Search Results (57)

Transcutaneous auricular vagus nerve stimulation (taVNS), an emerging noninvasive neuromodulation technique, has shown promise for improving memory. A better understanding of the epigenetic mechanisms underlying the effects of taVNS would inform the molecular outcomes essential for memory and cognition. In this review, we synthesize the current literature on the neurophysiological and biochemical basis of taVNS. Next, we explore how DNA methylation regulators (e.g., DNA methyltransferase 3a) and readers (e.g., methyl-CpG binding protein 2) differentially regulate memory, and how their activity and expression can be regulated by neuronal activity. Finally, we describe the potential involvement of DNA methylation in mediating the memory regulatory effects of taVNS and discuss possible directions for future studies. Full article

This review explores current and emerging neuromodulation techniques targeting the cardiac autonomic nervous system for the treatment and prevention of atrial and ventricular arrhythmias. Arrhythmias remain a significant cause of morbidity and mortality, with the autonomic nervous system playing a crucial role in arrhythmogenesis. Interventions span surgical, pharmacological, and bioelectronic methods. We discuss the range of neuromodulation methods targeting the stellate ganglion, the spinal region, the parasympathetic system, and other promising methods. These include stellate ganglion block, stellate ganglion ablation, cardiac sympathetic denervation, subcutaneous electrical stimulation, thoracic epidural anesthesia, spinal cord stimulation, dorsal root ganglion stimulation, vagus nerve stimulation, baroreflex activation therapy, carotid body ablation, renal denervation, ganglionated plexi ablation, acupuncture, and transcutaneous magnetic stimulation. Both preclinical and clinical studies are presented as evidence for arrhythmia management. Full article

Background: Vagus nerve stimulation (VNS) is a frequently used neuromodulation method in recent years. While the mechanism of improvement in diseases such as epilepsy, dementia, and depression is being studied, its potential effect on vestibular dysfunction is also being investigated. The aim of our study was to investigate the effect of transcutaneous auricular VNS (taVNS) on the vestibular symptoms of unilateral vestibular hypofunction (UVH). Methods: Forty patients diagnosed with UVH were randomly divided into two groups. Group 1 received vestibular rehabilitation. Group 2 received taVNS and vestibular rehabilitation. Both groups received treatment one day a week for eight weeks. Before and after the treatment, balance of the participants was assessed with modified-CTSIB (m-CTSIB), limit of stability (LOS), Tandem and One-Leg Stance (OLS) tests; visual acuity was assessed with dynamic visual acuity (DVA), dizziness severity, and fatigue severity with a visual analog scale (VAS); kinesiophobia was assessed with the Tampa Scale for Kinesiophobia (TSK); depression and anxiety was assessed with the Hospital Anxiety and Depression Scale (HADS); and quality of life was assessed with the Dizziness Handicap Inventory (DHI). Results: At the end of eight weeks, patients in Group 2 showed significantly greater improvement in balance, dizziness, fatigue, kinesiophobia, anxiety, and depression. There was no significant difference in visual acuity and quality of life between the groups. Conclusions: The positive effects of taVNS on vestibular symptoms have been observed. As a new approach, taVNS can be included in the treatment of patients with UVH in addition to vestibular rehabilitation. Full article

Patients with type 2 diabetes mellitus (T2DM) predominantly experience mortality due to cardiovascular diseases (CVD), particularly in low- and middle-income nations. Among these, heart failure (HF) is the most severe cardiovascular complication in terms of prognosis and management. Despite advancements in individualized glycemic control and cardiovascular risk management, including the development of novel glucose- and lipid-lowering agents, the prevalence of HF in T2DM patients remains persistently high. This indicates that factors beyond hyperglycemia significantly contribute to the heightened risk of HF associated with T2DM. This review examines critical factors influencing CVD risk in T2DM, particularly the roles of reduced heart rate variability (HRV), a marker of autonomic dysfunction, and chronic inflammation, both of which play pivotal roles in HF pathogenesis. Recent evidence highlights the potential of vagus nerve activation to modulate these risk factors, underscoring its capacity to reduce T2DM-related cardiovascular complications. Specifically, we discuss the therapeutic promise of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive intervention to enhance vagal tone, decrease systemic inflammation, and improve cardiovascular outcomes in T2DM. By addressing the interplay among HRV, microvascular disease, and inflammation, this review provides a comprehensive perspective on the potential utility of taVNS in managing HF in T2DM. Full article

