Effects Of Vagus Nerve Stimulation Research Articles

Effect of vagus nerve stimulation against generalized seizure and status epilepticus recurrence.

Vagus nerve stimulation (VNS) is a palliative surgery for drug-resistant epilepsy. The two objectives of this study were to (1) determine the seizure type most responsive to VNS and (2) investigate the preventive effect on status epilepticus (SE) recurrence. We retrospectively reviewed 136 patients with drug-resistant epilepsy who underwent VNS implantation. We examined seizure outcomes at 6, 12, and 24 months following implantation of VNS as well as at the last visit to the Juntendo Epilepsy Center. Univariate analysis and multivariate logistic regression models were used to estimate the prognostic factors. 125 patients were followed up for at least 1 year after VNS implantation. The percentage of patients with at least a 50% reduction in seizure frequency compared with prior to VNS implantation increased over time at 6, 12, and 24 months after VNS implantation: 28, 41, and 52%, respectively. Regarding overall seizure outcomes, 70 (56%) patients responded to VNS. Of the 40 patients with a history of SE prior to VNS implantation, 27 (67%) showed no recurrence of SE. The duration of epilepsy, history of SE prior to VNS implantation and seizure type were correlated with seizure outcomes after VNS implantation in univariate analysis (p = 0.05, p < 0.01, and p = 0.03, respectively). In multivariate logistic regression analysis, generalized seizure was associated with VNS response [odds ratio (OR): 4.18, 95% CI: 1.13-15.5, p = 0.03]. A history of SE prior to VNS implantation was associated with VNS non-responders [(OR): 0.221, 95% CI: 0.097-0.503, p < 0.01]. The duration of epilepsy, focal to bilateral tonic-clonic seizure and epileptic spasms were not significantly associated with VNS responders (p = 0.07, p = 0.71, and p = 0.11, respectively). Following 125 patients with drug-resistant epilepsy for an average of 69 months, 56% showed at least 50% reduction in seizure frequency after VNS implantation. This study suggests that generalized seizure is the most responsive to VNS, and that VNS may reduce the risk of recurrence of SE. VNS was shown to be effective against generalized seizure and also may potentially influence the risk of further events of SE, two marker of disease treatment that can lead to improved quality of life.

Frequency-specific modulation of oscillatory activity in the rat auditory cortex by vagus nerve stimulation

BackgroundWe previously found that vagus nerve stimulation (VNS) strengthened stimulus-evoked activity in the superficial layer of the sensory cortex but not in the deep layer, suggesting that VNS altered the balance between the feedforward (FF) and feedback (FB) pathways. Band-specific oscillatory activities in the cortex could serve as an index of the FF-FB balance, but whether VNS affects cortical oscillations along sensory pathways through neuromodulators remains unclear. HypothesisVNS modulates the FF-FB balance through the cholinergic and noradrenergic systems, which modulate stimulus gain in the cortex. MethodsWe investigated the effects of VNS using electrocorticography in the auditory cortex of 34 Wistar rats under general anesthesia while presenting click stimuli. In the time-frequency analyses, the putative modulation of the FF and FB pathways was estimated using high- and low-frequency power. We assessed, using analysis of variance, how VNS modulates auditory-evoked activities and how the modulation changes with cholinergic and noradrenergic antagonists. ResultsVNS increased auditory cortical evoked potentials, consistent with results of our previous work. Furthermore, VNS increased auditory-evoked gamma and beta powers and decreased theta power. Local administration of cholinergic antagonists in the auditory cortex selectively disrupted the VNS-induced increase in gamma and beta power, while noradrenergic antagonists disrupted the decrease in theta power. ConclusionsVNS might strengthen the FF pathway through the cholinergic system and attenuate the FB pathway through the noradrenergic system in the auditory cortex. Cortical gain modulation through the VNS-induced neuromodulatory system provides new mechanistic insights into the effect of VNS on auditory processing.

Vagus Nerves Stimulation: Clinical Implication and Practical Issue as a Neuropsychiatric Treatment.

Vagus nerve stimulation (VNS) has been approved as an adjunctive treatment for epilepsy and depression. As the progress of VNS treatment for these neuropsychiatric disorders continues, its applications have expanded to a wide range of conditions, including inflammatory diseases to cognitive dysfunctions. The branches of the vagal nerves directly or indirectly innervate the anatomical structures implicated in these neuropsychiatric conditions, which has led to promising results regarding the effectiveness of VNS. Previous studies investigating the effectiveness of VNS have mostly utilized invasive forms of stimulation. However, current preclinical and clinical research indicates that non-invasive forms of VNS, such as transcutaneous vagus nerve stimulation, hold the promise for treating various neuropsychiatric conditions. This review aims to delve into relevant clinical studies of VNS in various illness states, different methods of VNS, and the potential mechanisms underlying the therapeutic effects in these neuropsychiatric conditions.

