Cervical Vagus Research Articles

Use of laryngeal muscle evoked potential recording for experimental vagus nerve stimulation.

The laryngeal muscle evoked potential (LMEP) is a neurophysiological outcome parameter that guarantees integrity of the nerve-electrode interface during experiments with vagus nerve stimulation (VNS). This paper discusses a large series of minimally invasive LMEP recordings in 46 female Lewis rats, implanted with a custom-made VNS electrode around the left cervical vagus nerve. After a 3-week recovery, LMEPs were recorded twice in each animal, with swapping the anode and cathode positions of the VNS electrode (polarity inversion). A VNS-induced LMEP was identified as the initial negative peak wave post-stimulation artifact, consistently recorded in all sweeps at a given stimulation output current. Latency was defined as the time from stimulation onset to this negative peak, and stimulation threshold as the lowest current showing a clear and reproducible LMEP. An LMEP response was shown by 37/46 animals (80.4%), with stimulation intensity threshold of 0.37 ± 0.27 mA and latency of 2.39 ± 0.45 ms. Administering the cathodic pulse phase first at the caudal electrode contact resulted in the shortest LMEP latencies (MWU: p = 0.049. 2.36 ± 0.43 ms vs. 2.41 ± 0.47 ms). Minimally invasive LMEP recording provides a feasible and reliable means for checking electrode functioning and correct implantation.

Effect and Mechanism of Vagal Nerve Stimulation on Gastric Motility: A Preliminary Rodent Study.

Patients with functional dyspepsia often exhibit gastrointestinal motor disorders associated with gastric myoelectrical dysrhythmia. This study investigated the effects of vagal nerve stimulation (VNS) in a rodent model of gastric slow-wave dysrhythmia induced by colorectal distention (CRD). Male Sprague-Dawley rats were implanted with wires in the gastric body to record gastric slow waves and in the left cervical vagal nerve for stimulation. VNS was conducted over six sessions to optimize its efficacy on CRD-induced gastric dysrhythmia: control, CRD, and CRD with four different sets of parameters varying in frequency and stimulation on/off times. Both the CRD and VNS were conducted throughout the recording after the meal. Atropine was administered in two additional sessions, with or without VNS, to explore the involvement of the cholinergic pathway. The percentage of postprandial normal gastric slow waves (NSW), defined as the percentage of time during which the gastric slow wave was normal, was quantified using adaptive spectral analysis. The study findings were 1) CRD significantly reduced the percentage of NSW from 89.2%± 1.6% to 64.3%± 3.5% (p< 0.001), which was mitigated by VNS at 14 Hz (83.5%± 3.0%, p< 0.001) and 25 Hz (88.4%± 1.7%, p< 0.001); 2) atropine slightly, but not significantly, decreased the percentage of NSW to 54.1%± 3.2% and abolished the beneficial effects of VNS at 25 Hz on gastric slow waves (60.9%± 3.3%, p< 0.01); and 3) CRD delayed gastric emptying, which was restored by 25 Hz VNS. VNS using optimal parameters effectively ameliorated CRD-induced gastric dysmotility mediated through the vagal-cholinergic pathway, suggesting that VNS may hold therapeutic potential for functional gastrointestinal disorders.

Method for measuring cervical vagal nerve activity in conscious rats.

The current study aimed to propose a method to directly measure right cervical vagal nerve activity (cVNA) alongside renal sympathetic nerve activity (RSNA) in conscious rats. The right cervical vagus nerve was surgically exposed and fitted with a bipolar electrode to record cVNA. A microcatheter was used to administer levobupivacaine to selectively block afferent cVNA. Upon levobupivacaine administration, cVNA reduced by 84%, enabling the exclusive assessment of efferent cVNA. Intravenous and intraperitoneal administration of cholecystokinin-8 (CCK-8) demonstrated that peripherally acting CCK-8 influences the central nervous system through afferent cVNA without affecting the RSNA or efferent cVNA. This technique can be highly applicable for quantifying the dynamic changes in the interaction between vagal and sympathetic nerve activities, thereby shedding light on their roles in maintaining homeostasis and developing autonomic dysfunction, as in obesity and diabetes.

