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The identification of acute cardioprotective strategies against myocardial ischemia/reperfusion (I/R) injury that can be applied in the catheterization room is currently an unmet clinical need and several interventions evaluated in the past at the pre-clinical level have failed in translation. Autonomic imbalance, sustained by an abnormal afferent signalling, is a key component of I/R injury. Accordingly, there is a strong rationale for neuromodulation strategies, aimed at reducing sympathetic activity and/or increasing vagal tone, in this setting. In this review we focus on cervical vagal nerve stimulation (cVNS) and on transcutaneous auricular vagus nerve stimulation (taVNS); the latest has the potential to overcome several of the issues of invasive cVNS, including the possibility of being used in an acute setting, while retaining its beneficial effects. First, we discuss the pathophysiology of I/R injury, that is mostly a consequence of the overproduction of reactive oxygen species. Second, we describe the functional anatomy of the parasympathetic branch of the autonomic nervous system and the most relevant principles of bioelectronic medicine applied to electrical vagal modulation, with a particular focus on taVNS. Then, we provide a detailed and comprehensive summary of the most relevant pre-clinical studies of invasive and non-invasive VNS that support its strong cardioprotective effect whenever there is an acute or chronic cardiac injury and specifically in the setting of myocardial I/R injury. The potential benefit in the emerging field of post cardiac arrest syndrome (PCAS) is also mentioned. Indeed, electrical cVNS has a strong anti-adrenergic, anti-inflammatory, antioxidants, anti-apoptotic and pro-angiogenic effect; most of the involved molecular pathways were already directly confirmed to take place at the cardiac level for taVNS. Pre-clinical data clearly show that the sooner VNS is applied, the better the outcome, with the possibility of a marked infarct size reduction and almost complete left ventricular reverse remodelling when VNS is applied immediately before and during reperfusion. Finally, we describe in detail the limited but very promising clinical experience of taVNS in I/R injury available so far.

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Background: Transcutaneous Vagal Nerve Stimulation (tVNS) has been used as a promising noninvasive neuromodulation technique for the treatment of various systems.The aim of this study was to analyze the research hotspots and future directions of tVNS in the 21st century by using bibliometric methods. Methods: The study object was the literature related to tVNS from the Web of Science database from 2000 to May 2024. In order to measure and analyze the number of literature issuance, institutions, authors, countries, keywords, co-citations, and journals of publication, we used VOSviewer, Citespace, Bibliometrix R-package, and Scimago Graphica software. A narrative review of the current research content of tVNS was conducted to gain a better understanding of the current state of the field. Results: A total of 569 papers were included in the study. The results show that from 2000 to 2024, the number of publications shows an increasing trend year by year, involving a total of 326 research institutions. The United States, China, and Germany are the major research centers. The study identified 399 keywords, which roughly formed 11 natural clusters, revealing that the current hotspots of related research are mainly reflected in 3 areas: intervention efficacy on nervous system diseases, mechanism of action of tVNS, and stimulation mode of tVNS. The top 10 most cited references focus on research into the mechanism of action of tVNS. Conclusion: The efficacy and safety of tVNS have been confirmed in previous studies, but a standardized tVNS treatment protocol has not yet been developed, and most clinical studies have small sample sizes and lack multicenter and multidisciplinary collaboration. Currently, tVNS is used in the treatment of neurological diseases, psychiatric diseases, cardiovascular diseases, and some autoimmune diseases. It is expected that future research in this field will continue to focus on the application of tVNS in central nervous system diseases and the exploration of related mechanisms, and at the same time, with the rise of non-invasive neuromodulation technology, the application of tVNS in other diseases also has great potential for development.

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Allograft rejection, accompanied by a rise in proinflammatory cytokines, is a leading cause of morbidity and mortality after lung transplantation. Immunosuppressive treatments are routinely employed as an effective way to prevent rejection, however, there is still an unmet need to develop new strategies to reduce the damage caused to transplanted organs by innate inflammatory responses. Recent research has shown that activating the vagus nerve's efferent arm regulates cytokine production and improves survival in experimental conditions of cytokine excess, such as sepsis, hemorrhagic shock, ischemia-reperfusion injury, among others. The cholinergic anti-inflammatory pathway can provide a localized, fast, and discrete response to inflammation by controlling the neuroimmune response and preventing excessive inflammation. This review intends to assess and discuss, the influence of noninvasive vagal nerve stimulation for prophylactic measures and supporting treatment in patients undergoing organ transplantation rejection with a prominent T-cell mediated immune response as a means of attenuating inflammation and leukocyte infiltration of the graft vessels.

