum are crucial for postural stability and deemed as potential targets for non‐invasive brain stimulation (NIBS) to enhance balance performance. However, the optimal target remains unknown. The purpose of this study was to compare the role of M1 and the cerebellum in modulating balance performance in young healthy adults using facilitatory 5 Hz repetitive transcranial magnetic stimulation (rTMS). Twenty‐one healthy young adults (mean age = 27.95 ± 1.15 years) received a single session of 5 Hz rTMS on M1 and the cerebellum in a cross‐over order with a 7‐day washout period between the two sessions. Three balance assessments were performed on the Biodex Balance system SD: Limits of Stability (LOS), modified Clinical Test of Sensory Interaction on Balance (mCTSIB), and Balance Error Scoring System (BESS). No significant effect of rTMS was found on the LOS. The effect of rTMS on the mCTSIB was mediated by stimulation target, proprioception, and vision (p =.003, ηp2 = 0.37). Cerebellar rTMS improved the mCTSIB sway index under eyes closed‐foam surface condition (p =.02), whereas M1 rTMS did not result in improvement on the mCTSIB. The effect of rTMS on the BESS was mediated by stimulation target, posture, and proprioception (p =.049, ηp2 = 0.14). Cerebellar rTMS enhanced reactive balance performance during most sensory deprived conditions. [ABSTRACT FROM AUTHOR]

Introduction: Transcranial direct current stimulation (tDCS) administers lowintensity direct current electrical stimulation to brain regions via electrodes arranged on the surface of the scalp. The core promise of tDCS is its ability to modulate brain activity and affect performance on diverse cognitive functions (affording causal inferences regarding regional brain activity and behavior), but the optimal methodological parameters for maximizing behavioral effects remain to be elucidated. Here we sought to examine the effects of 10 stimulation and experimental design factors across a series of five cognitive domains: motor performance, visual search, working memory, vigilance, and response inhibition. The objective was to identify a set of optimal parameter settings that consistently and reliably maximized the behavioral effects of tDCS within each cognitive domain. Methods: We surveyed tDCS effects on these various cognitive functions in healthy young adults, ultimately resulting in 721 effects across 106 published reports. Hierarchical Bayesian meta-regression models were fit to characterize how (and to what extent) these design parameters differentially predict the likelihood of positive/negative behavioral outcomes. Results: Consistent with many previous meta-analyses of tDCS effects, extensive variability was observed across tasks and measured outcomes. Consequently, most design parameters did not confer consistent advantages or disadvantages to behavioral effects--a domain-general model suggested an advantage to using within-subjects designs (versus between-subjects) and the tendency for cathodal stimulation (relative to anodal stimulation) to produce reduced behavioral effects, but these associations were scarcely-evident in domainspecific models. Discussion: These findings highlight the urgent need for tDCS studies to more systematically probe the effects of these parameters on behavior to fulfill the promise of identifying causal links between brain function and cognition. [ABSTRACT FROM AUTHOR]

Introduction: The conventional method of placing transcranial direct current stimulation (tDCS) electrodes is just above the target brain area. However, this strategy for electrode placement often fails to improve motor function and modulate cortical excitability. We investigated the effects of optimized electrode placement to induce maximum electrical fields in the leg regions of both M1 and SMA, estimated by electric field simulations in the T1 and T2-weighted MRIbased anatomical models, on motor performance and cortical excitability in healthy individuals. Methods: A total of 36 healthy volunteers participated in this randomized, triple-blind, sham-controlled experiment. They were stratified by sex and were randomly assigned to one of three groups according to the stimulation paradigm, including tDCS with (1) anodal and cathodal electrodes positioned over FCz and POz, respectively, (A-P tDCS), (2) anodal and cathodal electrodes positioned over POz and FCz, respectively, (P-A tDCS), and (3) sham tDCS. The sit-to-stand training following tDCS (2 mA, 10 min) was conducted every 3 or 4 days over 3 weeks (5 sessions total). Results: Compared to sham tDCS, A-P tDCS led to significant increases in the number of sit-to-stands after 3 weeks training, whereas P-A tDCS significantly increased knee flexor peak torques after 3 weeks training, and decreased shortinterval intracortical inhibition (SICI) immediately after the first session of training and maintained it post-training. Discussion: These results suggest that optimized electrode placement of the maximal EF estimated by electric field simulation enhances motor performance and modulates cortical excitability depending on the direction of current flow. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMethodResultsConclusionTo evaluate and rank the effectiveness of specific non-pharmacological treatments (NPTs) in improving the global cognitive function in individuals with Alzheimer’s disease (AD) and to examine the dose-response relationship.We conducted a systematic search in PubMed, MEDLINE, Embase, PsycINFO, CENTRAL, WOS, and CNKI from their inception to 15 February 2023. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models.We included 68 studies involving 5053 participants in this meta-analysis. The treatments with the highest cumulative probabilities for improving global cognitive function were transcranial direct current stimulation (tDCS), followed by physical exercise (PE), and repetitive transcranial magnetic stimulation (rTMS). Additionally, cognitive stimulation (CS), cognitive training CT), multidisciplinary program (MD), and reminiscence treatment (RT) also significantly improve the global cognitive function of people with AD. A non-linear dose-response association was observed for tDCS, PE, rTMS, CS, and CT with global cognitive improvement. Notably, no minimal threshold was identified for the beneficial effects of PE on cognition. The estimated minimal doses for clinically relevant changes in cognition were 33 min per week for tDCS, 330 MET-min per week for PE, and 8000 pulses per week for rTMS.tDCS, PE, and rTMS are the better effective NPTs for enhancing global cognitive function in individuals with AD. Properly dosing these treatments can yield significant clinical benefits. Our findings support the clinical utility of low-dose exercise in improving cognition in people with AD. [ABSTRACT FROM AUTHOR]