Unusual Surgical Resection of Asymptomatic Schwannoma of the Cervical Vagus Nerve With Risk of Stroke: Case Report

Unusual Surgical Resection of Asymptomatic Schwannoma of the Cervical Vagus Nerve With Risk of Stroke: Case Report

Postauricular Approach for Enucleation of Cervical Vagal Schwannomas.

This study evaluates the outcomes of intracapsular enucleation using the retroauricular hairline incision (RAHI) approach for treating cervical vagal schwannomas. A longitudinal study was conducted on patients with cervical vagal schwannomas. Eleven patients who underwent RAHI-based enucleation were included. Preoperative imaging was performed using contrast-enhanced MRI. Postoperative evaluations assessed pain, neurological function, cosmetic outcomes, voice, and swallowing functions. Eleven patients underwent surgery. The median tumor size was 4.6 cm. The median operation time was 42 min, with minimal bleeding. Common complications were earlobe numbness (45%) and temporary vocal cord paralysis (27%), which were resolved within a year. Cosmetic satisfaction was high, with median VAS scores of nine for scars and 10 for facial deformities. No significant dysphagia was found. No recurrences were observed over a median follow-up of 79 months. Intracapsular enucleation using the RAHI approach is a safe and effective method for treating cervical vagal schwannomas.

Optogenetic inhibition of the locus coeruleus blocks vagus nerve stimulation-induced enhancement of extinction of conditioned fear in rats.

Vagus nerve stimulation (VNS) is a therapeutic intervention previously shown to enhance fear extinction in rats. VNS is approved for use in humans for the treatment of epilepsy, depression, and stroke, and it is currently under investigation as an adjuvant to exposure therapy in the treatment of PTSD. However, the mechanisms by which VNS enhances extinction of conditioned fear remain unresolved. VNS increases norepinephrine levels in extinction-related pathways, but recent studies indicate that norepinephrine release from the locus coeruleus interferes with extinction learning. The purpose of this study is to elucidate the role of the locus coeruleus (LC) in VNS-enhanced fear extinction. Adult male and female tyrosine hydroxylase (Th)-Cre rats were implanted with a stimulating cuff electrode around the left cervical vagus nerve, and a Cre-dependent viral vector expressing the inhibitory opsin ArchT3.0 was infused bilaterally into the LC. Rats then underwent auditory fear conditioning followed by extinction training. During extinction training, rats were divided into four treatment groups: Sham stimulation, Sham with LC inhibition, VNS, and VNS with LC inhibition. Consistent with previous findings, VNS treatment during extinction training significantly reduced freezing 24 h and 2 weeks later. This effect was blocked by optogenetic LC inhibition, suggesting that VNS enhances extinction by engaging the LC.

Intraneural Device for Electrostimulation of Vagus Nerve in Rats: A Feasibility Study for Modulating Glucose Tolerance