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Objective: Recent studies have shown that transcutaneous vagal nerve stimulation (tVNS) holds promise as a treatment for neurological or psychiatric disease through the ability to modulate neural activity in some brain regions without an invasive procedure. The objective of this study was to identify the neural correlates underlying the effects of tVNS. Methods: Twenty right-handed healthy subjects with normal hearing participated in this study. An auricle-applied tVNS device (Soricle, Neurive Co., Ltd., Gyeongsangnam-do, Republic of Korea) was used to administer tVNS stimulation. A session consisted of 14 blocks, including 7 blocks of tVNS stimulation or sham stimulation and 7 blocks of rest, and lasted approximately 7 min (1 block = 30 s). Functional magnetic resonance imaging (fMRI) was performed during the stimulation. Results: No activated regions were observed in the fMRI scans following both sham stimulation and tVNS after the first session. After the second session, tVNS activated two clusters of brain regions in the right frontal gyrus. A comparison of the activated regions after the second session of each stimulation revealed that the fMRI following tVNS exhibited four surviving clusters. Additionally, four clusters were activated in the overall stimulated area during both the first and second sessions. When comparing the fMRI results after each type of stimulation, the fMRI following tVNS showed four surviving clusters compared to the fMRI after sham stimulation. Conclusion: tVNS could stimulate some brain regions, including the fronto-parietal network. Stimulating these regions for treating neurological or psychiatric disease might require applying tVNS for at least 3.5 min.

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BACKGROUND: Diarrhea is commonly associated with irritable bowel syndrome, inflammatory bowel disease, microscopic colitis, and other gastrointestinal dysfunctions. Spontaneously occurring idiopathic chronic diarrhea is frequent in rhesus macaques, but has not been used as a model for the investigation of diarrhea or its treatment. We characterized this condition and present preliminary data demonstrating that left vagal nerve stimulation provides relief. METHODS: Stool consistency scores were followed for up to 12 years. Inflammation was assessed by plasma C-reactive protein, [18F]fluorodeoxyglucose (FDG) uptake, measured by positron emission tomography (PET), multiplex T cell localization, endoscopy and histology. The vagus was stimulated for 9 weeks in conscious macaques, using fully implanted electrodes, under wireless control. KEY RESULTS: Macaques exhibited recurrent periods of diarrhea for up to 12 years, and signs of inflammation: elevated plasma C-reactive protein, increased bowel FDG uptake and increased mucosal T helper1 T-cells. The colon and distal ileum were endoscopically normal, and histology revealed mild colonic inflammation. Application of vagal nerve stimulation to conscious macaques (10 Hz, 30 s every 3 h; 24 h a day for 9 weeks) significantly reduced severity of diarrhea and also reduced inflammation, as measured by FDG uptake and C-reactive protein. CONCLUSIONS AND INFERENCES: These macaques exhibit spontaneously occurring diarrhea with intestinal inflammation that can be reduced by VNS. The data demonstrate the utility of this naturally occurring primate model to study the physiology and treatments for chronic diarrhea and the neural control circuits influencing diarrhea and inflammation that are not accessible in human subjects.

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In the realm of gastroenterology, the inadequacy of current medical treatments for gastrointestinal (GI) motility disorders and inflammatory bowel disease (IBD), coupled with their potential side effects, necessitates novel therapeutic approaches. Neuromodulation, targeting the nervous system's control of GI functions, emerges as a promising alternative. This review explores the promising effects of vagal nerve stimulation (VNS), magnetic neuromodulation, and acupuncture in managing these challenging conditions. VNS offers targeted modulation of GI motility and inflammation, presenting a potential solution for patients not fully relieved from traditional medications. Magnetic neuromodulation, through non-invasive means, aims to enhance neurophysiological processes, showing promise in improving GI function and reducing inflammation. Acupuncture and electroacupuncture, grounded in traditional medicine yet validated by modern science, exert comprehensive effects on GI physiology via neuro-immune-endocrine mechanisms, offering relief from motility and inflammatory symptoms. This review highlights the need for further research to refine these interventions, emphasizing their prospective role in advancing patient-specific management strategies for GI motility disorders and IBD, thus paving the way for a new therapeutic paradigm.

