Search Results (41)

Transcranial electrical stimulation (tES) has been widely investigated for cognitive enhancement and neurorehabilitation; however, its cognitive effects remain highly variable across studies and individuals. Increasing evidence suggests that this variability may be explained by state-dependent and history-dependent plasticity mechanisms rather than stimulation parameters alone. This systematic review aimed to synthesize experimental human studies investigating how stimulation protocols interact with brain state, baseline performance, and prior stimulation history to influence cognitive outcomes. Following PRISMA 2020 guidelines, systematic searches were conducted in PubMed, Scopus, and Web of Science, resulting in 27 eligible experimental studies published between 2008 and 2024. Across cognitive domains such as working memory, declarative memory, perceptual learning, inhibitory control, and creativity, stimulation effects were consistently modulated by baseline performance, task engagement, emotional or physiological state, stimulation timing, and prior stimulation exposure. These findings suggest that transcranial electrical stimulation may be better conceptualized as a state-dependent modulator of neural plasticity rather than a direct cognitive enhancement technique. Overall, the review indicates that protocol-dependent factors such as timing, priming, baseline state, and stimulation history play a critical role in shaping cognitive outcomes. Future research should therefore prioritize state-dependent, task-coupled, and individualized stimulation protocols to improve reproducibility and to better understand variability in cognitive and clinical outcomes. Full article

Background/Objectives: Mild cognitive impairment (MCI) is common in Parkinson’s disease (PD) and significantly impacts quality of life. Non-invasive brain stimulation (NIBS) techniques have emerged as potential therapeutic interventions. This systematic review analyzes the current evidence regarding the efficacy of Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES) on cognitive domains in patients with PD-MCI. Methods: A systematic search was conducted across the PubMed, Scopus, Web of Science, and Medline Ultimate databases up to 20 November 2025. We included studies investigating the effects of NIBS compared to sham stimulation on neuropsychological outcomes in diagnosed PD-MCI patients. Results: Eight studies involving different stimulation protocols were included. Interventions primarily used TMS or tES targeting the left dorsolateral prefrontal cortex (DLPFC). Episodic memory and global cognition were the most responsive domains, assessed with specific neuropsychological scales. Findings for executive functions and attention were heterogeneous, while visuospatial abilities generally showed limited immediate response. Conclusions: NIBS represents a promising but low-certainty-evidence adjunctive therapy for PD-MCI, with improvements found in memory and global cognition. Future research should prioritize larger sample sizes, combined interventions (NIBS plus cognitive rehabilitation), and extended follow-ups to evaluate long-term neuroplasticity. Full article

Chronic pain is a pervasive and debilitating condition that affects millions of individuals worldwide. Unlike acute pain, which serves a protective physiological role, chronic pain persists beyond routine tissue healing and often arises without a discernible peripheral cause. Accumulating evidence indicates that chronic pain is not merely a symptom but a disorder of the central nervous system, underpinned by interacting molecular, neurochemical, and network-level alterations. Molecular neuroimaging using PET and MR spectroscopy has revealed dysregulated excitatory–inhibitory balance (glutamate/GABA), altered monoaminergic and opioidergic signaling, and neuroimmune activation (e.g., TSPO-indexed glial activation) in key pain-related regions such as the insula, anterior cingulate cortex, thalamus, and prefrontal cortex. Converging multimodal imaging—including functional MRI, diffusion MRI, and EEG/MEG—demonstrates aberrant activity and connectivity across the default mode, salience, and sensorimotor networks, alongside structural remodeling in cortical and subcortical circuits. Parallel advances in neuromodulation, including transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), deep brain stimulation (DBS), and emerging biomarker-guided closed-loop approaches, provide tools to perturb these maladaptive circuits and to test mechanistic hypotheses in vivo. This review integrates neuroimaging findings with molecular and systems-level mechanistic insights into chronic pain and its modulation, highlighting how imaging markers can link biochemical signatures to neural dynamics and guide precision pain management and individualized therapeutic strategies. Full article