ObjectivesThis study introduces EMPATIC (Electro-Modulation of PAncreaTic Islet Cells), a miniaturized intraneural device designed for transversal insertion into small nerves with a mean diameter of 400 μm. EMPATIC aims to modulate glucose tolerance through intraneural vagus nerve stimulation (VNS) in rats. Materials and MethodsEMPATIC design was optimized to fit into the cervical vagus nerve of rats and was developd through thin film microtechnologies. We evaluated the efficacy of the stimulation protocol (200 μA for 10 μs at 1 Hz) on glucose tolerance after intraperitoneal injection of glucose in three rat groups: control (no implant), sham (EMPATIC implant, no stimulation), and VNS (EMPATIC implant with stimulation). ResultsEMPATIC treatment in the VNS group significantly affected glucose tolerance tests compared with control and sham groups. The glucose tolerance test's area under the curve was 17,652 ± 913 mg∗min/dL in the control group, 16,929 ± 765 mg∗min/dL in the sham group, and reduced to 12,749 ± 1,075 mg∗min/dL in the stimulated group with statistical significance (p < 0.05 stimulated vs sham group, p < 0.05 stimulated vs control group). Blood glucose and insulin levels were measured, also under fasting conditions, for control and VNS groups, producing no statistically significant difference. ConclusionsEMPATIC treatment is effective in hyperglycemic conditions after glucose intake. No significant effects were observed when VNS was applied under fasting conditions. This study indicated the suitability of applying thin-film intrafascicular electrodes for transversal insertion into small nerves (mean diameter of 400 μm), which, to the best of our knowledge, represents an advancement over the state of the art. It also establishes the feasibility of investigating neural pathways related to glucose homeostasis using invasive intraneural electrodes in the right cervical vagus nerve of rats.

Vagal stimulation ameliorates murine colitis by regulating SUMOylation.

Inflammatory bowel diseases (IBDs) are chronic debilitating conditions without cure, the etiologies of which are unknown, that shorten the lifespans of 7 million patients worldwide by nearly 10%. Here, we found that decreased autonomic parasympathetic tone resulted in increased IBD susceptibility and mortality in mouse models of disease. Conversely, vagal stimulation restored neuromodulation and ameliorated colitis by inhibiting the posttranslational modification SUMOylation through a mechanism independent of the canonical interleukin-10/α7 nicotinic cholinergic vagal pathway. Colonic biopsies from patients with IBDs and mouse models showed an increase in small ubiquitin-like modifier (SUMO)2 and SUMO3 during active disease. In global genetic knockout mouse models, the deletion of Sumo3 protected against development of colitis and delayed onset of disease, whereas deletion of Sumo1 halted the progression of colitis. Bone marrow transplants from Sumo1-knockout (KO) but not Sumo3-KO mice into wild-type mice conferred protection against development of colitis. Electric stimulation of the cervical vagus nerve before the induction of colitis inhibited SUMOylation and delayed the onset of colitis in Sumo1-KO mice and resulted in milder symptoms in Sumo3-KO mice. Treatment with TAK-981, a first-in-class inhibitor of the SUMO-activating enzyme, ameliorated disease in three murine models of IBD and reduced intestinal permeability and bacterial translocation in a severe model of the disease, suggesting the potential to reduce progression to sepsis. These results reveal a pathway of vagal neuromodulation that reprograms endogenous stress-adaptive responses through inhibition of SUMOylation and suggest SUMOylation as a therapeutic target for IBD.

Cervical Vagal Schwannoma: A Case Report

Nerve sheath tumors arising from the cervical vagus nerve are rare. These tumors mostly present as asymptomatic, slowly growing masses in the lateral neck. The authors reported a case of vagal schwannoma in a healthy male patient with a small lump in his neck. The neck examination revealed a firm, non-tender, non-pulsatile mass measuring 3×3 cm in the upper part of the right neck at the level of the carotid bifurcation. No neurologic deficit was detected. Fine needle aspiration showed inconclusive results. The MRI findings were distinctive, enabling a diagnosis before surgery. The preferred treatment option was gross total resection while preserving the vagus nerve. Although the authors meticulously dissected the tumor from the nerve and the nerve trunk was preserved, postoperative complications of this case were ipsilateral vocal cord paralysis and hypoglossal nerve palsy. Complete surgical removal is crucial to prevent recurrence. The prognosis of the complete cure for benign neurogenic tumors in the neck is excellent.

