Search Results (490)

Background: Globally, around 400 million people are estimated to be affected by long COVID, yet treatment options remain scarce. A systematic review published in 2025 indicated that non-invasive brain stimulation may help reduce some long COVID symptoms. If repetitive transcranial magnetic stimulation (rTMS) has therapeutic potential for these patients, then a clear synthesis of the evidence is necessary to determine efficacy and potential for implementation. Methodology: This systematic review and narrative synthesis was conducted in accordance with PRISMA guidelines. The search, completed on the 4th of December 2025, covered four databases and grey literature. Studies were included if they examined long COVID and rTMS. Findings: A meta-analysis was not possible due to insufficient reported data across studies. Instead, a structured narrative synthesis was conducted on four included studies. The structured narrative synthesis of four studies indicates that rTMS is feasible and is associated with reported improvements in fatigue, mood, and cognitive symptoms in individuals with long COVID. However, all included evidence is based on uncontrolled case series and retrospective analyses, meaning no causal conclusions can be drawn and findings should be interpreted as exploratory. Conclusions: Taken together, the evidence remains preliminary and highlights the need for well-designed randomised controlled trials to assess efficacy. Full article

Introduction: Navigated transcranial magnetic stimulation (nTMS) is an advanced, noninvasive method for stimulation-based functional brain mapping. Its main clinical value in neurosurgery lies in preoperative identification of eloquent cortical areas and the integration of functional information into neuronavigation-based surgical planning. State of the Art: This narrative review with a structured literature search summarizes the historical and technical foundations of TMS/nTMS, but primarily focuses on neurosurgical applications, including motor and language mapping, comparison with functional MRI and direct cortical stimulation, safety considerations, and practical limitations. Broader neurological and therapeutic applications are discussed as contextual extensions rather than as a comprehensive disease-specific review. Clinical Implications: Current evidence is strongest for preoperative motor mapping in patients with tumors located in or near the motor–eloquent cortex. Language mapping, neurological diagnostics, and therapeutic repetitive TMS (rTMS) applications remain more heterogeneous and require careful interpretation according to the level of evidence, protocol standardization, and patient selection. Future Directions: Further multicenter studies, standardized mapping protocols, integration with advanced imaging and tractography, and health-system implementation strategies are needed to define the optimal role of nTMS in personalized neurosurgical and neurological care. Full article

Background/Objectives: The growing aging population is susceptible to cognitive and memory impairment, most commonly due to Alzheimer’s disease, with no cures currently available. Noninvasive brain stimulation (NIBS) techniques may serve to improve cognition and delay catastrophic memory loss. Methods: A systematic review of NIBS research on cognitive impairment was carried out using PubMed, with additional backward citation searching. A total of 81 studies using NIBS were included. Conclusions: The reviewed studies show that NIBS holds promise in improving memory deficits in patients with cognitive impairment. While the longevity of benefits from transcranial electrical stimulation appears limited, its short-term effects may provide benefits when used consistently. Transcranial magnetic stimulation appears to provide longer-lasting benefits. Transcranial focused ultrasound stimulation may also provide further benefits through more precise targeting of deeper brain structures compared to other NIBS techniques. Together, these results suggest that NIBS shows promise for the treatment of symptoms related to cognitive and memory impairment, and may help to alleviate some of the growing issues associated with the increasing level of Alzheimer’s disease in an aging population. Full article

Frontotemporal dementia (FTD) is a heterogeneous disorder for which disease-modifying treatments are lacking. Non-invasive brain stimulation (NIBS) has emerged as a potential therapeutic approach to modulate dysfunctional neural networks and support residual plasticity. This systematic review aims to provide an updated overview of current NIBS applications across the main clinical syndromes associated with FTD, namely behavioral variant FTD (bvFTD), semantic variant of primary progressive aphasia (svPPA), and nonfluent variant of PPA (nfvPPA). According to PRISMA guidelines, twenty-seven studies investigating NIBS interventions in major FTD phenotypes met the inclusion criteria, predominantly employing transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS). tDCS, particularly when combined with language therapy, consistently improved several language abilities in PPA, with some evidence of maintenance over time. Benefits were most consistently reported in nfvPPA, whereas effects in svPPA were more limited and domain-specific. rTMS studies showed short-term improvements in language and executive functions, especially following stimulation of left frontal regions. In bvFTD, findings were heterogeneous, with social–cognitive outcomes appearing more sensitive to stimulation, whereas global cognitive measures showed more variable effects. NIBS, particularly tDCS combined with behavioral interventions, shows symptomatic potential in selected FTD phenotypes, but methodological heterogeneity and small samples warrant larger, well-controlled trials. Full article