Non-pharmacological interventions, including cognitive-behavioral therapy (CBT), non-invasive brain stimulation (NIBS), electroconvulsive therapy (ECT), light therapy (LT), and physical rehabilitation/exercise, have shown promise as effective approaches to treat symptoms of depression and anxiety in individuals with Parkinson's disease (PD). In this narrative literature overview, we discuss the state-of-the-art regarding these treatment options and address future perspectives for clinical practice and research. Non-pharmacological interventions hold promise to treat depression and anxiety in PD. There is meta-analytic evidence for the efficacy of CBT, NIBS, ECT, LT, and exercise on improving depressive symptoms. For the treatment of anxiety symptoms, CBT shows large effects but scientific evidence of other non-pharmacological interventions is limited. Importantly, these treatments are safe interventions with no or mild side-effects. More research is needed to tailor treatment to the individuals' needs and combined interventions may provide synergistic effects.We conclude that non-pharmacological interventions should be considered as alternative or augmentative treatments to pharmacological and neurosurgical approaches for the treatment of depression and anxiety in individuals with PD. [ABSTRACT FROM AUTHOR]

Introduction: Long COVID occurs when numerous symptoms begin 3 weeks after acute infection and last for 12 months or more. High‐definition transcranial direct current stimulation (HD‐tDCS) has been tested in patients with COVID‐19; however, previous studies did not investigate the HD‐tDCS use combined with inspiratory muscle training (IMT) for respiratory sequelae of long COVID. Case presentation: Six individuals (four women and two men) aged between 29 and 71 years and presenting with respiratory sequelae of long COVID were included. They were submitted to an intervention that comprised HD‐tDCS combined with IMT twice a week for 5 weeks. Lung function and respiratory muscle assessments were performed at baseline and after 5 weeks of intervention. Implications on physiotherapy practice: HD‐tDCS may enhance the IMT effects by increasing respiratory muscle strength, efficiency, and lung function of individuals with long COVID. [ABSTRACT FROM AUTHOR]

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson's disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper's first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism. [ABSTRACT FROM AUTHOR]

Introduction: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta‐analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. Methods: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). Results: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high‐frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD‐related symptoms, including depression and anxiety symptoms, and overall PTSD severity. Conclusions: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD‐related symptoms. Trial registration: PROSPERO CRD42023391562. [ABSTRACT FROM AUTHOR]