Laterality, sexual dimorphism, and human vagal projectome heterogeneity shape neuromodulation to vagus nerve stimulation

Neuromodulation by vagus nerve stimulation (VNS) provides therapeutic benefits in multiple medical conditions, including epilepsy and clinical depression, but underlying mechanisms of action are not well understood. Cervical vagus nerve biopsies were procured from transplant organ donors for high resolution light microscopy (LM) and transmission electron microscopy (TEM) to map the human fascicular and sub-fascicular organization. Cervical vagal segments show laterality with right sided dominance in fascicle numbers and cross-sectional areas as well as sexual dimorphism with female dominance in fascicle numbers. The novel and unprecedented detection of numerous small fascicles by high resolution LM and TEM expand the known fascicle size range and morphological diversity of the human vagus nerve. Ground truth TEM quantification of all myelinated and unmyelinated axons within individual nerve fascicles show marked sub-fascicular heterogeneity of nerve fiber numbers, size, and myelination. A heuristic action potential interpreter (HAPI) tool predicts VNS-evoked compound nerve action potentials (CNAPs) generated by myelinated and unmyelinated nerve fibers and validates functional dissimilarity between fascicles. Our findings of laterality, sexual dimorphism, and an expanded range of fascicle size heterogeneity provide mechanistic insights into the varied therapeutic responses and off-target effects to VNS and may guide new refinement strategies for neuromodulation.

A Rare Case of Cervical Vagus Nerve Schwannoma in an Adult Patient: Diagnostic and Therapeutic Strategy

A Rare Case of Cervical Vagus Nerve Schwannoma in an Adult Patient: Diagnostic and Therapeutic Strategy

First-in-human microelectrode recordings from the vagus nerve during clinical vagus nerve stimulation.

Vagus nerve stimulation (VNS) is an effective treatment for people with drug-resistant epilepsy. However, its mechanisms of action are poorly understood, including which nerve fibers are activated in humans during VNS in typical clinical settings and which are required for clinical efficacy. In particular, there have been no intraneural recordings of vagus nerve fiber activation in awake humans undergoing chronic VNS. In this study, for the first time, we report recordings from the vagus nerve in this setting. The recordings were performed using a sterile tungsten microelectrode inserted percutaneously into the cervical vagus nerve under ultrasound guidance. The clinical VNS systems were used to deliver stimulation while activity in the vagus nerve was recorded. In addition to activating myelinated axons at low currents, we provide evidence that VNS can also activate unmyelinated C fibers in the vagus nerve at currents <1 mA. These results add to our understanding of how VNS exerts its beneficial effects in drug-resistant epilepsy. Here we describe for the first time, electrical recordings from the vagus nerve in awake drug-resistant epilepsy patients with an implanted vagus nerve stimulation (VNS) device. We found that the VNS device was able to activate both myelinated and unmyelinated fibers within the vagus nerve, whichcontributes to our understanding of how VNS works in the context of drug-resistant epilepsy.

Neck triangle nerve enlargement in hereditary transthyretin amyloidosis correlates with changes in the autonomic, cardiac, and gastrointestinal systems.

Hereditary transthyretin amyloidosis (ATTRv) is a hereditary disease that affects multiple bodily systems. Although sonography generally reveals enlargement of nerves in the limbs, the brachial plexus, and vagus nerve, the clinical significance of these findings remains unclear. We performed sonographic measurements of the median nerve, cervical spinal nerves at the C5-C7 level, and the vagus nerve in patients with ATTRv and healthy controls. Clinical profiles and cardiac and gastrointestinal examination results were also collected for linear regression analysis. We recruited 47 patients with ATTRv (males/females: 34/13, age: 65.6±5.3 years). The sampled segments were all significantly larger than those of the controls. In the clinical profiles, the sum of the Z scores of the neck triangle nerves (cervical spinal nerves and vagus nerve) and of all nerves (cervical spinal nerves, vagus nerve, and median nerve at the wrist) significantly correlated with the familial amyloid polyneuropathy stage, onset of autonomic nervous system (ANS) symptoms, and autonomic symptom scores. On cardiac examinations, several ultrasonography and magnetic resonance imaging parameters (primarily those that reflect heart volume) were found to be significantly correlated with the sum of the Z scores of the cervical spinal nerves but not with the Z score of the vagus nerve. In gastrointestinal evaluation, the cross-sectional area of the vagus nerve was correlated with gastric emptying time parameters on scintigraphy. Neck triangle nerve enlargement on sonography correlated with parameters related to ANS dysfunction, indicating that nerve enlargement observed on ultrasonography may serve as a potential surrogate biomarker of ATTRv.

