Search Results (45)

Disorders of consciousness (DoC), including unresponsive wakefulness syndrome/vegetative state (UWS/VS) and minimally conscious state (MCS), remain a major challenge in clinical neurology. Therapeutic options are limited, and prognosis is often uncertain. Transcutaneous stimulation of the auricular branch of the vagus nerve (taVNS) is a non-invasive neuromodulation technique that has gained increasing interest as a potential strategy to promote recovery of consciousness. This narrative review summarizes the anatomical and functional rationale of taVNS, compares invasive and non-invasive vagus nerve stimulation techniques, reviews the biological mechanisms underlying its effects, discusses established clinical applications, technological innovations, and available clinical trial evidence. Current data suggest that taVNS is safe and well-tolerated, with preliminary evidence of applicability in DoC, particularly in patients with MCS. However, heterogeneity in stimulation protocols and the limited number of large-scale randomized controlled trials highlight the need for further standardized research. Full article

Objective. The main objective of this study was to examine the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on psychological, sleep, and performance outcomes in powerlifters. Previous research has primarily focused on taVNS in clinical or healthy samples and showed improvements in psychological functioning, recovery, and sleep. Evidence for beneficial effects of taVNS in healthy athletes, however, is missing so far. Methods. Over the course of 4 weeks, 10 healthy adult powerlifters self-administered taVNS five times a week for 30 min after strength training or before bedtime, in an uncontrolled, single-arm pilot design without a sham or control condition. Measurements were taken at three time points: before the intervention phase (pre), immediately after the 4-week intervention phase (post) and 1 month after the post-assessment (follow-up). Pre, post, and follow-up measurements included various subjective psychological domains (recovery, stress, perceived stress, affect, memory, attention, anxiety, and well-being), objective sleep domains (nocturnal HRV, sleep score, sleep duration, and subjective sleep quality), and submaximal strength performance outcomes in squat, bench press, and deadlift. The small sample size required non-parametric testing. Additionally, a responder analysis was conducted to explore individual differences in outcome-specific responses. Results. Results showed nominally significant pre-post improvements (uncorrected for multiple comparisons) in positive affect and self-reported attentional difficulties, both revealing large effect sizes; however, given the absence of a control group and the lack of correction for multiple comparisons across multiple outcomes tested, these findings should be interpreted as exploratory and hypothesis-generating rather than confirmatory. The remaining psychological domains and sleep outcomes did not show meaningful changes. Regarding performance, only two of the ten participants provided complete baseline training data, so no reliable conclusions about a beneficial effect of taVNS on strength performance could be drawn. The responder analysis was consistent with the two nominally significant findings but did not reveal a clear overall pattern of taVNS effectiveness. Conclusions. The current study is the first to implement a 4-week taVNS intervention in strength training and demonstrate differences in domain-specific responsiveness to taVNS in athletes for psychological health and self-reported cognitive performance. These findings offer important insights into the feasibility and practical application of taVNS in sports settings. Further studies with larger, sham-controlled samples, a pre-registered primary outcome and a longer intervention period are needed to determine whether these preliminary, hypothesis-generating findings reflect genuine effects of taVNS. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by dysregulated host–microbiota interactions, epithelial barrier dysfunction, and aberrant immune activation. Despite advances in biologic and small-molecule therapies, a substantial proportion of patients exhibit incomplete response, loss of response, or treatment-related adverse effects, underscoring the need for novel adjunctive therapeutic approaches. The vagus nerve exerts a pivotal effects on immune homeostasis through the cholinergic anti-inflammatory pathway, thereby integrating peripheral immune sensing with central autonomic regulation. Within the context of IBD, a diminution in vagal tone has been observed to correlate with persistent mucosal inflammation and immune dysregulation. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique that may activate vagal circuits and modulate neuroimmune signaling without surgical intervention. This review endeavors to critically evaluate the potential efficacy of ta-VNS in the context of IBD, with particular emphasis on its discernible effects on immune, epithelial barrier, microbiota-related, and autonomic biomarkers. Emerging evidence, stemming from preliminary investigations, suggests that ta-VNS may exert an influence on inflammatory cytokine profiles, epithelial tight junction integrity, gut microbial composition, and systemic autonomic balance, warranting further elucidation. In addition, the review discusses differential responses between Crohn’s disease and ulcerative colitis, summarizes current preclinical and clinical evidence, and highlights biomarker-based strategies for evaluating therapeutic response in future randomized controlled trials. Although current evidence remains preliminary and stimulation parameters are not yet standardized, ta-VNS represents a promising adjunctive neuroimmune modulation strategy in IBD. Full article

