Search Results (157)

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

Vagal nerve stimulators (VNSs) improve seizure control in up to half of the patients who have them implanted. In non-responding patients, VNS removal may be necessary. Removal is traditionally accomplished through two incisions. We present our experience removing VNSs through a single incision. Background/Objectives: To determine if VNS removal can be safely performed through a single incision. Methods: The medical records of 73 consecutive patients who underwent VNS removal at our institution from 2012 to 2024 were reviewed. Patients were divided into single-incision and two-incision treatment groups. Operative time and surgical complications were compared between groups. Results: A total of 73 patients underwent VNS removal during the study timeframe. Forty-eight VNS removals were accomplished via a single incision, while 25 required both incisions. Time in the operating room was roughly half as long for single-incision removal vs. two-incision removal (29.4 min, range 11–84 vs. 74.2 min, range 33–203); however, single incision was initially attempted in all cases. In two of the incision cases, the neck dissection resulted in an injury to the internal jugular (IJ) vein. In one case, the IJ was repaired and the lead wire removed. In a second case, the IJ could not be repaired, and a segment of lead wire was retained. In a third case, a short length of lead wire was discovered after a single-incision removal and a second procedure was necessary for removal. There were no significant differences in the rates of transient vocal cord weakness, cough, and/or dysphagia between both treatment groups (p = 0.7368), and there were no cases of permanent nerve palsy. Conclusions: VNS removal can be safely accomplished via a single incision in most cases. Successful single-incision procedures may be shorter than the two-incision approach. Attempted VNS removal via a single incision may result in increased incidence of transient hoarseness, dysphagia, and/or cough, but may result in reduced rates of permanent injury or IJ injury. Full article

Background: Acute respiratory distress syndrome (ARDS) is a high-mortality disease strongly associated with an imbalance in the inflammatory response. The ratio of helper T 17 (Th17) cells to regulatory T (Treg) cells is significantly correlated with prognosis and outcomes in ARDS. Vagus nerve stimulation (VNS) alleviates lung injury in ARDS model rats. The objective of this study was to further investigate whether VNS attenuates lipopolysaccharide-induced ARDS by regulating Th17/Treg homeostasis and to explore the underlying mechanisms. Methods: We assessed the degree of lung injury using hematoxylin and eosin staining, the lung wet-to-dry ratio, and total protein and pro-inflammatory cytokine levels in bronchoalveolar lavage fluid. The expression levels of Th17 and Treg cells were determined using flow cytometry, Western blotting, quantitative real-time PCR, and enzyme-linked immunosorbent assays. Results: We found that VNS reduced lung injury in ARDS model rats. Additionally, VNS regulated Th17/Treg homeostasis and reduced the levels of inflammatory factors in both the lungs and spleens. Notably, the effects of VNS were consistent when the afferent or efferent vagus nerve, or both, were stimulated. Further investigation revealed that VNS upregulated splenic α7 nicotinic acetylcholine receptors (α7nAChRs). The administration of an α7nAChR agonist enhanced VNS-mediated regulation of Th17/Treg homeostasis and attenuated lung injury, while these effects were blocked by α7nAChR antagonists. Conclusions: Our study demonstrated that VNS regulates the Th17/Treg balance through α7nAChR activation in the spleen, thereby mitigating lung injury in ARDS. These findings provide new theoretical support for the use of VNS in attenuating ARDS. 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

Background/Objectives: Low-frequency alternating current (LFAC) has been shown to induce nerve conduction block (LFACb). However, the effects of LFAC on conduction delay prior to block remain unclear. This study investigates the impact of LFACb on conduction velocity and blocking thresholds in myelinated and unmyelinated fibers using experimental and computational models. Methods: Four models were employed to analyze LFACb effects: (1) in-vivo experiments in earthworms examined conduction delays across nerve bundles with distinct conduction velocities; (2) ex-vivo experiments in canine vagus nerves assessed the upstream and downstream effects of LFAC waveforms ranging from 50 mHz to 500 mHz; (3) in-silico simulations using the Horn, Yoshida, and Schild (HYS) model for unmyelinated fibers explored size-dependent conduction delays and blocking thresholds; and (4) in-silico simulations using the McIntyre, Richardson, and Grill (MRG) model extended to 504 Nodes of Ranvier characterized myelination effects, localized nodal interactions, and diameter-dependent thresholds. Results: LFAC-induced conduction delays were independent of LFAC frequency but strongly influenced by fiber diameter and conduction velocity. Larger fibers exhibited lower block thresholds and shorter delays before block onset. In contrast, smaller fibers demonstrated prolonged subthreshold conduction delays before achieving full block. Conclusions: These findings suggest that LFACb could serve as a neuromodulation tool for selectively blocking larger fibers while preserving smaller fiber function. This has potential applications in functional electrical stimulation (FES) and temporary, non-destructive nerve blocks for clinical and research applications. Full article