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Heart rate variability (HRV) analysis provides an assessment of cardiac vagal tone and consequently global cardiac health as well as systemic condition. In systemic diseases such as cancer and during treatments that affect the whole body, like chemotherapy, the vagus nerve activity is low and deregulated. Some studies focus on using HRV to predict mortality in oncology. However, in cancer patients, systemic alterations substantially increase artifacts during HRV measurement, especially atrial ectopic beats. Moreover, HRV may be altered by various factors (duration and time of measurement, breathing, drugs, and other confounding factors) that alter each metric in different ways. The Standard Deviation of all Normal to Normal intervals (SDNN) is the most commonly used metric to evaluate HRV in oncology, but it does not appear to be specific to the cardiac vagal tone. Thus, cardiac vagal activity diagnosis and vital prognosis of cancer patients can be biased. Our review presents the main HRV metrics that can be currently used in oncology studies and their links with vagus nerve and cancer. We present the influence of external factors and the required duration and time of measurement. Considering all these parameters, this review proposes seven key points for an assessment of HRV and cardiac vagal tone in patients with cancer.

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BACKGROUND: Recent evidence demonstrates that manually triggered vagus nerve stimulation (VNS) combined with rehabilitation leads to increased recovery of upper limb motor function after stroke. This approach is premised on studies demonstrating that the timing of stimulation relative to movements is a key determinant in the effectiveness of this approach. OBJECTIVE: The overall goal of the study was to identify an algorithm that could be used to automatically trigger VNS on the best movements during rehabilitative exercises while maintaining a desired interval between stimulations to reduce the burden of manual stimulation triggering. METHODS: To develop the algorithm, we analyzed movement data collected from patients with a history of neurological injury. We applied 3 different algorithms to the signal, analyzed their triggering choices, and then validated the best algorithm by comparing triggering choices to those selected by a therapist delivering VNS therapy. RESULTS: The dynamic algorithm triggered above the 95th percentile of maximum movement at a rate of 5.09 (interquartile range [IQR] = 0.74) triggers per minute. The periodic algorithm produces stimulation at set intervals but low movement selectivity (34.05%, IQR = 7.47), while the static threshold algorithm produces long interstimulus intervals (27.16 ± 2.01 seconds) with selectivity of 64.49% (IQR = 25.38). On average, the dynamic algorithm selects movements that are 54 ± 3% larger than therapist-selected movements. CONCLUSIONS: This study shows that a dynamic algorithm is an effective strategy to trigger VNS during the best movements at a reliable triggering rate.

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Hypertension-related diseases occur in both hypertensive and non-hypertensive individuals. However, few studies to date have explored blood pressure (BP) control in non-hypertensive individuals. This before-after study aimed to examine the impact of visual stimulation-based digital therapeutics (VS-DTx) on BP and heart rate (HR). Eighty-three eligible non-hypertensive participants were included in this study. The McNemar test and Paired Samples Wilcoxon Signed Rank Test were employed to assess decline rates and differences in BP and HR between the control phase and the intervention (using VS-DTx) phase. Pairwise correlation analysis was used to analyze the correlation between the two phases. This study found the systolic BP (SBP) and mean arterial pressure (MAP) in the VS-DTx phase showed a downward trend (66.2% vs 49.3%; 68.7% vs 55.4%). The mean SBP decreased from 114.73 mm Hg to 111.18 mm Hg, and the mean MAP decreased from 87.96 mm Hg to 84.88 mm Hg in the VS-DTx phase. Paired Samples Wilcoxon Test showed differences in both ΔSBP (Z = -3.296; P < 0.01) and ΔMAP (Z = -2.386; P < 0.05) (Δ is defined as the difference between baseline and post-stimulus). The pairwise correlations analysis revealed that VS-DTx affected the MAP reduction (r = 0.33; P < 0.01) between the browsing digital devices phase and the VS-DTx phase. The results indicated that VS-DTx may have a certain effect on BP, including SBP and MAP. This study preliminarily explored the possible effects of VS-DTx on BP, providing certain useful insights for future research in digital BP management.