The global obesity epidemic has become one of the most severe public health challenges of the 21st century, and existing treatment strategies have limitations such as poor long-term adherence, significant side effects, or high invasiveness. Dysregulation of feeding behavior is the core driver of obesity, and its precise regulation depends on the complete transmission of gut–brain axis signals. The nucleus of the solitary tract (NTS), as the first central relay station for visceral afferent signals, is a key hub for the regulation of feeding homeostasis. This article reviews the peripheral signal transduction mechanisms of hunger and satiety, the core afferent pathway of the vagus nerve, and the functional heterogeneity of neuron subpopulations within the NTS, focusing on the anatomical basis, neuroimaging evidence, and preclinical and clinical research progress of transcutaneous auricular vagus nerve stimulation (taVNS) targeting the NTS to exert anti-obesity effects. Accumulating evidence suggests that taVNS may modulate the activity of satiety-promoting neurons and attenuate aberrant hyperactivity of TH⁺ catecholaminergic neurons in obesity via the auricular branch of the vagus nerve–NTS pathway, which may in turn bidirectionally suppress homeostatic and hedonic feeding, reduce energy intake, and ameliorate metabolic dysregulation. Current research still has key gaps such as unstandardized stimulation parameters, lack of large-sample long-term randomized controlled trials, and unclear interaction mechanisms between the NTS and higher brain regions. This article provides a theoretical basis for in-depth understanding of the feeding regulatory network of the NTS and the translational application of taVNS in obesity management. Full article

Inflammatory bowel disease, including ulcerative colitis (UC) and Crohn’s disease (CD), is associated with reduced vagus nerve activity and impaired barrier function. Transcutaneous auricular vagus nerve stimulation (taVNS) shows preventive effects in acute colitis, but its impact on intestinal barrier integrity remains unclear. To assess this, C57BL/6 male mice received taVNS (10 V, 20 Hz, 500 µs, 10 min) prior to colitis induction. UC-like colitis was induced using 5% dextran sulfate sodium (DSS) for 120 h with daily taVNS, while CD-like colitis was induced by intrarectal dinitrobenzene sulfonic acid (DNBS, 4 mg) in 30% ethanol with taVNS during induction and for 48 h. TaVNS reduced colonic proliferation in non-colitic mice in a homeostatic manner, as well as in DNBS-colitic mice, and enhanced differentiation. It decreased enteroendocrine cells in non-colitic conditions but not in DSS-colitic mice, and reduced tuft cells in DSS and DNBS groups. TaVNS increased MUC2 in DSS colitis and decreased TFF3 in DNBS controls. It decreased Lgr5⁺ stem cells in DSS controls but maintained them during DSS colitis, while HOPX⁺ stem cells decreased in non-colitic DSS conditions, and fetal-like stem cells remained unchanged. Disease activity index negatively correlated with chromogranin A. TaVNS prevented increased paracellular permeability in the distal colon of DSS-colitic mice, increased TEER in distal DSS controls and proximal colitic colon, and enhanced ion transport in the proximal colon under non-colitic DSS conditions. Overall, taVNS effects on epithelial composition and barrier function are context- and model-dependent. Full article