Individuals suffering from long-COVID can present with "brain fog", which is characterized by a range of cognitive impairments, such as confusion, short-term memory loss, and difficulty concentrating. To date, several potential interventions for brain fog have been considered. Notably, no systematic review has comprehensively discussed the impact of each intervention type on brain fog symptoms. We included studies on adult (aged > 18 years) individuals with proven long- COVID brain-fog symptoms from PubMed, MEDLINE, Central, Scopus, and Embase. A search limit was set for articles published between 01/2020 and 31/12/2023. We excluded studies lacking an objective assessment of brain fog symptoms and patients with preexisting neurological diseases that affected cognition before COVID-19 infection. This review provided relevant information from 17 studies. The rehabilitation studies utilized diverse approaches, leading to a range of outcomes in terms of the effectiveness of the interventions. Six studies described noninvasive brain stimulation, and all showed improvement in cognitive ability. Three studies described hyperbaric oxygen therapy, all of which showed improvements in cognitive assessment tests and brain perfusion. Two studies showed that the use of Palmitoylethanolamide and Luteolin (PEA-LUT) improved cognitive impairment. Noninvasive brain stimulation and hyperbaric oxygen therapy showed promising results in the treatment of brain fog symptoms caused by long-COVID, with improved perfusion and cortical excitability. Furthermore, both rehabilitation strategies and PEA-LUT administration have been associated with improvements in symptoms of brain fog. Future studies should explore combinations of interventions and include longer follow-up periods to assess the long-term effects of these treatments. [ABSTRACT FROM AUTHOR]

Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The last decades have witnessed huge efforts devoted to deciphering the pathological mechanisms underlying Alzheimer's Disease (AD) and to testing new drugs, with the recent FDA approval of two anti-amyloid monoclonal antibodies for AD treatment. Beyond these drug-based experimentations, a number of pre-clinical and clinical trials are exploring the benefits of alternative treatments, such as non-invasive stimulation techniques on AD neuropathology and symptoms. Among the different non-invasive brain stimulation approaches, transcranial alternating current stimulation (tACS) is gaining particular attention due to its ability to externally control gamma oscillations. Here, we outline the current knowledge concerning the clinical efficacy, safety, ease-of-use and cost-effectiveness of tACS on early and advanced AD, applied specifically at 40 Hz frequency, and also summarise pre-clinical results on validated models of AD and ongoing patient-centred trials. [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI. Methods: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3. Results: We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group. Conclusions: Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration. [ABSTRACT FROM AUTHOR]

• A virtual reality action observation and motor imagery (VR-AOMI) task was developed. • Effect of VR-AOMI on neuroplasticity was evaluated in twenty healthy adults. • The foundational basis for an early form of LTP synaptic plasticity was quantified. • VR-AOMI was safe, well tolerated, and increased capacity for neuroplasticity. Neuroplasticity is important for learning, development and recovery from injury. Therapies that can upregulate neuroplasticity are therefore of interest across a range of fields. We developed a novel virtual reality action observation and motor imagery (VR-AOMI) intervention and evaluated whether it could enhance the efficacy of mechanisms of neuroplasticity in the human motor cortex of healthy adults. A secondary question was to explore predictors of the change in neuroplasticity following VR-AOMI. A pre-registered, pilot randomized controlled cross-over trial was performed. Twenty right-handed adults (13 females; mean age: 23.0 ± 4.53 years) completed two experimental conditions in separate sessions; VR-AOMI and control. We used intermittent theta burst stimulation (iTBS) to induce long term potentiation-like plasticity in the motor cortex and recorded motor evoked potentials at multiple timepoints as a measure of corticospinal excitability. The VR-AOMI task did not significantly increase the change in MEP amplitude following iTBS when compared to the control task (Group × Timepoint interaction p = 0.17). However, regression analysis identified the change in iTBS response following VR-AOMI was significantly predicted by the baseline iTBS response in the control task. Specifically, participants that did not exhibit the expected increase in MEP amplitude following iTBS in the control condition appear to have greater excitability following iTBS in the VR-AOMI condition (r = −0.72, p < 0.001). Engaging in VR-AOMI might enhance capacity for neuroplasticity in some people who typically do not respond to iTBS. VR-AOMI may prime the brain for enhanced neuroplasticity in this sub-group. [ABSTRACT FROM AUTHOR]