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Stimulation of the inflammatory reflex (IR) is a promising strategy for treating systemic inflammatory disorders. Recent studies suggest oral sodium bicarbonate (NaHCO3) as a potential activator of the IR, offering a safe and cost-effective treatment approach. However, the mechanisms underlying NaHCO3-induced anti-inflammatory effects remain unclear. We investigated whether oral NaHCO3's immunomodulatory effects are mediated by the splenic nerve. Female rats received NaHCO3 or water (H2O) for four days, and splenic immune markers were assessed using flow cytometry. NaHCO3 led to a significant increase (p < 0.05, and/or partial eta squared > 0.06) in anti-inflammatory markers, including CD11bc + CD206 + (M2-like) macrophages, CD3 + CD4 + FoxP3 + cells (Tregs), and Tregs/M1-like ratio. Conversely, proinflammatory markers, such as CD11bc + CD38 + TNFα + (M1-like) macrophages, M1-like/M2-like ratio, and SSChigh/SSClow ratio of FSChighCD11bc + cells, decreased in the spleen following NaHCO3 administration. These effects were abolished in spleen-denervated rats, suggesting the necessity of the splenic nerve in mediating NaHCO3-induced immunomodulation. Artificial neural networks accurately classified NaHCO3 and H2O treatment in sham rats but failed in spleen-denervated rats, highlighting the splenic nerve's critical role. Additionally, spleen denervation independently influenced Tregs, M2-like macrophages, Tregs/M1-like ratio, and CD11bc + CD38 + cells, indicating distinct effects from both surgery and treatment. Principal component analysis (PCA) further supported the separate effects. Our findings suggest that the splenic nerve transmits oral NaHCO3-induced immunomodulatory changes to the spleen, emphasizing NaHCO3's potential as an IR activator with therapeutic implications for a wide spectrum of systemic inflammatory conditions.

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BACKGROUND: Excessive fear, worry and behavioral disturbances define anxiety, with particular significance attributed to vagal nerve, a crucial transmitter of information to the brain regions governing anxiety. Highlighting the importance of vagal nerve, transcutaneous auricular vagal nerve stimulation (TaVNS) emerges as a tolerable and safe technique. The success of non-invasive vagal nerve stimulation in alleviating anxiety underscores the pivotal role of the vagal nerve. OBJECTIVES: The purpose of this study was to assess the effectiveness of physiotherapy interventions in mitigating anxiety among retired teachers during the COVID-19 pandemic, emphasizing the relevance of targeting the vagal nerve for improved mental well-being. METHODS: 60 retired teachers diagnosed with anxiety were chosen through random allocation. Participants were divided into two groups: Group A (Experimental group) received transcutaneous auricular vagal nerve stimulation (TaVNS), and Group B (Control group) underwent the Jacobson relaxation technique. Intervention period spanned 4 weeks, with four sessions per week, lasting 30 minutes. The outcome measures included Generalized Anxiety Disorder-7 (GAD-7) questionnaire and salivary cortisol levels. RESULTS: Following the 4-week intervention, both groups exhibited a significant reduction in Generalized Anxiety Disorder-7 (GAD-7) scores and salivary cortisol levels (P <  0.001). Notably, Group A demonstrated a significantly higher effectiveness rate compared to Group B. CONCLUSION: The study concludes that transcutaneous auricular vagal nerve stimulation (TaVNS) is effective in reducing anxiety among retired teachers. Transcutaneous auricular vagal nerve stimulation (TaVNS) proves to be a powerful and effective intervention in alleviating anxiety among retired teachers, emphasizing its potential significance in enhancing mental well-being.