Neuropsychiatric disorders are characterized by complex etiologies, widespread involvement of brain regions, and pronounced clinical heterogeneity, with core pathological mechanisms closely associated with abnormal activity in deep brain structures and their functional networks. Although current pharmacological therapies and conventional neuromodulation techniques have shown therapeutic benefits in certain conditions, they are generally limited by insufficient stimulation depth or the risks associated with invasive procedures. Temporal interference (TI) electrical stimulation has recently emerged as a non-invasive deep neuromodulation technique that generates low-frequency difference-envelope fields through high-frequency carrier signals, thereby enabling relatively precise modulation of deep brain regions while maintaining favorable safety and tolerability. This technique provides a novel technical pathway for precision intervention in neuropsychiatric disorders. In this review, we summarize the principles and technical characteristics of TI stimulation and highlight its recent applications in mood and stress-related disorders, cognitive impairment and neurodegenerative diseases, movement disorders, addiction, and disorders associated with dysregulated neural excitability. We integrate its potential mechanisms across multiple levels, including neural oscillations, deep–cortical network synchronization, reward and motivational circuits, synaptic plasticity and structural remodeling, excitatory-inhibitory balance, and gene and epigenetic regulation. Current evidence suggests that TI stimulation can modulate electrophysiological activity and may engage molecular and network-level processes relevant to functional improvement, although durable clinical benefits remain to be established. Although clinical translation remains challenged by parameter optimization, interindividual variability, and long-term safety evaluation, advances in computational modeling, multimodal neuroimaging, and closed-loop stimulation strategies are expected to facilitate its development. Overall, TI stimulation represents a promising non-invasive deep neuromodulation approach for mechanistic investigation and precision treatment of neuropsychiatric disorders. Full article

Background/Objectives: Attention-Deficit/Hyperactivity Disorder (ADHD) is associated with working memory deficits linked to frontoparietal alterations. Non-invasive brain stimulation (NIBS) is a potential intervention to modulate neuroplasticity and improve this executive function. In this study, we aimed to evaluate the clinical efficacy of non-invasive brain stimulation techniques (tDCS/rTMS) for strengthening working memory in children and adolescents with ADHD. Methods: This systematic review adhered to the PRISMA 2020 guidelines, with a search of Scopus and Web of Science conducted to identify relevant studies published between 2011 and 2026. Eligibility criteria, defined a priori, included original empirical studies (RCTs and quasi-experimental designs) focusing on pediatric populations (≤18 years) diagnosed with ADHD. Eligible interventions involved tDCS or rTMS with explicit working memory outcomes. Only peer-reviewed articles published in English or Spanish were included. Reviews, case reports, and studies exclusive to adults were excluded. Data on application parameters, durability, and safety were extracted for narrative synthesis. Results: Six studies met the criteria. Both tDCS and rTMS targeting the left dorsolateral prefrontal cortex showed improvements in working memory, particularly in executive components measured using digit span backward and N-back tasks. High-frequency rTMS (10 Hz) with repeated sessions showed more consistent effects, while tDCS showed modest and variable improvements. Evidence regarding long-term effects was limited. Both techniques were well-tolerated, with mild and transient adverse events. Conclusions: NIBS shows promise as a complementary intervention to improve working memory in pediatric ADHD; however, current evidence is limited. Larger, standardized, longitudinal trials are required to confirm its efficacy and clinical utility. Full article