Ancient cervical vagal schwannoma and an interposition great auricular to vagus nerve graft

Introduction: Schwannomas of the cervical vagus nerve are exceedingly rare and have a myriad of clinical presentations depending on the tumor size and its proximity to neurovascular structures. We report a rare case of a cervical vagal schwannoma that was successfully treated with en bloc resection and reconstruction with a great auricular to vagus nerve graft. Case Report: A 42-year-old male presented with an asymptomatic, right lateral neck mass. Magnetic resonance imaging revealed a lesion 2.4 cm × 1.4 cm × 4.0 cm in size, located between the carotid arteries and internal jugular vein displacing the internal carotid artery anteromedially. En bloc resection of the lesion and reconstruction of the vagus nerve with a great auricular interposition graft was performed. Conclusion: Vagal schwannomas are rare, benign neurogenic tumors. Complete surgical excision is the mainstay of treatment. When a safe surgical plane cannot be identified between the neurogenic tumor and the main nerve trunk, en bloc resection with reconstruction should be considered.

Atypical Presentation and Postoperative Management of Vagal Nerve Tumors.

Tumors involving the vagus nerve are often clinically silent. We offer a case series with different clinical presentations and distinctive post-surgical sequelae that highlight some of the challenges associated with managing cervical vagal nerve tumors. Single-institution, retrospective review of patients with tumors involving the vagus nerve. We describe clinical presentations and postoperative sequelae of five patients who underwent surgical management of vagal nerve pathology with atypical presentation or subsequent clinical course. Here, we present five patients treated at our institution for vagal tumors. In four of the five patients, the presenting symptoms resolved after surgery. Two patients presented with intractable neurogenic cough, and another two presented with autonomic symptoms, one with syncope/palpitations and the other with intractable sweating. The final patient presented with a rapidly enlarging vagal paraganglioma and developed intractable cough after resection. We present two patients with novel approach to vagal paragangliomas that underwent ligation of feeding blood supply without removing the tumor, resulting in resolution of an intractable cough in one patient and resolution of severe nighttime sweating in the other. Management of tumors associated with the cervical vagus nerve that present with symptoms or rapid growth poses a clinical dilemma. Consideration of the tumor origin with either enucleation of schwannomas or ligation of feeding vessels may preserve function while addressing the presenting symptoms.

Firing properties of single axons with cardiac rhythmicity in the human cervical vagus nerve.

Microneurographic recordings of the human cervical vagus nerve have revealed the presence of multi-unit neural activity with measurable cardiac rhythmicity. This suggests that the physiology of vagal neurones with cardiovascular regulatory function can be studied using this method. Here, the activity of cardiac rhythmic single units was discriminated from human cervical vagus nerve recordings using template-based waveform matching. The activity of 44 cardiac rhythmic neurones (22 with myelinated axons and 22 with unmyelinated axons) was isolated. By consideration of each unit's firing pattern with respect to the cardiac and respiratory cycles, the functional identification of each unit was attempted. Of note is the observation of seven cardiac rhythmic neurones with myelinated axons whose activity was recruited or enhanced by slow, deep breathing, was maximal during the nadir of respiratory sinus arrhythmia, and showed an expiratory peak. This is characteristic of cardioinhibitory efferent neurones, which are responsible for respiratory sinus arrhythmia. The remaining 15 cardiac rhythmic neurones with myelinated axons were categorised as cardiopulmonary receptors or arterial baroreceptors based on the position of their peak in firing with respect to the R-wave of the cardiac cycle. This latter method is not viable for neurones with unmyelinated axons due to their slow and unknown conduction velocities. With the exception of three neurones whose expiratory modulation implicates them as cardiac-projecting efferent neurones, this population is likely dominated by arterial baroreceptors. In conclusion, the activity of single units with cardiovascular function has been discriminated within the human cervical vagus, enabling their systematic study. KEY POINTS: Recordings of the electrical activity of the vagus nerve have recently been made at the level of the neck in humans. Examination of the gross activity of this nerve reveals subpopulations of neurones whose activity fluctuates in time with the heart's beat, suggesting that the neurones that monitor or modify cardiac function can be studied using this method. Here, the activity of individual cardiac rhythmic neurones was isolated from human vagus nerve recordings using template-based spike sorting. The relationship between this activity and the cardiac and respiratory cycles was used as a means of classifying each neurone. Neuronal firing patterns that are consistent with that of neurones that modify cardiac function, including heart-slowing 'cardioinhibitory' neurones, as well as neurones that inform the brain of cardiovascular status were observed. This approach enables, for the first time, the systematic study of the function of these neurones in humans in both health and disease.