Objective: This study aims to investigate the acute effects of transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic nervous system (ANS) regulation and spasticity in children with spastic cerebral palsy (SCP). Methods: This preliminary study includes 20 children aged 2–15 years diagnosed with SCP. Participants undergo a single session of taVNS. Spasticity is assessed using the Modified Ashworth Scale, and autonomic regulation is evaluated through heart rate variability (HRV) parameters measured before and immediately after stimulation. Results: Following taVNS, spasticity scores decrease significantly (Modified Ashworth Scale: pre 2.00 ± 0.64 vs. post 1.60 ± 0.52; p = 0.004). Significant reductions are also observed in mean heart rate (pre 98.60 ± 16.32 bpm vs. post 91.25 ± 20.22 bpm; p = 0.022), LF/HF ratio (pre 2.22 ± 2.22 vs. post 1.12 ± 0.84; p = 0.006), and LF power (p = 0.009). No significant changes are detected in RMSSD, pNN50, or HF power (all p > 0.05). No adverse events are reported. Conclusions: This preliminary study suggests that a single session of taVNS may be associated with acute changes in autonomic regulation and reductions in spasticity in children with SCP. The observed shifts in HRV parameters indicate a modulation of sympathovagal balance. These findings support the feasibility of taVNS as a non-invasive neuromodulatory approach and warrant further large-scale, controlled studies with longer follow-up. Because of the small sample size, the absence of a control or sham group, and the short (1-min) HRV recording window, these results should be regarded as preliminary and hypothesis-generating, and they require confirmation in larger, randomised, sham-controlled studies. Clinical Trial Registration: This study was registered at ClinicalTrials.gov (Identifier: NCT06880887) on 10 March 2025. The study was conducted between January 2025 and March 2025; registration on 10 March 2025 therefore occurred during the enrolment and data-collection period rather than prior to it. This retrospective registration is acknowledged as a limitation. Full article

Background: Both neuromodulation and physical therapy have been shown to mitigate motor and non-motor symptoms of Parkinson’s disease. To date, no studies have examined the integration of transcutaneous auricular vagus nerve stimulation (taVNS) with physical therapy approaches for improving Parkinsonian symptoms. The purpose of this study was to investigate the safety, tolerability, and feasibility of combining taVNS with physical therapy to enhance the therapeutic benefits of exercise as medicine in a clinical setting. Methods: Participants were randomly assigned to receive active or sham bilateral taVNS in combination with PT for 12 visits over 6 weeks. Safety, tolerability, and feasibility outcomes were primary. Secondly, exploratory analyses of changes in cardiovascular and motor function over time were also performed. Results: Overall, taVNS was safe and well-tolerated prior to PT. Cardiovascular analyses suggest that active taVNS may augment HR response to exercise compared to sham. For motor outcomes, both groups showed significant overall improvements; however, no significant between-group differences were found. Conclusions: The preliminary results obtained in this pilot trial confirm that taVNS combined with physical therapy for individuals with PD is safe and feasible. The exploratory cardiovascular and motor findings support the need for larger, adequately powered clinical trials investigating the integration of taVNS into PT and exercise methods for improving PD symptomology. Trial registration: ClinicalTrials.gov NCT05871151. Full article

Three-dimensional (3D) ear morphology is critical for the design of in-the-ear hearing aids, earphones, transcutaneous auricular vagus nerve stimulation (taVNS) electrodes, and auricular reconstruction, yet most existing ear shape models still rely on manually placed landmarks. Here, a fully annotation-free pipeline is presented for constructing a 3D ear atlas and statistical shape model (SSM) of the auricular bowl from 50 surface meshes. Individual ears are iteratively registered to a current atlas using rigid the iterative closest point (ICP) algorithm followed by a bidirectional thin-plate spline (BiTPS) deformation, and dense surface correspondences are established by nearest-neighbour mapping. Registration quality is quantified using mean and maximum nearest-neighbour distance, symmetric Chamfer-$L_2$ distance and coverage. Furthermore, SSM-derived bowl height and width are validated against manual 3D mesh measurements in Geomagic Design X. Across five atlas iterations, the BiTPS pipeline substantially reduces registration errors and increases coverage, and principal component analysis (PCA) derived dimensions show excellent agreement with manual measurements (Pearson $r\ge 0.98$, ICC $\ge 0.98$). The proposed framework yields a stable, anatomically plausible ear atlas and an interpretable low-dimensional SSM without manual landmarks, providing a computational basis for the geometric optimization of ear-related medical and wearable devices. Full article