Background: Transcranial focused ultrasound (TFUS) is an emerging neuromodulation tool for temporarily altering brain activity and probing network functioning. The effects of TFUS on the default mode network (DMN) are unknown. Objective: The study examined the effects of transcranial focused ultrasound (TFUS) on the functional connectivity of the default mode network (DMN), specifically by targeting the posterior cingulate cortex (PCC). Additionally, we investigated the subjective effects of TFUS on mood, mindfulness, and selfrelated processing. Methods: The study employed a randomized, single-blind design involving 30 healthy subjects. Participants were randomly assigned to either the active TFUS group or the sham TFUS group. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were conducted before and after the TFUS application. To measure subjective effects, the Toronto Mindfulness Scale, the Visual Analog Mood Scale, and the Amsterdam Resting State Questionnaire were administered at baseline and 30  min after sonication. The Self Scale and an unstructured interview were also administered 30  min after sonication. Results: The active TFUS group exhibited significant reductions in functional connectivity along the midline of the DMN, while the sham TFUS group showed no changes. The active TFUS group demonstrated increased state mindfulness, reduced Global Vigor, and temporary alterations in the sense of ego, sense of time, and recollection of memories. The sham TFUS group showed an increase in state mindfulness, too, with no other subjective effects. Conclusions: TFUS targeted at the PCC can alter DMN connectivity and cause changes in subjective experience. These findings support the potential of TFUS to serve both as a research tool and as a potential therapeutic intervention. [ABSTRACT FROM AUTHOR]

Introduction: HIV is a severe and incurable disease that has a devastating impact worldwide. It affects the immune system and negatively affects the nervous system, leading to various cognitive and behavioral problems. Scientists are actively exploring different therapeutic approaches to combat these issues. One promising method is transcranial direct current stimulation (tDCS), a non-invasive technique that stimulates the brain. Methods: This review aims to examine how tDCS can help HIV patients. Searches were conducted in the Pubmed/Medline, Research Gate, and Cochrane databases. Results: The literature search resulted in six articles focusing on the effects of tDCS on cognitive and behavioral measures in people with HIV. In some cases, tDCS showed positive improvements in the measures assessed, improving executive functions, depression, attention, reaction time, psychomotor speed, speed of processing, verbal learning and memory, and cognitive functioning. Furthermore, the stimulation was safe with no severe side effects. However, the included studies were of low quality, had small sample sizes, and did not use any relevant biomarkers that would help to understand the mechanisms of action of tDCS in HIV. Conclusions: tDCS may help patients with HIV; however, due to the limited number of studies and the diversity of protocols used, caution should be exercised when recommending this treatment option in clinical settings. More high-quality research, preferably involving neurophysiological and neuroimaging measurements, is necessary to better understand how tDCS works in individuals with HIV. [ABSTRACT FROM AUTHOR]

The neural mechanisms underlying language recovery after a stroke remain controversial. This review aimed to summarize the plasticity and reorganization mechanisms of the language network through neuroimaging studies. Initially, we discussed the involvement of right language homologues, perilesional tissue, and domain-general networks. Subsequently, we summarized the white matter functional mapping and remodeling mechanisms associated with language subskills. Finally, we explored how non-invasive brain stimulation (NIBS) promoted language recovery by inducing neural network plasticity. It was observed that the recruitment of right hemisphere language area homologues played a pivotal role in the early stages of frontal post-stroke aphasia (PSA), particularly in patients with larger lesions. Perilesional plasticity correlated with improved speech performance and prognosis. The domain-general networks could respond to increased "effort" in a task-dependent manner from the top-down when the downstream language network was impaired. Fluency, repetition, comprehension, naming, and reading skills exhibited overlapping and unique dual-pathway functional mapping models. In the acute phase, the structural remodeling of white matter tracts became challenging, with recovery predominantly dependent on cortical activation. Similar to the pattern of cortical activation, during the subacute and chronic phases, improvements in language functions depended, respectively, on the remodeling of right white matter tracts and the restoration of left-lateralized language structural network patterns. Moreover, the midline superior frontal gyrus/dorsal anterior cingulate cortex emerged as a promising target for NIBS. These findings offered theoretical insights for the early personalized treatment of aphasia after stroke. [ABSTRACT FROM AUTHOR]

The dorsomedial prefrontal cortex (dmPFC) plays a crucial role in social cognitive functions, including perspective-taking. Although perspective-taking has been linked to self-control, the mechanism by which the dmPFC might facilitate self-control remains unclear. Using the multimodal neuroimaging dataset from the Human Connectome Project (Study 1, N =978 adults), we established a reliable association between the dmPFC and self-control, as measured by discounting rate—the tendency to prefer smaller, immediate rewards over larger, delayed ones. Experiments (Study 2, N = 36 adults) involving high-definition transcranial direct current stimulation showed that anodal stimulation of the dmPFC reduces the discounting of delayed rewards and decreases the congruency effect in egocentric but not allocentric perspective in the visual perspective-taking tasks. These findings suggest that the dmPFC promotes self-control by inhibiting the egocentric perspective, offering new insights into the neural underpinnings of self-control and perspective-taking, and opening new avenues for interventions targeting disorders characterized by impaired self-regulation.