Background and Objectives: This study aimed to discuss positional changes in the sternocleidomastoid (SCM) muscle and vagus nerve with head position, their effect on the surgical path, positional variations, the selection of an appropriate position for surgery, their effects on the surgical procedure, and complications by using peroperative ultrasonography. Materials and Methods: Vagal nerve stimulation surgery patients over the age of 18 years were included. Peroperative ultrasonography images were scanned, and changes in head position and anatomical and positional variations in the SCM muscle and vagus nerve at the surgical incision level were examined. Results: SCM localization was most frequently observed in the lateral aspect of the carotid sheath (n:16) in neutral position, while it was mostly observed in the medial aspect of the carotid sheath (n:16) at a 15 degree rotation. The vagus nerve was mostly observed between the jugular vein and carotid artery in neutral position (n:21), and it was observed at the same position at a 15 degree rotation (n:17). The positional change of the SCM muscle with head position was found to be statistically significant (p < 0.001), while the positional change of the vagus nerve was not (p:0.198). Conclusions: The SCM muscle closes the surgical path with head rotation by either deviating over the carotid sheath or increasing its deviation. In addition to its anatomical variations, the vagus nerve shows different positional changes with head rotation. Deciding on the head position in vagal nerve stimulation surgery, using peroperative ultrasonography rather than a routine position, may be effective in reducing surgical time and possible complications. Full article

Psychiatric disorders and internal diseases frequently co-occur, posing significant challenges due to overlapping symptoms, shared pathophysiological mechanisms, and increased healthcare burdens. Neuroinflammation has emerged as a central mechanism linking these conditions, driven by systemic inflammation, hypothalamic–pituitary–adrenal (HPA) axis dysregulation, and autonomic nervous system (ANS) imbalance. This review synthesizes current evidence on the role of neuroinflammation in comorbid conditions such as depression, anxiety, cardiovascular disease, and diabetes mellitus, emphasizing bidirectional relationships and shared inflammatory pathways. This analysis identifies gaps in longitudinal studies, biomarker validation, and the integration of multidisciplinary care models. Emerging therapeutic approaches, including IL-6 inhibitors, vagus nerve stimulation, and behavioral interventions, show promise but remain underexplored in combined applications. Furthermore, disparities in research representation limit the generalizability of findings and highlight the need for inclusive clinical trials. Addressing these gaps through precision medicine, advanced biomarker monitoring technologies, and equitable healthcare strategies could transform the management of these complex comorbidities. By advancing our understanding of neuroinflammatory mechanisms and promoting integrated interventions, this review underscores the need for a collaborative, patient-centered approach to improve outcomes and reduce the global burden of psychiatric and internal disease comorbidities. Full article

Background/Objectives: Cerebral folate transporter deficiency is characterized by pauses and regression in general development stages, with ataxia, choreoathetoid movements, and myoclonic epilepsy generally resistant to treatment. The aim of this study was to comprehensively evaluate cases followed up in two centres in Türkiye for a diagnosis of folate receptor-α deficiency. Methods: The study included nine cases from six different families. Results: The patients comprised 22.2% males and there was parental consanguinity in 88.9% of cases. The mean age at which complaints were first noticed was 3.7 years, and the age of definitive diagnosis was 10.4 years. The most frequently seen first complaints were febrile convulsions and attention deficit-hyperactivity-learning difficulties. The diagnosis most commonly made before the definitive diagnosis was epilepsy, and the first seizure occurred at a mean of 5.2 years. On cranial imaging, white matter involvement, cerebellar atrophy and cerebral atrophy were determined most often. Definitive diagnosis was established solely through clinical findings and genetic analysis. Three different variants in the FOLR1 gene were determined. Treatment with folinic acid at a dose of 5.2 mg/kg/day of PO was started at the age of 9.8 years on average, and intravenous folinate was started at different doses. Conclusions: This study stands out as one of the largest case series in the literature and identifies a previously unreported novel variant. Our study suggests that FOLR1-related CFD should be considered in cases with febrile convulsions, developmental delay, ataxia, autism spectrum disorder, acquired microcephaly, and MRI findings of white matter involvement and cerebellar atrophy. Due to an asymptomatic early period, CFD diagnosis may be delayed, and treatment after symptom onset may be less effective. Incorporating FOLR1 gene analysis into newborn screening programmes could facilitate early diagnosis and treatment. It is thought that the application of vagus nerve stimulation, in addition to folinic acid and anticonvulsant drug treatment, could be effective in seizure control. 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

Background: The ongoing conflict in Ukraine has forced numerous migrants into neighboring countries, many suffering from pre-existing or newly acquired physical and mental health conditions. Addressing these complex challenges in humanitarian settings requires innovative, evidence-based interventions that are cost-effective and easy to administer. Drawing upon research highlighting the vagus nerve’s role in regulating well-being, we hypothesized that vagal nerve activation could offer a promising therapeutic approach. Method: We conducted a proof-of-concept study in which 21 Ukrainian forced migrants were trained in a biofeedback-guided paced breathing intervention designed to stimulate the vagus nerve and promote self-regulation of stress response systems. Changes in pain perception, perceived stress, blood pressure, and heart rate were assessed before and after the vagal breathing intervention using a t-test. Correlations were examined at baseline. Results: Statistically significant improvements were observed in all measures except systolic blood pressure, providing preliminary evidence for the efficacy of vagal nerve activation in alleviating stress-related health symptoms. Conclusions: This study demonstrates the feasibility and therapeutic potential of a vagal nerve-activating intervention in a humanitarian setting. These findings warrant replication in larger, controlled trials. If substantiated, this low-cost, scalable intervention could help mitigate health burdens among forced migrant populations worldwide. 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