Background: Long COVID, or post-COVID-19 condition (PCC), affects around 36% of individuals following SARS-CoV-2 infection, manifesting as persistent fatigue, cognitive dysfunction, and dysautonomia among its hallmark features. Affecting an estimated 400 million individuals globally, it imposes an annual economic burden exceeding $1 trillion, yet no pharmacological therapy has demonstrated consistent efficacy in adequately powered randomized controlled trials. Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a candidate intervention targeting the autonomic dysfunction and neuroinflammation responsible for PCC pathophysiology. Methods: We conducted a PRISMA 2020-compliant systematic review (PROSPERO: CRD420261287286) searching PubMed, Scopus, Cochrane, and Web of Science databases from inception to January 2026 for studies evaluating any form of VNS in adults with Long COVID. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, the JADAD scale, and the PEDro scale. Certainty of evidence was evaluated using the GRADE framework. Narrative synthesis followed SWiM guidelines. Results: Five studies (n = 154 participants) (three randomized controlled trials (RCTs) and two single-arm studies) met inclusion criteria. Three of five studies (60%) were rated high overall risk of bias; only two RCTs achieved “some concerns.” The only adequately double-blinded RCT found no significant between-group differences across all outcomes. Paradoxically, in the best-powered RCT (Percin et al.), sham stimulation produced significantly greater fatigue improvement than active taVNS, despite active taVNS producing significant HRV increases consistent with cardiac autonomic modulation. All efficacy outcomes were rated “very low” certainty (GRADE); safety was rated “low” certainty. Conclusions: Currently available evidence supporting the use of taVNS for Long COVID remains limited, and the absence of reliable target engagement markers in the included studies constrains confidence in this approach. Nonetheless, the physiological rationale remains sound, and the favorable safety profile across all included studies supports the feasibility of future investigation. However, given that positive findings were confined to inadequately controlled studies, enthusiasm for further research should be directed first toward mechanistic clarification and rigorous dose-finding work. Large-scale, double-blind, sham-controlled trials incorporating validated markers of vagal engagement are required before taVNS can be firmly recommended for COVID-19 sequelae management. 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: Responders to the September 11, 2001, WTC attacks experience high rates of PTSD, and existing treatments often lead to high dropout and low care use. Objectives: This randomized, double-blind, sham-controlled trial assesses the feasibility and acceptability of transcutaneous auricular vagus nerve stimulation (taVNS) as a potential PTSD treatment for 9/11 responders. Methods: A total of 32 WTC responders aged 18+ with PTSD, recruited via the World Trade Center Health Program, participated; those with current psychosis, unstable medical conditions, or recent trial involvement were excluded. Participants were randomly assigned to taVNS or sham groups and asked to use the device for 15 min daily for 8 weeks, with staff and participants blinded. Primary outcomes included recruitment, adherence, retention, and feedback. Secondary outcomes examined changes in depression (PHQ-9), anxiety (GAD-7), and sleep (PSQI). Data were analyzed with mixed-effects models focusing on PTSD and mental health symptoms. Results: The taVNS group showed modest PTSD improvement, with a 10-point CAPS-5 reduction in 40% of stimulation participants versus 28.5% sham; no significant differences in self-reported symptoms were found. Discussion: Daily taVNS over eight weeks is feasible and acceptable, warranting larger studies to detect differences and identify subgroups with greater benefit. Trial registration: “taVNS to Reduce PTSD Symptoms in WTC Responders” (NCT05212714); registered 9 September 2021. Full article

Transcutaneous electrical nerve stimulation techniques (TENS) are rapidly gaining attention for their potential in various clinical applications. One such technique is transcutaneous auricular vagus nerve stimulation (taVNS), and it involves delivering nerve stimulation through the skin of the external ear. However, taVNS relies on electrodes that must conform to the complex anatomy of the ear while maintaining stable electrical performance. Conventional taVNS electrodes, typically rigid metal or adhesive pads, are uncomfortable, difficult to position, prone to drying, and costly to produce. Here, we present and evaluate two complementary fabrication approaches for soft dry electrodes suitable for taVNS, which are compliant with curved anatomical features and can be operated without gel. The first employs wet spinning of a conductive elastomer into fibers, while the second extends this method to create hollow cylindrical geometries. The resulting spongy polymer composite electrodes exhibit tunable geometry, high conductivity, mechanical resilience under strain and compression, and low material impedance confirmed through bench and human testing, even under dry conditions. These properties are critical for in-ear and broader transcutaneous stimulation applications, highlighting the potential of these fabrication methods for next-generation soft bioelectronic interfaces. Full article