Background/Objectives: Transcranial electrical stimulation (tES) shows potential for enhancing attention and learning, yet its effects in applied contexts remain underexplored. This study investigated whether transcranial direct current stimulation (tDCS) either alone or in combination with high-frequency transcranial random noise stimulation (hf-tRNS) over the right inferior frontal gyrus (rIFG) could enhance performance in a visual search task requiring target identification and change detection, compared with a low-current control condition. Methods: Sixty-four participants were randomly assigned to receive tDCS alone (2.0 mA), tDCS with hf-tRNS (1.8 mA DC offset combined with 100–500 Hz noise at ±0.18 mA), or low-current control stimulation during training. The task involved identifying vehicles and detecting changes between image presentations. Performance accuracy and EEG oscillatory power were assessed at baseline and post-stimulation. Results: ANCOVA revealed significant effects of stimulation on target identification accuracy (F(2,60) = 3.27, p = 0.045, ηp² = 0.098), with tDCS showing greater improvement than the low-current control condition (p = 0.017). No significant effects were found for change detection for any stimulation condition, or for either the target or change detection for hf-tRNS. Baseline performance moderated stimulation effects: low performers receiving tDCS showed the greatest improvements (F(2,26) = 3.80, p = 0.036, ηp² = 0.226), surpassing even high-baseline performers post-training. EEG analyses revealed that participants who showed greater decreases in frontal theta power demonstrated larger improvements in accuracy with tDCS alone (r = −0.634, p = 0.005) but not with hf-tRNS or the control. Conclusions: tDCS over rIFG selectively enhanced target identification accuracy in a complex visual search, particularly benefiting individuals with lower-baseline performance. These findings suggest tDCS may facilitate training in lower-performing novice populations. Full article

Background and Objectives: Non-pharmaceutical interventions such as cognitive training, transcranial electrical stimulation (tES), and repetitive transcranial magnetic stimulation (rTMS) have shown promise in improving cognitive outcomes in Alzheimer’s disease (AD) and dementia. However, the long-term effects of repeated non-invasive interventions remain unknown. This study investigated whether repeated non-invasive interventions administered over a span of 1 to 3 years were associated with slower cognitive decline compared to typical AD progression, and whether longer no-treatment intervals between treatments predicted greater post-treatment decline. Materials and Methods: Seventy-three participants living with dementia or AD received 2 to 9 blocks of non-invasive treatments (including tES, rTMS, cognitive training). Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores were collected longitudinally up to 3 years (36 months), across multiple intervention and assessment sessions. A mixed-effects model was used to estimate the rate of cognitive decline, adjusting for baseline age, sex, and baseline cognition (MoCA) with participants being the random effect. The observed rate of change was compared to a meta-analysis estimate of AD progression. Additionally, a linear mixed-effects model using robust sandwich estimation of standard errors was employed to assess whether the no-treatment interval was associated with changes in ADAS-Cog scores. Results: Participants showed a significantly slower rate of cognitive decline than expected from the AD reference rate (p < 0.001), with many demonstrating stabilized ADAS-Cog scores during their respective treatment periods, ranging from 1 to 3 years. Medication analyses revealed no significant effect of AD medications, antidepressants, antihypertensives, or cholesterol-lowering agents on cognitive outcomes. Furthermore, longer no-treatment intervals were significantly associated with greater post-treatment decline (p < 0.001). Conclusions: Repeated non-invasive treatments seem to slow the rate of cognitive decline in individuals living with dementia when administered over a prolonged period. This study provides evidence supporting the feasibility and effects of personalized long-term non-invasive treatment strategies for dementia. Full article