Vagal electrostimulation in postoperative thoracic surgery reduces the systemic inflammatory response and cardiopulmonary complications: an experimental study in pigs.

Conventional thoracotomy (CT) often leads to systemic inflammatory response syndrome (SIRS), which induces several clinical complications. CT remains widely used in low-income institutions. Although minimally invasive surgical procedures, such as robotic surgery (RS), have been used to prevent many of the complications inherit from the surgical procedure. Here, we investigated the protective effect of vagus nerve stimulation (VNS) in a pre-clinical model during CT or RS and postoperative period (POP) relative to clinical complications and inflammatory control. The objective was to compare hemodynamic features and cytokine levels in the blood, lung, and bronchoalveolar lavage (BAL) fluids of animals subjected to CT or RS with or without VNS. Twenty-four minipigs were subjected to 12 animals CT and 12 animals RS, with or without VNS, and accompanied 24 h later by pulmonary lobectomy. Blood samples for evaluating the hemodynamic parameters were collected before the surgical preparation, immediately after the beginning of VNS, and every 4 h until 24 h after the lobectomy. BAL fluid and lung tissue were collected at the end of the experiment. Cytokine levels were evaluated in the blood, BAL fluid, and lung tissues. VNS maintained a more stable heart rate during POP and decreased the incidence of overall cardiac complications while preventing increase in IL-6 levels 12 h after lobectomy, compared to sham animals. No differences were found in cytokine expression in the BAL fluid and lung tissue in any of the studied groups. Taken together, our data suggested that VNS should be considered a non-pharmacological tool in the prevention of the exacerbated inflammatory response responsible for severe clinical complications, especially in more aggressive surgical procedures.

Ultrasound stimulation of the vagal nerve improves acute septic encephalopathy in mice.

Septic encephalopathy (SE) is characterized by symptoms such as coma, delirium, and cognitive dysfunction, and effective therapeutic interventions for SE remain elusive. In this study, we aimed to investigate the potential alleviating effects of vagal nerve stimulation (VNS) on SE-associated signs. To evaluate our hypothesis, we utilized a mouse model of SE induced by intraperitoneal injection of lipopolysaccharide (0.3 mg per mouse) and administered noninvasive, high-frequency ultrasound VNS. To assess the efficacy of ultrasound VNS, we measured inflammation-related molecules, including the α7 nicotinic acetylcholine receptor (α7nAChR) expression in peritoneal macrophages and plasma interleukin 1β (IL-1β) levels. Consistent with our hypothesis, SE mice exhibited reduced α7nAChR expression in macrophages and elevated IL-1β levels in the blood. Remarkably, VNS in SE mice restored α7nAChR expression and IL-1β levels to those observed in control mice. Furthermore, we evaluated the effects of VNS on survival rate, body temperature, and locomotor activity. SE mice subjected to VNS demonstrated a modest, yet significant, improvement in survival rate, recovery from hypothermia, and increased locomotor activity. To investigate the impact on the brain, we examined the hippocampus of SE mice. In control mice, VNS increased the expression of c-fos, a marker of neuronal electrical excitability, in the hippocampus. In SE mice, VNS led to the restoration of aberrant firing patterns in hippocampal neurons. Additionally, proteomic analysis of hippocampal tissue in SE mice revealed abnormal increases in two proteins, tissue factor (TF) and acyl-CoA dehydrogenase family member 9 (ACAD9), which returned to control levels following VNS. Collectively, our findings support the value of exploring the beneficial effects of ultrasound VNS on SE.

Effect of transcutaneous cervical vagus nerve stimulation on declarative and working memory in patients with Posttraumatic Stress Disorder (PTSD): A pilot study

BackgroundPosttraumatic stress disorder (PTSD) is associated with changes in multiple neurophysiological systems, including verbal declarative memory deficits. Vagus Nerve Stimulation (VNS) has been shown in preliminary studies to enhance function when paired with cognitive and motor tasks. The purpose of this study was to analyze the effect of transcutaneous cervical VNS (tcVNS) on attention, declarative and working memory in PTSD patients. MethodsFifteen PTSD patients were randomly assigned to active tcVNS (N = 8) or sham (N = 7) stimulation in a double-blinded fashion. Memory assessment tests including paragraph recall and N-back tests were performed to assess declarative and working memory function when paired with active/sham tcVNS once per month in a longitudinal study during which patients self-administered tcVNS/sham twice daily. ResultsActive tcVNS stimulation resulted in a significant improvement in paragraph recall performance following pairing with paragraph encoding for PTSD patients at two months (p < 0.05). It resulted in a 91 % increase in paragraph recall performance within group (p = 0.03), while sham tcVNS exhibited no such trend in performance improvement. In the N-back study, positive deviations in accuracy, precision and recall measures on different day visits (7,34,64,94) of patients with respect to day 1 revealed a pattern of better performance of the active tcVNS population compared to sham VNS which did not reach statistical significance. LimitationsOur sample size was small. ConclusionsThese preliminary results suggest that tcVNS improves attention, declarative and working memory, which may improve quality of life and productivity for patients with PTSD. Future studies are required to confirm these results.