Towards spatially selective efferent neuromodulation: anatomical and functional organization of cardiac fibres in the porcine cervical vagus nerve.

Spatially selective vagus nerve stimulation (sVNS) offers a promising approach for addressing heart disease with enhanced precision. Despite its therapeutic potential, VNS is limited by off-target effects and the need for time-consuming titration. Our research aimed to determine the spatial organization of cardiac afferent and efferent fibres within the vagus nerve of pigs to achieve targeted neuromodulation. Using trial-and-error sVNS in vivo and ex vivo micro-computed tomography fascicle tracing, we found significant spatial separation between cardiac afferent and cardiac efferent fibres at the mid-cervical level and they were localized on average on opposite sides of the nerve cross-section. This was consistent between both in vivo and ex vivo methods. Specifically, cardiac afferent fibres were located near pulmonary fibres, consistent with findings of cardiopulmonary convergent circuits and, notably, cardiac efferent fascicles were exclusive. These cardiac efferent regions were located in close proximity to the recurrent laryngeal regions. This is consistent with the roughly equitable spread across the nerve of the afferent and efferent fibres. Our study demonstrated that targeted neuromodulation via sVNS could achieve scalable heart rate decreases without eliciting cardiac afferent-related reflexes; this is desirable for reducing sympathetic overactivation associated with heart disease. These findings indicate that understanding the spatial organization of cardiac-related fibres within the vagus nerve can lead to more precise and effective VNS therapy, minimizing off-target effects and potentially mitigating the need for titration. KEY POINTS: Spatially selective vagus nerve stimulation (sVNS) presents a promising approach for addressing chronic heart disease with enhanced precision. Our study reveals significant spatial separation between cardiac afferent and efferent fibres in the vagus nerve, particularly at the mid-cervical level. Utilizing trial-and-error sVNS in vivo and micro-computed tomography fascicle tracing, we demonstrate the potential for targeted neuromodulation, achieving therapeutic effects such as scalable heart rate decrease without stimulating cardiac afferent-related reflexes. This spatial understanding opens avenues for more effective VNS therapy, minimizing off-target effects and potentially eliminating the need for titration, thereby expediting therapeutic outcomes in myocardial infarction and related conditions.

Genetic labeling of the nucleus of tractus solitarius neurons associated with electrical stimulation of the cervical or auricular vagus nerve in mice