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AIMS/HYPOTHESIS: Diabetic gastroenteropathy frequently causes debilitating gastrointestinal symptoms. Previous uncontrolled studies have shown that transcutaneous vagal nerve stimulation (tVNS) may improve gastrointestinal symptoms. To investigate the effect of cervical tVNS in individuals with diabetes suffering from autonomic neuropathy and gastrointestinal symptoms, we conducted a randomised, sham-controlled, double-blind (participants and investigators were blinded to the allocated treatment) study. METHODS: This study included adults (aged 20-86) with type 1 or 2 diabetes, gastrointestinal symptoms and autonomic neuropathy recruited from three Steno Diabetes Centres in Denmark. Participants were randomly allocated 1:1 to receive active or sham stimulation. Active cervical tVNS or sham stimulation was self-administered over two successive study periods: 1 week of four daily stimulations and 8 weeks of two daily stimulations. The primary outcome measures were gastrointestinal symptom changes as measured using the gastroparesis cardinal symptom index (GCSI) and the gastrointestinal symptom rating scale (GSRS). Secondary outcomes included gastrointestinal transit times and cardiovascular autonomic function. RESULTS: Sixty-eight participants were randomised to the active group, while 77 were randomised to the sham group. Sixty-three in the active and 68 in the sham group remained for analysis in study period 1, while 62 in each group were analysed in study period 2. In study period 1, active and sham tVNS resulted in similar symptom reductions (GCSI: -0.26 ± 0.64 vs -0.17 ± 0.62, p=0.44; GSRS: -0.35 ± 0.62 vs -0.32 ± 0.59, p=0.77; mean ± SD). In study period 2, active stimulation also caused a mean symptom decrease that was comparable to that observed after sham stimulation (GCSI: -0.47 ± 0.78 vs -0.33 ± 0.75, p=0.34; GSRS: -0.46 ± 0.90 vs -0.35 ± 0.79, p=0.50). Gastric emptying time was increased in the active group compared with sham (23 min vs -19 min, p=0.04). Segmental intestinal transit times and cardiovascular autonomic measurements did not differ between treatment groups (all p>0.05). The tVNS was well-tolerated. CONCLUSIONS/INTERPRETATION: Cervical tVNS, compared with sham stimulation, does not improve gastrointestinal symptoms among individuals with diabetes and autonomic neuropathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT04143269 FUNDING: The study was funded by the Novo Nordisk Foundation (grant number NNF180C0052045).

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Vagal nerve stimulation (VNS) provides a novel therapeutic strategy for injured hearts by activating cholinergic anti-inflammatory pathways. However, little information is available on the metabolic pattern and arteriogenesis of VSMCs after MI. VNS has been shown to stimulate the expression of CPT1α, CPT1ß, Glut1, Glut4 and SDF-1α in coronary VSMCs, decreasing the number of CD68-positive macrophages while increasing CD206-positive macrophages in the infarcted hearts, leading to a decrease in TNF-α and IL-1ß accompanied by a reduced ratio of CD68- and CD206-positive cells, which were dramatically abolished by atropine and mecamylamine in vivo. Knockdown of SDF-1α substantially abrogated the effect of VNS on macrophagecell alteration and inflammatory factors in infarcted hearts. Mechanistically, ACh induced SDF-1α expression in VSMCs in a dose-dependent manner. Conversely, atropine, mecamylamine, and a PI3K/Akt inhibitor completely eliminated the effect of ACh on SDF-1α expression. Functionally, VNS promoted arteriogenesis and improved left ventricular performance, which could be abolished by Ad-shSDF-1α. Thus, VNS altered the VSMC metabolism pattern and arteriogenesis to repair the infarcted heart by inducing SDF-1α expression, which was associated with the m/nAChR-Akt signaling pathway.

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PURPOSE: To evaluate the quality of available information on Youtube videos about VNS as a "source of health information" for patients with drug resistant epilepsy. METHODS: Youtube videos were searched and screened using the terms "VNS for seizures," and "VNS surgery," "VNS epilepsy" in May 2023. The quality of the videos was evaluated the Quality Criteria for Consumer Health Information (DISCERN) and Global Quality Scale (GQS). The videos were analyzed in terms of content, accuracy, reliability, and quality. RESULTS: A total of 104 videos were searched. After excluding duplicate or inappropriate videos, 51 videos were analyzed. Youtube videos about vagal nerve stimulation are mostly on general information, surgical procedures, patient experiences and magnet use. When video sources are examined according to the quality, according to GQS, 75 % of high quality videos were narrated by physicians, all intermediate quality videos were narrated by physicians, and low quality ones narrated by physicians were 47.4 % and 28.9 % by the patients. All of the videos narrated by the patients were of low quality. There was a significant and strong correlation between GQS and Discern score (r = 0.807, p < 0.001). Only GQS scores of videos with different content were found to be statistically significant (p < 0.05). Two pediatric neurologists independently reviewed the videos and classified the videos as useful or misleading according to the GQS, DISCERN scala. The overall κ value for interobserver consistency according to Global Quality Scale was 0.781 (p < 0.001). (95 % confidence interval), indicating a very good level of agreement. CONCLUSION: Youtube videos may provide a worthful source for patients and parents seeking to find more information about VNS However incorrect information could easily be disseminated by high number of views of videos with low quality. High skilled and experienced professionals should create videos on Youtube to ensure that patients and parents can access more useful, high-quality, and accurate information on VNS.