Vagus nerve stimulation (VNS) may improve cognition and promote underlying brain health through various mechanisms including the noradrenaline and cholinergic pathways. Whilst early human studies used invasive devices (iVNS), recent decades have seen the emergence of non-invasive devices that stimulate the vagus nerve transcutaneously (tVNS) via either the cervical branches in the neck (tcVNS) or the auricular branch in the ear (taVNS). With this increase in more accessible devices, tVNS is gaining interest as a novel therapy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This targeted review aims to understand the current evidence in human trials in this specific population. PubMed, Cochrane, EMBASE, MEDLINE, and Google Scholar were searched. Six human interventional studies were found (one iVNS; five taVNS). VNS is well tolerated and study designs demonstrate feasibility within this population for future blinded and appropriately powered long-term studies with participants applying tVNS at home. However, protocols and tVNS settings remain variable. Working memory domains such as verbal fluency and 3D processing show the most promise but global cognitive scores were also sensitive in some cases. The role of biomarkers of tVNS activity and its effect on AD markers and neuroinflammation should be considered in the design of future studies. Full article

Background: We synthesized evidence from randomized clinical trials (RCTs) published between 2019 and 2025 on repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI) and compared different stimulation parameters, cortical targets, and combinations with rehabilitation interventions. Methods: A systematic review according to PRISMA guidelines examined the RCTs applying rTMS in adults with PSCI compared with control or sham groups. The primary outcome was improvement in cognitive function and functional outcomes measured with standardized scales. Results: Fifteen studies, involving a total of 732 patients, were included. The most frequently investigated were high-frequency (≥10 Hz) stimulation protocols of the left dorsolateral prefrontal cortex, with treatment cycles ranging from 2 to 6 weeks. Overall, rTMS was generally safe and well tolerated, with rare and mild adverse events. Several studies reported improvements in cognitive performance following rTMS, although effects were variable across trials and need caution in light of heterogeneity in stimulation protocols, sample sizes, outcome measures, and methodological quality. In most cases, rTMS or intermittent theta burst stimulation combined with structured cognitive training yielded greater cognitive and functional gains than stimulation or rehabilitation alone. This suggests a positive interaction between rTMS and cognitive training, although current evidence does not yet allow definitive conclusions. Conclusions: rTMS appears to be a promising strategy for post-stroke cognitive rehabilitation, particularly for attention and executive functioning. However, heterogeneity in stimulation protocols and outcome measures, along with limited sample sizes and short follow-up, reduces the certainty and comparability of current evidence. The widespread reliance on global screening tools may further underestimate domain-specific effects. Future multicentre trials with standardized protocols and more sensitive cognitive assessments are needed to clarify efficacy and guide further clinical application of rTMS in PSCI. Full article

Background/Objectives: Tobacco use is a leading cause of preventable death worldwide and is linked to major health and economic burden. Many smokers attempt to quit, yet long-term success rates with current medicines and counseling are still modest. Long-term nicotine exposure distorts brain systems involved in reward, craving, and self-control. These changes weaken inhibitory control and strengthen responses to smoking cues, which increases the risk of relapse. Transcranial magnetic stimulation (TMS) is a non-invasive technique that delivers magnetic pulses to specific cortical regions, most commonly the dorsolateral prefrontal cortex, to influence neural activity. This narrative review explored how transcranial magnetic stimulation may aid smoking cessation by acting on neural circuits linked to nicotine dependence. Methods: Five major databases were searched for studies published between 2015 and 2026. After removal of duplicates and screening, a total of 34 studies were included in this narrative synthesis. Randomized controlled trials, clinical studies, and neuroimaging investigations involving adults with nicotine dependence were included. A thematic narrative method was employed to synthesize findings due to the differences in study designs, protocols, and outcome measures. Results: TMS has been shown to attenuate cravings, decrease daily cigarette consumption, and decrease nicotine dependence in various studies. Several trials reported higher abstinence rates with active stimulation compared with sham treatment. Meta-analytic findings indicate stronger effects with 10 Hz stimulation and treatment courses of 20 sessions or more. Neuroimaging studies report changes in functional connectivity within reward, executive control, and salience networks, suggesting partial restoration of disrupted circuits. Treatment response varies according to age, educational level, baseline dependence, and stimulation parameters. Conclusions: These findings support transcranial magnetic stimulation as a promising brain-based approach for smoking cessation, while further well-designed trials with longer follow-up are still needed. Full article