IntroductionVagus nerve stimulation (VNS) is clinically useful for treating epilepsy, depression, and chronic pain. Currently, cervical VNS (cVNS) treatment is well-established, while auricular VNS (aVNS) is under development. Vagal stimulation regulates functions in diverse brain regions; therefore, it is critical to better understand how electrically-evoked vagal inputs following cVNS and aVNS engage with different brain regions. ObjectiveAs vagus inputs are predominantly transmitted to the nucleus of tractus solitarius (NTS), we directly compared the activation of NTS neurons by cVNS or aVNS and the brain regions directly projected by the activated NTS neurons in mice. MethodsWe adopted the targeted recombination in active populations method, which allows for the activity-dependent, tamoxifen-inducible expression of mCherry—a reporter protein—in neurons specifically associated with cVNS or aVNS. ResultscVNS and aVNS induced comparable bilateral mCherry expressions in neurons within the NTS, especially in its caudal section (cNTS). However, the numbers of mCherry-expressing neurons within different subdivisions of cNTS was distinctive. In both cVNS and aVNS, anterogradely labeled mCherry-expressing axonal terminals were similarly observed across different areas of the forebrain, midbrain, and hindbrain. These terminals were enriched in the rostral ventromedial medulla, parabrachial nucleus, periaqueductal gray, thalamic nuclei, central amygdala, and the hypothalamus. Sex difference of cVNS- and aVNS-induced labeling of NTS neurons was modest. ConclusionThe central projections of mCherry-expressing cNTS terminals are comparable between aVNS and cVNS, suggesting that cVNS and aVNS activate distinct but largely overlapping projections into the brain through the cNTS.

Vagus nerve size determined via ultrasonography is associated with white matter lesions in patients with vascular risk factors

PurposeThe cross-sectional area (CSA) of the cervical vagus nerve (VN), as assessed through ultrasonography, might be linked to autonomic nervous system dysfunction. Hypertension is the primary factor associated with cerebral white matter lesions (WMLs), but there is also evidence of a connection with autonomic nervous system dysfunction. However, the associations between WMLs and VN size are unclear. Our objective was to investigate the associations between WMLs and VN size in patients with vascular risk factors.MethodsThe CSA of the VN was evaluated using carotid ultrasonography in patients with a history of stroke (acute or chronic) and comorbidities (n = 196, 70.2 ± 12.7 years). Common carotid artery (CCA) intima-media thickness and interadventitial diameter (IAD) were also measured. The severity of the WMLs was assessed by the Fazekas classification and Scheltens’ scale.ResultsThe CSA of the right VN (2.08 ± 0.65 mm2) was significantly greater than that of the CSA of the left VN (1.56 ± 0.44 mm2) (P < 0.001). Multiple linear regression analyses revealed that older age, hypertension, increased right CCA IAD, and decreased CSA of the right VN (standardized partial regression coefficient [β] − 0.226; P < 0.001) were independently associated with the severity of WMLs (Scheltens’ scale). A decreased CSA of the left VN was also associated with the severity of WMLs (β = − 0.239; P < 0.001).ConclusionVN size determined via ultrasonography was associated with the severity of WMLs. While these findings do not establish a causal relationship, they suggest that autonomic nervous system dysfunction is involved in the progression of WMLs.

Transcutaneous cervical vagus nerve stimulation enhances second-language vocabulary acquisition while simultaneously mitigating fatigue and promoting focus

Transcutaneous vagus nerve stimulation (tVNS) is a promising technique for enhancing cognitive performance and skill acquisition. Yet, its efficacy for enhancing learning rate and long-term retention in an ecologically valid learning environment has not been demonstrated. We conducted two double-blind sham-controlled experiments examining the efficacy of auricular tVNS (taVNS: Experiment (1) and cervical tVNS (tcVNS: Experiment (2), on a 5 day second-language vocabulary acquisition protocol among highly selected career linguists at the US Department of Defense’s premier language school. tcVNS produced accelerated recall performance during training (Day 2–4), benefits of which were maintained across a 24 h retention interval with no stimulation at the final test. Consistent with prior work, tcVNS also produced fatigue-mitigating and focus-promoting effects as measured by the Air Force Research Laboratory Mood Questionnaire. Based on the current and the previous findings supporting tVNS’ efficacy on performance, training enhancement, and fatigue mitigation, we believe tcVNS to be an effective learning acceleration tool that can be utilized at language-teaching and other institutions focused on intensive training of cognitive skills.