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Angelman syndrome (AS) is a rare neurodevelopmental disorder that is typically caused by deletion or a loss-of-function mutation of the maternal copy of the ubiquitin ligase E3A (UBE3A) gene. The disorder is characterized by severe intellectual disability, deficits in speech, motor abnormalities, altered electroencephalography (EEG) activity, spontaneous epileptic seizures, sleep disturbances, and a happy demeanor with frequent laughter. Regarding electrophysiologic abnormalities in particular, enhanced delta oscillatory power and an elevated excitatory/inhibitory (E/I) ratio have been documented in AS, with E/I ratio especially studied in rodent models. These electrophysiologic characteristics appear to relate with the greatly elevated rates of epilepsy in individuals with AS, and associated hypersynchronous neural activity. Here we briefly review findings on EEG, E/I ratio, and epileptic seizures in AS, including data from rodent models of the disorder. We summarize pharmacologic approaches that have been used to treat behavioral aspects of AS, including neuropsychiatric phenomena and sleep disturbances, as well as seizures in the context of the disorder. Antidepressants such as SSRIs and atypical antipsychotics are among the medications that have been used behaviorally, whereas anticonvulsant drugs such as valproic acid and lamotrigine have frequently been used to control seizures in AS. We end by suggesting novel uses for some existing pharmacologic agents in AS, including noradrenergic transmission reducing drugs (alpha2 agonists, beta blockers, alpha1 antagonists) and cholinesterase inhibitors, where these various classes of drugs may have the ability to ameliorate both behavioral disturbances and seizures.

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INTRODUCTION: Obesity affects millions of Americans. The vagal nerves convey the degree of stomach fullness to the brain via afferent visceral fibers. Studies have found that vagal nerve stimulation (VNS) promotes reduced food intake, causes weight loss, and reduces cravings and appetite. METHODS: Here, we evaluate the efficacy of a novel stimulus waveform applied bilaterally to the subdiaphragmatic vagal nerve stimulation (sVNS) for almost 13 weeks. A stimulating cuff electrode was implanted in obesity-prone Sprague Dawley rats maintained on a high-fat diet. Body weight, food consumption, and daily movement were tracked over time and compared against three control groups: sham rats on a high-fat diet that were implanted with non-operational cuffs, rats on a high-fat diet that were not implanted, and rats on a standard diet that were not implanted. RESULTS: Results showed that rats on a high-fat diet that received sVNS attained a similar weight to rats on a standard diet due primarily to a reduction in daily caloric intake. Rats on a high-fat diet that received sVNS had significantly less body fat than other high-fat controls. Rats receiving sVNS also began moving a similar amount to rats on the standard diet. CONCLUSION: Results from this study suggest that bilateral subdiaphragmatic vagal nerve stimulation can alter the rate of growth of rats maintained on a high-fat diet through a reduction in daily caloric intake, returning their body weight to that which is similar to rats on a standard diet over approximately 13 weeks.

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OBJECTIVE: Functional dyspepsia (FD), which has a complicated pathophysiologic process, is a common functional gastrointestinal disease. Gastric hypersensitivity is the key pathophysiological factor in patients with FD with chronic visceral pain. Auricular vagal nerve stimulation (AVNS) has the therapeutic effect of reducing gastric hypersensitivity by regulating the activity of the vagus nerve. However, the potential molecular mechanism is still unclear. Therefore, we investigated the effects of AVNS on the brain-gut axis through the central nerve growth factor (NGF)/ tropomyosin receptor kinase A (TrkA)/phospholipase C-gamma (PLC-γ) signaling pathway in FD model rats with gastric hypersensitivity. MATERIALS AND METHODS: We established the FD model rats with gastric hypersensitivity by means of colon administration of trinitrobenzenesulfonic acid on ten-day-old rat pups, whereas the control rats were given normal saline. AVNS, sham AVNS, K252a (an inhibitor of TrkA, intraperitoneally), and K252a + AVNS were performed on eight-week-old model rats for five consecutive days. The therapeutic effect of AVNS on gastric hypersensitivity was determined by the measurement of abdominal withdrawal reflex response to gastric distention. NGF in gastric fundus and NGF, TrkA, PLC-γ, and transient receptor potential vanilloid 1 (TRPV1) in the nucleus tractus solitaries (NTS) were detected separately by polymerase chain reaction, Western blot, and immunofluorescence tests. RESULTS: It was found that a high level of NGF in gastric fundus and an upregulation of the NGF/TrkA/PLC-γ signaling pathway in NTS were manifested in model rats. Meanwhile, both AVNS treatment and the administration of K252a not only decreased NGF messenger ribonucleic acid (mRNA) and protein expressions in gastric fundus but also reduced the mRNA expressions of NGF, TrkA, PLC-γ, and TRPV1 and inhibited the protein levels and hyperactive phosphorylation of TrkA/PLC-γ in NTS. In addition, the expressions of NGF and TrkA proteins in NTS were decreased significantly after the immunofluorescence assay. The K252a + AVNS treatment exerted a more sensitive effect on regulating the molecular expressions of the signal pathway than did the K252a treatment. CONCLUSION: AVNS can regulate the brain-gut axis effectively through the central NGF/TrkA/PLC-γ signaling pathway in the NTS, which suggests a potential molecular mechanism of AVNS in ameliorating visceral hypersensitivity in FD model rats.