Selectively modulating specific brain-rhythm bands with physical stimuli helps both to reveal neural mechanisms and to provide non-pharmacological treatment avenues for brain disorders. This study proposes and implements a multi-channel transcranial magneto-acoustic stimulation driving system based on amplitude-modulated (AM) sine waves (AM-TMAS) intended to supply a reliable hardware platform for noninvasive, focal low-frequency rhythmic electrical stimulation of deep-brain structures. The driving system implements a 64-channel AM module based on an FPGA plus high-speed DACs. Multi-channel precision is achieved via a unified high-speed clock and a global UPDATE trigger. To overcome the large separation between envelope and carrier frequencies, we developed a high-fidelity AM waveform generation method based on DDS + LUT + envelope multiplication. The algorithm first centers the carrier samples to preserve waveform symmetry, then applies LUT-based envelope coefficients and fixed-point envelope multiplication, enabling high-precision AM outputs with carrier frequencies from 100 kHz to 2 MHz and envelope frequencies from 0.1 Hz to 100 kHz. We tested the system’s rhythmic multi-channel AM output performance across frequencies and also measured magneto-acoustic-coupled rhythmic electrical signals produced by the AM-TMAS driving setup. Any single channel reliably produced high-fidelity AM waveforms with a 500 kHz carrier and 8 Hz/40 Hz envelopes; the measured carrier was 499.998 kHz with excellent frequency stability. Both envelope and carrier frequencies are flexibly tunable. At the nominal 500 kHz carrier, envelope fidelity was further quantified: the extracted envelopes achieved NRMSEs of 1.0795% (8 Hz) and 1.9212% (40 Hz), confirming high-fidelity AM synthesis. Under a 0.3 T static magnetic field, the AM-TMAS driving system generated rhythmic electrical responses in physiological saline that carried the expected 40 Hz envelope. The proposed AM-TMAS driver achieves high accuracy in AM waveform generation and robust multi-channel performance, and—when combined with an external static magnetic field—can produce rhythmically modulated magneto-acoustic electrical stimulation. This platform provides a practical technical tool for brain-function research and the development of rhythm-targeted neuromodulation therapies. Full article

Low-field magnetic stimulation (LFMS) has been proposed as a non-invasive approach for modulating cortical oscillations through electromagnetic coupling. Frequency-aligned enhancement of alpha-band activity is of interest due to its association with cortical inhibitory balance and relaxed wakefulness. This study investigates whether a 10 Hz LFMS applied to the occipital area can induce measurable alpha-band modulation. Electromagnetic simulations were performed to determine magnetic flux distributions within a simplified spherical head model with magnetic susceptibility, which was approximating the brain’s parameters. The 10 Hz stimulation waveform—a positive ramp sawtooth—was analyzed in both time and frequency domains. Electroencephalographic (EEG) recordings were obtained before and after stimulation, and spectral analyses of relevant occipital channels were used to quantify the power redistributions. Simulations indicated localized magnetic field gradients in the occipital region. Post-stimulation EEG recordings showed a redistribution of spectral power toward the alpha-band, representing approximately 50% of total occipital spectral power, with relative increases exceeding 140% across the analyzed channels. These combined modeling and electrophysiological findings provide preliminary proof-of-concept evidence that frequency-aligned LFMS is associated with a redistribution of spectral power toward the alpha-band. Full article