ObjectiveThis study aimed to systematically assess the clinical efficacy of non-invasive brain stimulation (NIBS) for treating post-stroke sleep disorders (PSSD).MethodsWe conducted thorough literature search across multiple databases, including PubMed, Web of Science, EmBase, Cochrane Library, Scopus, China Biology Medicine (CBM); China National Knowledge Infrastructure (CNKI); Technology Periodical Database (VIP), and Wanfang Database, focusing on RCTs examining NIBS for PSSD. Meta-analyses were performed using RevMan 5.4 and Stata 14.ResultsEighteen articles were reviewed, including 16 on repetitive Transcranial Magnetic Stimulation (rTMS), one on Theta Burst Stimulation (TBS), and two on transcranial Direct Current Stimulation (tDCS). Meta-analysis results indicated that rTMS within NIBS significantly improved the Pittsburgh Sleep Quality Index (PSQI) score (MD = −1.85, 95% CI [−2.99, −0.71], p

BackgroundTemporal interference (TI) stimulation, an innovative non-invasive brain stimulation approach, has the potential to activate neurons in deep brain regions. However, the dynamic mechanisms underlying its neuromodulatory effects are not fully understood. This study aims to investigate the effects of TI stimulation on dynamic functional connectivity (dFC) in the motor cortex.Methods40 healthy adults underwent both TI and tDCS in a double-blind, randomized crossover design, with sessions separated by at least 48 h. The total stimulation intensity of TI is 4 mA, with each channel’s intensity set at 2 mA and a 20 Hz frequency difference (2 kHz and 2.02 kHz). The tDCS stimulation intensity is 2 mA. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected before, during, and after stimulation. dFC was calculated using the left primary motor cortex (M1) as the region of interest (ROI) and analyzed using a sliding time-window method. A two-way repeated measures ANOVA (group × time) was conducted to evaluate the effects of TI and tDCS on changes in dFC.ResultsFor CV of dFC, significant main effects of stimulation type (P = 0.004) and time (P < 0.001) were observed. TI showed lower CV of dFC than tDCS in the left postcentral gyrus (P < 0.001). TI-T2 displayed lower CV of dFC than TI-T1 in the left precentral gyrus (P < 0.001). For mean dFC, a significant main effect of time was found (P < 0.001). TI–T2 showed higher mean dFC than tDCS-T2 in the left postcentral gyrus (P = 0.018). Within-group comparisons revealed significant differences between time points in both TI and tDCS groups, primarily in the left precentral and postcentral gyri (all P < 0.001). Results were consistent across different window sizes.Conclusion20 Hz TI stimulation altered dFC in the primary motor cortex, leading to a significant decreasing variability and increasing mean connectivity strength in dFC. This outcome indicates that the 20 Hz TI frequency interacted with the motor cortex’s natural resonance.

Neurodevelopmental disorders such as attention deficit and/or hyperactivity disorder (ADHD) and schizophrenia are characterized by core impairment in executive functions (EF). Despite the development of various behavioral interventions to enhance EF, the evidence is still scarce. Alternatively, non-invasive brain stimulation tools such as transcranial alternating current stimulation (tACS) has emerged as a potential strategy to alleviate cognitive deficits. Previous studies have demonstrated the safety, feasibility, and efficacy of one single tACS session in different clinical populations. However, the effects of tACS appear limited and need to be sustained to be considered an effective cognitive neurorehabilitation tool. Recent studies have used home-based, repeated tACS sessions in individuals with neurodegenerative diseases. To our knowledge, the safety and feasibility of such an intensive protocol remains to be tested in a younger population with neurodevelopmental disorders. Using a randomized double-blind sham-controlled design, we administered home-based, repeated tACS sessions to seven individuals aged 14–25 with 22q11.2 deletion syndrome (22q11.2DS), which confers an increased risk for neurodevelopmental disorders. We aimed to assess the safety, tolerability, and feasibility of tACS. Findings from this ongoing clinical trial revealed a favorable safety profile, with frequent yet transient and mainly mild adverse effects. The intervention proved to be feasible, shown by very high adherence rates and positive user experiences. Future studies should therefore investigate whether prolonged exposure to tACS can lead to long-lasting cognitive outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT05664412.