Cerebrovascular accident (CVA) or stroke is a devastating neurological condition with dismal prognosis associated with recurrent episodes that further damage the neuronal networks, thus disabling neuronal plasticity. Vagus nerve stimulation (VNS) has been used in clinical practice to treat epilepsy for several decades and is well accepted as a safe procedure devoid of serious adverse events. Bailey and Bremer demonstrated that VNS has the capabilities to stimulate neuronal pathways that enhance the recovery of damaged cerebral function. Further studies have strengthened these observations, while technology has improved the tolerability of implants, resulting in VNS applications for epilepsy. Several animal models on neural plasticity have improved our understanding of VNS and its ability to provide neuromodulation to improve recovery in stroke patients. The closed-loop stimulation of the vagus nerve with individualized stimulation parameters combined with physical therapy appears to be an attractive option today. VNS is also being tested as a noninvasive trans-cutaneous modality to further improve patient acceptance and tolerability. However, the implantation of VNS is yielding desirable outcomes and appears to be a more reliable treatment for stroke rehabilitation in clinical trials. Full article

Background/Objective: Heart rate variability (HRV) is a key biomarker of autonomic function, linked to morbidity and mortality across various diseases. Transcutaneous auricular vagus nerve stimulation (taVNS) shows therapeutic promise, but its effects on HRV and the influence of specific stimulation parameters remain unclear. This study investigated whether the acute effects of taVNS on HRV depend on combinations of stimulation frequency and pulse width. Methods: Seventy-eight healthy adults participated in seven randomized sessions, each testing one of six active taVNS protocols or an inactive sham condition applied to the cymba conchae of the left ear. The active protocols varied by frequency (10 Hz or 25 Hz) and pulse width (100 µs, 250 µs, or 500 µs). The sessions included 15 min of baseline, 15 min of taVNS or sham condition, and 10 min of recovery. HRV was calculated using the standard deviation of NN intervals (SDNN) and the root mean square of successive differences (RMSSD) from continuous ECG recordings. Results: The 10 Hz/250 µs, 10 Hz/500 µs, and 25 Hz/100 µs protocols significantly increased SDNN time series compared to the sham condition. Exploratory analysis revealed SDNN increases during the second 5 min of stimulation with the 10 Hz/500 µs protocol and during the first 5 min of recovery with the 10 Hz/250 µs and 25 Hz/100 µs protocols. No significant changes in the RMSSD were found for any protocol. Conclusions: TaVNS is safe in healthy adults, and specific frequency and pulse width combinations can acutely enhance overall HRV, as reflected in SDNN, but do not affect vagally mediated HRV, as reflected by the RMSSD. Future studies should optimize taVNS parameters to maximize physiological and clinical outcomes. Full article