Effective rehabilitation tools are essential for improving language outcomes in chronic aphasia. Speech entrainment is a behavioral treatment that has shown promise in enhancing speech output in nonfluent aphasia, potentially by acting as an external mechanism to synchronize anterior and posterior language regions in the left hemisphere. Transcranial alternating current stimulation has been hypothesized to enhance functional connectivity between brain regions by amplifying endogenous oscillations. This proof-of-concept study explored whether high-definition tACS (HD-tACS) could improve speech fluency in nonfluent aphasia when paired with speech entrainment. In a double-blind, pseudorandomized study, 1 mA of HD-tACS at 7 Hz was applied to anterior and posterior left-hemisphere regions of individuals with nonfluent aphasia (N = 13). Stimulation was applied under three conditions: in-phase, anti-phase, and sham, and paired speech entrainment. Three outcome measures were examined: (1) number of words produced; (2) number of errors, and (3) ‘entrainment’ to the speech entrainment model. Group-level analyses for two of the three outcome measures reveal statistically significant differences between the experimental conditions. In-phase alternating current stimulation yielded more words and better entrainment to the audiovisual model than the sham condition. This study provides promising evidence that HD-tACS could improve speech production in individuals with nonfluent aphasia. These results contribute to growing evidence supporting the therapeutic potential of non-invasive brain stimulation approaches as an adjuvant to traditional behavioral speech-language therapy in stroke survivors. 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

Background: Non-invasive brain stimulation (NIBS) is increasingly used as an adjunctive option in late-life depression (≥60 years), a condition frequently complicated by multimorbidity and incomplete response to standard treatments. Comparative real-world evidence between repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), particularly including functional outcomes, remains limited. Methods: We conducted a retrospective, naturalistic comparative study of 104 depressed inpatients (≥60 years), either unipolar or bipolar, treated with rTMS (n = 48) or tDCS (n = 56) as part of routine care. Depression severity was assessed with the 21-item Hamilton Depression Rating Scale (HDRS21) at baseline, 2 weeks, and 1 month; response was defined as ≥50% HDRS21 score reduction and remission as HDRS21 < 7 at 1 month. Global Assessment of Functioning (GAF) was assessed at admission and discharge (baseline and 1 month). Longitudinal changes were examined using covariate-adjusted mixed-effects models; categorical outcomes were compared using χ² tests. Propensity score matching was applied as an additional approach to reduce confounding due to the observational design. Results: At 1 month, response and remission rates were significantly higher in the rTMS group than in the tDCS group (87.5% vs. 55.4%, p < 0.001; 62.5% vs. 41.1%, p = 0.047, respectively). rTMS showed greater HDRS21 score reductions at 2 weeks and 1 month (Time × Treatment, p < 0.001). GAF scores significantly improved over time in both groups (Time effect, p < 0.001) without between-technique differences (Time × Treatment, p = 0.56), and GAF scores did not differ by response/remission status. Conclusions: In this cohort of inpatients aged ≥ 60 years with depressive episodes, rTMS was associated with greater short-term reductions in HDRS21 scores compared with tDCS, whereas both modalities showed comparable improvements in GAF from admission to discharge. Full article

Human physiology is among the most complex systems in nature, characterized by intricate structural and functional networks and rich temporal dynamics. Electrophysiological signals produced by different tissues/organs reflect physiological activity, and are inherently non-stationary, non-linear, and noisy. This work focuses on fractal analysis, a framework that captures the self-similar and scale-free properties of electrophysiological signals, which is considered to act as an output of complex physiological structures that generate complex processes. Central to this approach is the principle of ‘decomplexification’, whereby aging and disease are associated with a loss of physiological complexity. We discuss key algorithms, particularly Higuchi’s fractal dimension, which is often combined with other nonlinear measures and machine-learning models for real-time analysis of electrophysiological signals. Evidence shows that fractal metrics enable the early detection and monitoring of neurological and psychiatric disorders, outperforming traditional spectral measures. In movement disorders and mood disorders, fractal and nonlinear features show high diagnostic accuracy. Beyond diagnostics, we discuss therapeutic applications, including the prediction of responsiveness to non-invasive brain stimulation. Here, we envisage the evolution of one fractal or nonlinear measure use, to several measures applied, then use it as a feature for machine learning, and then realize that a whole cluster of biomarkers must be used to reflect the state of autonomic profile, which then can be used for ontology-based application profiles that can be machine-actionable. In addition, we discuss the fractal and fractional description of transport processes, which offer innovative improvement for a much more accurate description of physiological reality as a prerequisite for further modeling: for example, this is needed for digital twins to support the clinical translation of fractal analysis for personalized medicine. In essence, if one is trying to mathematically describe or quantify structures or processes in human physiology, fractal and fractional are the supreme and adequate approach to accurately model that reality. Full article