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Background: Transcutaneous auricular vagus nerve stimulation (taVNS) emerges as a promising neuromodulatory technique. However, taVNS uses left ear stimulation in stroke survivors with either left or right hemiparesis. Understanding its influence on the cortical responses is pivotal for optimizing post-stroke rehabilitation protocols. Objective: The primary objective of this study was to elucidate the influence of taVNS on cortical responses in stroke patients presenting with either left or right hemiparesis and to discern its potential ramifications for upper limb rehabilitative processes. Methods: We employed functional near-infrared spectroscopy (fNIRS) to ascertain patterns of cerebral activation in stroke patients as they engaged in a "block transfer" task. Additionally, the Lateralization Index (LI) was utilized to quantify the lateralization dynamics of cerebral functions. Results: In patients exhibiting left-side hemiplegia, there was a notable increase in activation within the pre-motor and supplementary motor cortex (PMC-SMC) of the unaffected hemisphere as well as in the left Broca area. Conversely, those with right-side hemiplegia displayed heightened activation in the affected primary somatosensory cortex (PSC) region following treatment.Significantly, taVNS markedly amplified cerebral activation, with a pronounced impact on the left motor cortical network across both cohorts. Intriguingly, the LI showcased consistency, suggesting a harmonized enhancement across both compromised and uncompromised cerebral regions. Conclusion: TaVNS can significantly bolster the activation within compromised cerebral territories, particularly within the left motor cortical domain, without destabilizing cerebral lateralization. TaVNS could play a pivotal role in enhancing upper limb functional restoration post-stroke through precise neuromodulatory and neuroplastic interventions.

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Surgically implanted neurostimulation devices for the treatment of depression have been studied for the last three decades. While the surgical risk associated with these treatment approaches clearly limits their use to the most severely impacted depressed patients, they offer a unique opportunity to better understand the impact of relatively localized alteration of neural activity in patient groups. As a result, these approaches provide a strict test of the role of individual neural structures or networks in mechanistic models of depression. In this chapter, we review the proposed mechanisms of action and evidence for clinical efficacy of vagal nerve stimulation, deep brain stimulation, and epidural cortical stimulation in patients with depression. The evidence for efficacy remains limited for all three modalities, but the long-term follow-up studies of treated patients have highlighted the importance of interactions between neural regions in determining therapeutic response, and suggest that personalized approaches to stimulation are likely to be required.

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In this study, it was aimed to investigate the effects of switching off stimulation on time perception in patients with drug-resistant epilepsy who underwent Vagal Nerve Stimulation (VNS). In accordance with the literature, a cognitive battery of tests for motor timing and perceptual timing was utilized. Computerized time perception tests; Paced Motor Timing Test, Duration Discrimination Test, Temporal Reproduction Test, and Time Estimation Test were administered to the patients while VNS was on and off. A total of 14 patients who met the inclusion criteria of 23 VNS patients followed in the Epilepsy Outpatient Clinic were included in the study. In the Temporal Reproduction Test, for time durations of 1000 ms (ms), 2000 ms, 3000 ms, 4000 ms, and 5000 ms the comparison of reported time values between VNS on and VNS off yielded respective p values; p = 0.73, p = 0.03, p = 0.176, p = 0.418, p = 0,873. The reported time is thus significantly shorter only for 2000 ms when the VNS was on. Positive effect of VNS on attention, alertness and focusing are expected to cause acceleration of the internal clock resulting in perceiving time running slower than actual. In our study, it was concluded that the internal clock runs faster when the VNS is on, and time is perceived as running slower than it actually is. This result can also be accepted as an indirect indicator of increased attention in the period when VNS is on.

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