Background: Stroke is a leading cause of long-term disability worldwide. Non-invasive or transcutaneous auricular vagus nerve stimulation (taVNS) shows promise in promoting neuroplasticity and supporting motor recovery. There are currently no validated biomarkers of taVNS. High-density diffuse optical tomography (HD-DOT) is a portable neuroimaging technology that uses near-infrared light to map cortical activity via the quantification of changes in blood oxygenation. The aim of this study was to determine whether HD-DOT could detect motor task-related activity with concurrent taVNS. Methods: Thirty-one healthy participants completed right and left finger tapping tasks with concurrent sham (earlobe) and then active (tragus) taVNS in a within-subject block design. HD-DOT was recorded across the bilateral sensorimotor cortex using 36 sources and 48 detectors (1728 channels). Cortical reconstructions were parcellated and block-averaged task-related oxygenated and deoxygenated haemoglobin changes were compared between sham and active taVNS conditions. Results: In a group-level analysis, appropriate lateralised task-related haemodynamic responses were seen in the contralateral sensorimotor regions, demonstrating the validity of HD-DOT. Between-group comparisons showed no significant change in task-related activation during right finger tapping tasks under active vs. sham taVNS conditions. A non-significant redistribution of task-related activity to the right motor cortex was seen with left finger tapping under active taVNS compared to sham taVNS. Conclusions: Simultaneous recording of neural responses to taVNS during motor activity was feasible and well tolerated. Reliable task-related activation was recordable. Future studies of whole brain HD-DOT in people with stroke will help evaluate its potential as a biomarker in taVNS. Full article

Pain in children and adolescents remains an underestimated and undertreated condition, with long-term physical and psychosocial consequences. Non-invasive neuromodulation has emerged as a promising, low-risk approach for managing acute and chronic pain by modulating central and peripheral neural pathways. This systematic review followed PRISMA 2020 guidelines to evaluate the efficacy, safety, and clinical applicability of non-invasive neuromodulation techniques in pediatric pain. Searches were conducted in PubMed, Embase, Scopus, Web of Science, Cochrane CENTRAL, and ScienceDirect for randomized controlled trials (RCTs) published between 2015 and 2025. Six RCTs met the inclusion criteria, encompassing percutaneous electrical nerve field stimulation (PENFS), transcutaneous auricular vagus nerve stimulation (taVNS), transcutaneous electrical acupoint stimulation (TEAS), and transcutaneous electrical nerve stimulation (TENS). Four trials reported significant reductions in pain intensity alongside improvements in functional outcomes and quality of life, particularly in functional abdominal pain and postoperative contexts. Most studies showed low or moderate risk across domains, with appropriate randomization and blinded assessment. No serious adverse events were reported, confirming an excellent safety profile. These findings support non-invasive neuromodulation as a feasible and well-tolerated adjunct to conventional pediatric pain management. Further high-quality trials are warranted to standardize protocols and explore mechanisms of neuroplasticity in the developing nervous system. PROSPERO (CRD420251170866). Full article

Background: Currently, there is a considerable number of studies addressing vagus nerve stimulation (VNS) for the treatment of different stroke-related outcomes. We aimed to promote a broad view of the outcomes studied and what are the opportune outcomes to be studied involving this therapeutic strategy for the treatment of post-stroke complications. Methods: This is a scoping review that followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two investigators conducted independent searches on PubMed/MEDLINE, Scopus, and Embase till July 2025. Randomized clinical trials and preclinical studies using invasive or non-invasive vagus nerve stimulation conducted with a population diagnosed with stroke were included. Results: Forty-one experimental studies and sixteen clinical trials were included. The outcomes found were neuroprotection; motor, functional, and cognitive rehabilitation; dysphagia; comparison of different stimulation intensities; safety, efficacy, and feasibility of the non-invasive approach; comparison between transcutaneous auricular vagus nerve stimulation (taVNS) and transcutaneous cervical vagus nerve stimulation (tcVNS); and comparison between two models of ischemia (permanent and transient). Preclinical studies mostly investigated molecular elements involved in neuroprotection, neuroinflammation, and cellular apoptosis, while clinical studies evaluating the effectiveness of this technique used for rehabilitation and its comparison or combination with other techniques remain scarce. Conclusions: Most studies investigating the effects of VNS on different post-stroke outcomes are experimental studies. Clinical studies are still scarce and with limited analysis of outcomes. Full article