Background: Despite the vast evidence of the beneficial effect of vagus nerve stimulation on the course of myocardial infarction confirmed in studies using animal models, the introduction of this method into actual clinical practice remains uncommon. Objective: The objective of our study was to evaluate the effect of transcutaneous vagus nerve stimulation (tVNS) on in-hospital and long-term outcomes for patients with ST-elevation myocardial infarction. Materials and Methods: A blind, randomized, placebo-controlled clinical trial was conducted. The participants were randomly split into two groups. The Active tVNS group was subjected to stimulation of the tragus containing the auricular branch of the vagus nerve. The Sham tVNS group underwent stimulation of the lobule. Stimulation was performed immediately on admission before the start of the percutaneous coronary intervention (PCI). Then, tVNS continued throughout the entire PCI procedure and 30 min after its completion. The primary endpoints were hospital mortality and 12-month mortality. The secondary endpoints were in-hospital and remote non-lethal cardiovascular events. The combined endpoint consisted of major adverse cardiovascular events (MACEs)—recurrent myocardial infarction, stroke/TIA, and overall mortality. Results: A total of 110 patients were randomized into the Active tVNS group (n = 55) and the Sham tVNS group (n = 55). The incidences of hospital mortality, cardiogenic shock, and AV block 3 were statistically less common in the Active tVNS group than in the Sham tVNS group (p = 0.024*, p = 0.044*, and p = 0.013*, respectively). In the long-term period, no statistical differences were found in the studied outcomes obtained following the construction of Kaplan–Meyer survival curves. When comparing groups by total mortality, taking into account hospital mortality, we observed a tendency for the survival curves to diverge (Logrank test, p = 0.066). Statistical significance was revealed by the composite endpoint, taking into account hospital events (Logrank test, p = 0.0016*). Conclusions: tVNS significantly reduced hospital mortality (p = 0.024*), the level of markers of myocardial damage, and the frequency of severe cardiac arrhythmias in patients with acute myocardial infarction. In the long term, the prognostic value of tVNS was revealed by the composite endpoint major adverse cardiovascular events. Further studies with an expanded sample are needed for a more detailed verification of the data obtained to confirm the effectiveness of tVNS and allow an in-depth analysis of the safety and feasibility of its use in routine clinical practice. This clinical trial is registered with ClinicalTrials database under a unique identifier: NCT05992259. Full article

This paper presents a study undertaken to evaluate the sensor systems that were shortlisted to be used in the development of a portable respiratory-gated transcutaneous auricular vagus nerve stimulation (taVNS) system. To date, all published studies assessing respiratory-gated taVNS have been performed in controlled laboratory environments. This limitation arises from the reliance on non-portable sensing equipment, which poses significant logistical challenges. Therefore, we recognised a need to develop a portable sensor system for future research, enabling participants to perform respiratory-gated stimulation conveniently from their homes. This study aimed to measure the accuracy of an in-ear and a fingertip-based photoplethysmography (PPG) sensor in measuring cardiac vagal tone relevant heart rate variability (HRV) parameters of root mean square of successive R-R interval differences (RMSSDs) and the high-frequency (HF) component of HRV. Thirty healthy participants wore the prototype sensor equipment and the gold standard electrocardiogram (ECG) equipment to record beat-to-beat intervals simultaneously during 10 min of normal breathing and 10 min of deep slow breathing (DSB). Additionally, a stretch sensor was evaluated to measure its accuracy in detecting exhalation when compared to the gold standard sensor. We used Bland–Altman analysis to establish the agreement between the prototypes and the ECG system. Intraclass correlation coefficients (ICCs) were calculated to establish consistency between the prototypes and the ECG system. For the stretch sensor, the true positive rate (TPR), false positive rate (FPR), and false negative rate (FNR) were calculated. Results indicate that while ICC values were generally good to excellent, only the fingertip-based sensor had an acceptable level of agreement in measuring RMSSDs during both breathing phases. Only the fingertip-based sensor had an acceptable level of agreement during normal breathing in measuring HF-HRV. The study highlights that a high correlation between sensors does not necessarily translate into a high level of agreement. In the case of the stretch sensor, it had an acceptable level of accuracy with a mean TPR of 85% during normal breathing and 95% during DSB. The results show that the fingertip-based sensor and the stretch sensor had acceptable levels of accuracy for use in the development of the respiratory-gated taVNS system. Full article

Acute mental stress is a common experience in daily life, significantly affecting both physiological and psychological well-being. While traditional pharmacological interventions can be effective, they often accompany undesirable side effects. Non-pharmacological alternatives, such as non-invasive transcutaneous peripheral neuromodulation, have promise in mitigating acute stress-induced arousal, possibly with fewer side effects. Median nerve stimulation (MNS) and auricular vagus nerve stimulation (AVNS), in particular, have demonstrated notable potential. However, efficacy and mechanism of action pertaining to MNS and AVNS remain largely unknown. This paper comparatively investigated MNS and AVNS in terms of efficacy and mechanism of action in the context of mitigating acute stress-induced arousal. Using an experimental dataset collected from 19 healthy participants who experienced acute mental stressors as well as MNS and AVNS, we showed that (i) MNS and AVNS are both effective in mitigating acute stress-induced cardiovascular arousal with MNS modestly superior to AVNS in terms of a synthetic multi-modal variable derived from physio-markers representing heart rate, blood pressure, stroke volume, cardiac output, and peripheral vasoconstriction: 74% vs. 71% in explainability; 86% vs. 69% in stimulation consistency; 0.77 vs. 0.40 in stimulation sensitivity; and 34% vs. 19% in stimulation effectiveness, respectively; and that (ii) MNS and AVNS mitigate acute stress-induced cardiovascular arousal in a distinct mechanism of action: MNS primarily mitigates the arousal pertaining to the physio-markers representing heart rate and peripheral vasoconstriction, while AVNS mitigates the arousal pertaining to the physio-markers representing heart rate, blood pressure, stroke volume, cardiac output, and peripheral vasoconstriction. These findings may help to support future device development for addressing acute mental stress-induced arousal through MNS or AVNS, and they pave the way toward a better understanding of how to quantify the efficacy of such interventions. Full article