Objective: The aim of this study was to examine how transcranial electrical stimulation (tES) modulates intermuscular coherence (IMC) in sprinters and develop an interpretable neural network model for performance prediction. Methods: Thirty elite sprinters completed a randomized crossover trial involving three tES conditions: motor cortex stimulation (C1/C2), prefrontal stimulation (F3), and sham. Sprint performance metrics (0–100 m phase analysis) and lower-limb sEMG signals were collected. A Kolmogorov–Arnold Network (KAN) was trained to decode neuromuscular coordination–sprint performance relationships using IMC and time–frequency sEMG features. Results: Motor cortex tDCS increased 30–60 m sprint velocity by 2.2% versus sham (p < 0.05, η² = 0.25). γ-band IMC in key muscle pairs (rectus femoris–biceps femoris, tibialis anterior–gastrocnemius) significantly heightened under motor cortex stimulation (F > 4.2, p < 0.03). The KAN model achieved high predictive accuracy (R² = 0.83) through cross-validation, with derived symbolic equations mapping neuromuscular features to performance. Conclusions: Targeted tDCS enhances neuromuscular coordination and sprint velocity, while KAN provides a transparent framework for performance modeling in elite sports. Full article

Objectives: This review seeks to evaluate the effectiveness of electrical stimulation (ES) in improving upper limb function in children and young people (CYP) with hemiplegic cerebral palsy (HCP). Methods: A systematic literature search from inception until May 2025 was conducted. Various study designs comparing the effect of different ES techniques such as functional electrical stimulation (FES), transcutaneous electrical nerve stimulation (TENS), neuromuscular electrical stimulation (NMES), transcutaneous spinal cord stimulation (TSCS), and transcranial direct current stimulation (tDCS) on upper limb function in CYP with HCP were included. Results: Eighteen studies were selected for review and quality assessment, comprising twelve randomised controlled trials (RCTs) and six non-RCTs. FES was shown to improve upper limb function, though more rigorous and controlled research is needed. Both TENS and NMES demonstrate potential to improve upper limb function, particularly when combined with other interventions. The analysis suggests that variability in reporting tDCS outcomes hinders assessment of its potential benefits for improving upper limb function. Conclusions: Current research suggests ES may support upper limb rehabilitation in CYP with HCP, though the overall evidence remains limited. Most studies are small, underpowered, and lack long-term follow-up, limiting confident conclusions. ES should therefore be applied cautiously and only as part of a comprehensive rehabilitation plan. Full article

The prevalence and the burden of neurodegenerative diseases is projected to increase in the future, but therapeutic options remain limited, relatively invasive, and not readily accessible. In this context, non-invasive brain stimulation (NIBS) techniques, mainly transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (tES), are emerging as safe and reliable instruments to enhance cognitive performance in asymptomatic individuals and patients with cognitive decline. Nevertheless, these techniques face some limitations that delay their deployment in clinical practice. Here, we describe the current status in the development of these technologies for the treatment of neurodegenerative diseases, and we present a novel promising approach for focally and non-invasively target deep brain regions. In light of these technological advances, we then propose a stepwise research roadmap to achieve an effective clinical translation of these techniques. Firstly, the constitution of open-access multimodal databases will allow to inform future interventions and design a new generation of clinical trials. Secondly, research efforts targeting symptomatic patients will need to assess the impact of NIBS techniques in different forms of dementias and probe their efficacy as disease-modifying therapies. In a future step, randomized clinical trials could focus on highly characterized at-risk populations to probe the impact of NIBS in secondary prevention. Once validated on research grounds, these techniques could enter clinical practice, enhancing cognitive performance in asymptomatic individuals and slowing disease progression in symptomatic patients, ultimately lowering the burden of neurodegenerative diseases. Eventually, NIBS techniques could be integrated into clinical practice within the framework of national Brain Health programs to provide early non-invasive interventions against cognitive decline to patients and individuals at risk. Full article

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons, with a bleak prognosis and few treatment options. Non-invasive brain stimulation (NIBS) techniques, such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), represent emerging approaches aimed at modulating cortical hyperexcitability, a relevant pathogenetic mechanism in ALS. Materials and Methods: A systematic review of the literature was conducted following the PRISMA guidelines, exploring the Scopus and PubMed databases from April to June 2025 with terms related to ALS and NIBS. A total of 18 relevant studies were selected from the initial 708 articles, analysing stimulation protocols, clinical and neurophysiological outcomes, and associated biomarkers; their validity was assessed using the revised Cochrane risk-of-bias (RoB2) tool. Results: The selected studies were extremely heterogeneous, with NIBS techniques, including magnetic (rTMS, cTBS, tSMS) and electrical (tDCS) stimulation, showing variable effects. Low-frequency protocols (1 Hz rTMS) and cTBS showed a slight slowing of clinical progression, while prolonged home stimulation with tDCS and tSMS showed more significant improvements in terms of efficacy, tolerability, and adherence. The main limitations concern the heterogeneity of patients and protocols and the lack of standardised biomarkers, which is why the analysis remained at a descriptive level. The use of telemonitoring and caregiver training are essential to ensure safety and accessibility. Conclusions: NIBS represents a promising therapeutic approach for ALS, but further multicentre, standardised studies with prolonged follow-up are needed. Future strategies should include customisation of stimulation, combination with other therapies, and extension of application to pre-symptomatic phases. Full article

This systematic review examines the combined use of electroencephalography (EEG) and transcranial electrical stimulation (tES) in both clinical and healthy populations. The review focuses on EEG’s role in guiding, monitoring, and evaluating tES interventions and assesses the generalizability of EEG responses to different tES protocols. A comprehensive search across Google Scholar, PubMed, Scopus, IEEE Xplore, ScienceDirect, and Web of Science identified 162 relevant studies using the query: “EEG AND (tDCS OR transcranial direct current stimulation OR tACS OR transcranial alternating current stimulation OR tRNS OR transcranial random noise stimulation OR tPCS OR transcranial pulsed current stimulation)”. Quality was assessed using the Quality Assessment Tool for Quantitative Studies (QATQS). Most studies used EEG post tES to assess neuromodulatory effects, with fewer studies using EEG for protocol design or incorporating real-time EEG for adaptive stimulation. Some studies integrated EEG both before and after stimulation, but considerable heterogeneity in tES parameters and EEG metrics limited reproducibility and comparability. Many studies reported non-significant EEG changes despite standardized approaches. Methodological quality was generally low, and the link between EEG changes and clinical outcomes remains unclear. The findings underscore the potential of EEG-informed, personalized tES protocols, though the use of real-time closed-loop systems remains a limited approach in current research. Full article

Electroencephalography (EEG) is a non-invasive biosensing platform with a spatial-frequency content that is of significant relevance for a multitude of aspects in the neurosciences, ranging from optimal spatial sampling of the EEG to the design of spatial filters and source reconstruction. In the past, simplified spherical head models had to be used for this analysis. We propose a method for spatial frequency analysis in EEG for realistically shaped volume conductors, and we exemplify our method with a five-compartment Boundary Element Method (BEM) model of the head. We employ the recently developed technique for spatial harmonic analysis (Sphara), which allows for spatial Fourier analysis on arbitrarily shaped surfaces in space. We first validate and compare Sphara with the established method for spatial Fourier analysis on spherical surfaces, discrete spherical harmonics, using a spherical volume conductor. We provide uncertainty limits for Sphara. We derive relationships between the signal-to-noise ratio (SNR) and the required spatial sampling of the EEG. Our results demonstrate that conventional 10–20 sampling might misestimate EEG power by up to 50%, and even 64 electrodes might misestimate EEG power by up to 15%. Our results also provide insights into the targeting problem of transcranial electric stimulation. Full article