Background/Objectives: We aimed to examine the acute effects of deep breathing exercise and transcutaneous auricular vagus nerve stimulation (taVNS) on autonomic nervous system activation and the characteristics of certain muscle groups and to compare these two methods. Methods: 60 healthy adults between the ages of 18 and 45 were randomly divided into two groups to receive a single session of taVNS and deep breathing exercises. Acute measurements of pulse, blood pressure, perceived stress scale, autonomic activity, and muscle properties were performed before and after the application. Results: A significant decrease was detected in the findings regarding the perceived stress scale, pulse, and blood pressure values as a result of a single session application in both groups (p < 0.05). In addition, it was determined that the findings regarding autonomic measurement values increased in favor of the parasympathetic nervous system in both groups (p < 0.05). In measurements of the structural properties of the muscle, the stiffness values of the muscles examined in both groups decreased (p < 0.05), while the findings regarding relaxation increased (p < 0.05), except for the masseter in the deep breathing (DB) group. As a result of the comparative statistical evaluation between the groups, the increase in parasympathetic activity was found to be greater in the DB group according to root mean square of differences in successive RR intervals (RMSSD), the percent of differences in adjacent RR intervals > 50 ms (pNN50), and stress index parameters (p < 0.05). In the measurements made with the Myoton^®PRO device, the increase in the relaxation value was higher in the gastrocnemius muscle of the VNS group (p < 0.05). Conclusions: It has been observed that both methods can increase parasympathetic activity and muscle relaxation in healthy people in a single session. However, DB appears to be slightly superior in increasing parasympathetic activity, and VNS appears to be slightly superior in increasing relaxation. Full article

Background: The role of autonomic nervous system (ANS) modulation in chronic neck pain remains elusive. Transcutaneous vagus nerve stimulation (t-VNS) provides a novel, non-invasive means of potentially mitigating chronic neck pain. This study aimed to assess the effects of ANS modulation on heart rate variability (HRV), pain perception, and neck disability. Methods: In this double-blind randomized clinical trial, 102 participants with chronic neck pain were randomly allocated to one of three groups: t-VNS plus standard-care physiotherapy (SC-PT), heart rate variability biofeedback (HRV-BF) with SC-PT, or SC-PT alone. Interventions were administered three times weekly for 6 weeks. The following outcome measures were assessed at baseline and after 6 weeks: HRV, the visual analog scale (VAS), the pressure pain threshold (PPT), and the neck disability index (NDI). Results: The t-VNS group exhibited significant improvements compared to the HRV-BF and SC-PT groups. Specifically, t-VNS increased the RR interval (mean difference [MD] = 35.0 ms; p = 0.037) and decreased the average heart rate (MD = −5.4 bpm; p = 0.039). Additionally, t-VNS reduced the VAS scores (versus HRV-BF: MD = −0.8 cm, p = 0.044; SC-PT: MD = −0.9 cm, p = 0.018), increased the PPT (versus HRV-BF: MD = 94.4 kPa, p < 0.001; SC-PT (MD = 56.2 kPa, p = 0.001)), and lowered the NDI scores (versus HRV-BF: MD = −4.0, p = 0.015; SC-PT: MD = −5.9, p < 0.001). Conclusions: t-VNS demonstrated superior effectiveness compared to HRV-BF and SC-PT in regulating HRV, alleviating pain, and enhancing functional capabilities in individuals with chronic neck pain. 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