Transcranial electrical stimulation, as a means of neural modulation, is increasingly favored by researchers. The distribution and magnitude of the electric field generated within the brain may directly affect the results of neural modulation. Therefore, it is important to clarify the change trend of the cortical electric field and the determinants of the induced electric field in the endodermis at different ages during the adult life cycle. In this study, we used SimNIBS software to perform MR image segmentation and realistic head model reconstruction on 476 individuals (aged 18 to 88 years old) and calculated the cortical electric field of four electrode montages commonly used in cognitive tasks. We divided all participants into groups by age with a span of 10 years for each group and compared the electric field distribution patterns, electric field intensities, and focalities of the cortexes and regions of interest related to cognitive tasks within groups. The degree of influence of global and local anatomical parameters on the electric field was analyzed using a stepwise regression model. The results showed that, in the cortexes and regions of interest, the variability of electric field distribution patterns was highest in adolescents (<20 years old) and elderly individuals (>80 years old). Moreover, throughout the adult lifespan, the electric field induced by transcranial electrical stimulation did not decrease linearly with age but rather presented a U-shaped pattern. In terms of the entire adult life cycle, compared with global anatomical parameters (intracranial brain tissue volume), local anatomical parameters (such as scalp or skull thickness below the electrode) have a greater impact on the amplitude of the intracranial electric field. Our research results indicated that it is necessary to consider the effects caused by different brain tissues when using transcranial electrical stimulation to modulate or treat individuals of different ages. Full article

Parkinson’s Disease (PD) is a progressive neurodegenerative disorder characterized by a range of motor and non-motor symptoms (NMSs) that significantly impact patients’ quality of life. This review aims to synthesize the current literature on the application of brain stimulation techniques, including non-invasive methods such as transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), transcranial focused ultrasound stimulation (tFUS), and transcutaneous vagus nerve stimulation (tVNS), as well as invasive approaches like deep brain stimulation (DBS). We explore the efficacy and safety profiles of these techniques in alleviating both motor impairments, such as bradykinesia and rigidity, and non-motor symptoms, including cognitive decline, depression, and impulse control disorders. Current findings indicate that while non-invasive techniques present a favorable safety profile and are effective for milder symptoms, invasive methods like DBS provide significant relief for severe cases that are unresponsive to other treatments. Future research is needed to optimize stimulation parameters, establish robust clinical protocols, and expand the application of these technologies across various stages of PD. This review underscores the potential of brain stimulation as a vital therapeutic tool in managing PD, paving the way for enhanced treatment strategies and improved patient outcomes. Full article

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. Full article

Transcranial electrical stimulation (tES) is increasingly recognized for its potential to modulate cerebral blood flow (CBF) and evoke cerebrovascular reactivity (CVR), which are crucial in conditions like mild cognitive impairment (MCI) and dementia. This study explores the impact of tES on the neurovascular unit (NVU), employing a physiological modeling approach to simulate the vascular response to electric fields generated by tES. Utilizing the FitzHugh–Nagumo model for neuroelectrical activity, we demonstrate how tES can initiate vascular responses such as vasoconstriction followed by delayed vasodilation in cerebral arterioles, potentially modulated by a combination of local metabolic demands and autonomic regulation (pivotal locus coeruleus). Here, four distinct pathways within the NVU were modeled to reflect the complex interplay between synaptic activity, astrocytic influences, perivascular potassium dynamics, and smooth muscle cell responses. Modal analysis revealed characteristic dynamics of these pathways, suggesting that oscillatory tES may finely tune the vascular tone by modulating the stiffness and elasticity of blood vessel walls, possibly by also impacting endothelial glycocalyx function. The findings underscore the therapeutic potential vis-à-vis blood-brain barrier safety of tES in modulating neurovascular coupling and cognitive function needing the precise modulation of NVU dynamics. This technology review supports the human-in-the-loop integration of tES leveraging digital health technologies for the personalized management of cerebral blood flow, offering new avenues for treating vascular cognitive disorders. Future studies should aim to optimize tES parameters using computational modeling and validate these models in clinical settings, enhancing the understanding of tES in neurovascular health. Full article