Background/Objectives: Chronic low back pain (CLBP) is a common condition with limited long-term treatment options. Vagus nerve stimulation (VNS) has shown potential for pain improvement, but its use in CLBP remains underexplored. Our aim was to evaluate the efficacy, feasibility and tolerability of transcutaneous auricular vagus nerve stimulation (taVNS) in reducing pain and improving functional outcomes in CLBP patients. Methods: Thirty adults with CLBP (VAS ≥ 40/100) participated in this open-label pilot study (NCT05639270). Patients were treated with a taVNS device on the left ear for 30 min daily over a period of 3 months. The primary outcome was a reduction in pain intensity (VAS) at 1 month. Secondary outcomes included pain intensity at 3 months, disability (Oswestry Disability Index, ODI), quality of life (EQ-5D-5L), catastrophizing and psychological distress. In addition, compliance and adverse events were monitored. Results: After 1 month, 27 patients were evaluated. VAS scores decreased significantly by 16.1 (SD = 17.9) mm (p < 0.001) and by 22.5 (25) mm (p < 0.001) after 3 months (24 patients were analyzed). Functional disability improved with an average reduction in ODI of 11.9 (11.1) points (p < 0.001) after 3 months. Other patient-reported outcomes also improved significantly over the 3-month period. Overall, 51.9% of the patients achieved clinically meaningful pain reduction (≥20 mm), and no serious adverse events were reported. Treatment adherence was good, with half of the patients achieving 80% adherence. Conclusions: This pilot study suggests that taVNS is a feasible, safe and potentially effective treatment for CLBP that warrants further investigation in a randomized controlled trial compared to sham stimulation. Full article

A new therapeutic approach, known as neuromodulation therapy—which encompasses a variety of interventional techniques meant to alter the nervous system in order to achieve therapeutic effects—has emerged in recent years as a result of advancements in neuroscience. Currently used methods for neuromodulation include direct and indirect approaches, as well as invasive and non-invasive interventions. For instance, the two primary methods of stimulating the vagus nerve (VN) are invasive VN stimulation (iVNS) and transcutaneous VN stimulation (tVNS). Since the latter is non-invasive, basic, clinical, and translational studies have focused on transcutaneous auricular VN stimulation (taVNS), the primary tVNS therapy, because of its advantages over iVNS, including ease of use, greater accessibility, and a lower side effect profile. taVNS is currently used as a novel neuromodulatory application to treat cardiovascular, mental, and autoimmune diseases. Future applications of this non-invasive neuromodulation technology to conditions like atrial fibrillation (AF) or ischemic stroke are highly likely due to its advancement. Full article

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is effective in regulating mood and high-level cognition in patients with major depressive disorder (MDD). This study aimed to investigate the efficacy of taVNS treatment in patients with MDD and an altered brain topological organization of functional networks. Methods: Nineteen patients with MDD were enrolled in this study. Patients with MDD underwent 4 weeks of taVNS treatments; resting-state functional magnetic resonance imaging (rs-fMRI) data of the patients were collected before and after taVNS treatment. The graph theory method and network-based statistics (NBS) analysis were used to detect abnormal topological organizations of functional networks in patients with MDD before and after taVNS treatment. A correlation analysis was performed to characterize the relationship between altered network properties and neuropsychological scores. Results: After 4 weeks of taVNS treatment, patients with MDD had increased global efficiency and decreased characteristic path length (Lp). Additionally, patients with MDD exhibited increased nodal efficiency (NE) and degree centrality (DC) in the left angular gyrus. NBS results showed that patients with MDD exhibited reduced connectivity between default mode network (DMN)–frontoparietal network (FPN), DMN–cingulo-opercular network (CON), and FPN–CON. Furthermore, changes in Lp and DC were correlated with changes in Hamilton depression scores. Conclusions: These findings demonstrated that taVNS may be an effective method for reducing the severity of depressive symptoms in patients with MDD, mainly through modulating the brain’s topological organization. Our study may offer insights into the underlying neural mechanism of taVNS treatment in patients with MDD. Full article