Neuroimmunomodulation of vagus nerve stimulation and the therapeutic implications.

Vagus nerve stimulation (VNS) is a technology that provides electrical stimulation to the cervical vagus nerve and can be applied in the treatment of a wide variety of neuropsychiatric and systemic diseases. VNS exerts its effect by stimulating vagal afferent and efferent fibers, which project upward to the brainstem nuclei and the relayed circuits and downward to the internal organs to influence the autonomic, neuroendocrine, and neuroimmunology systems. The neuroimmunomodulation effect of VNS is mediated through the cholinergic anti-inflammatory pathway that regulates immune cells and decreases pro-inflammatory cytokines. Traditional and non-invasive VNS have Food and Drug Administration (FDA)-approved indications for patients with drug-refractory epilepsy, treatment-refractory major depressive disorders, and headaches. The number of clinical trials and translational studies that explore the therapeutic potentials and mechanisms of VNS is increasing. In this review, we first introduced the anatomical and physiological bases of the vagus nerve and the immunomodulating functions of VNS. We covered studies that investigated the mechanisms of VNS and its therapeutic implications for a spectrum of brain disorders and systemic diseases in the context of neuroimmunomodulation.

Left or right ear? A neuroimaging study using combined taVNS/fMRI to understand the interaction between ear stimulation target and lesion location in chronic stroke

BackgroundImplanted vagus nerve stimulation (VNS) and transcutaneous auricular VNS (taVNS) have been primarily administered clinically to the unilateral-left vagus nerve. This left-only convention has proved clinically beneficial in brain disorders. However, in stroke survivors, the presence of a lesion in the brain may complicate VNS-mediated signaling, and it is important to understand the laterality effects of VNS in stroke survivors to optimize the intervention. ObjectiveTo understand whether taVNS delivered to different ear targets relative to the lesion (ipsilesional vs contralesional vs bilateral vs sham) impacts blood oxygenation level dependent (BOLD) signal propagation in stroke survivors. MethodsWe enrolled 20 adults with a prior history of stroke. Each participant underwent a single visit, during which taVNS was delivered concurrently during functional magnetic resonance imaging (fMRI) acquisition. Each participant received three discrete active stimulation conditions (ipsilesional, contralesional, bilateral) and one sham condition in a randomized order. Stimulation-related BOLD signal changes in the active conditions were compared to sham conditions to understand the interaction taVNS and laterality effects. ResultsAll active taVNS conditions deactivated the contralesional default mode network related regions compared to sham, however only ipsilesional taVNS enhanced the activations in the ipsilesional visuomotor and secondary visual cortex. Furthermore, we reveal an interaction in task activations between taVNS and cortical visuomotor areas, where ipsilesional taVNS significantly increased ipsilesional visuomotor activity and decreased contralesional visuomotor activity compared to sham. ConclusionLaterality of taVNS relative to the lesion is a critical factor in optimizing taVNS in a stroke population, with ipsilesional stimulation providing largest direct brain activation and should be explored further when designing taVNS studies in neurorehabilitation.

Vagus Nerve Stimulation Through Electro-acupuncture for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is defined as a chronic inflammatory-mediated disease that causes ulceration and inflammation in the gastrointestinal tract. Among most patients, the course of chronic inflammation repeatedly shows intermittent exacerbations and alternating remissions. However, despite the various therapeutic options to relieve symptoms, such as corticosteroids, TNF-α inhibitors, and antibiotic drugs, there is no known cure for IBD. Nonetheless, previous research has revealed that the autonomic nervous system is involved in the pathophysiology of IBD. In this study, we reviewed clinical trials confirming the therapeutic effect of vagus nerve stimulation (VNS) on IBD in vivo. We searched in vivo and human studies on Pubmed using keywords combined with “vagus nerve stimulation”, “VNS”, and “inflammatory bowel disease”. All studies included in this review reported that direct VNS is effective in relieving symptoms of IBD and has no severe adverse effects. The most frequently stimulated site was the unilateral cervical vagus nerve area, and parameters for stimulation were set as 5-20 Hz. Based on the results, we aim to summarize the evidence for the efficacy of VNS on IBD and suggest the possibility of auricular electroacupuncture treatment as a therapeutic option for IBD.

Does response to vagus nerve stimulation for drug-resistant epilepsy differ in patients with and without Lennox-Gastaut syndrome?

Literature on outcomes of patients with Lennox-Gastaut syndrome (LGS) receiving adjunctive vagus nerve stimulation (VNS) lacks information on seizure types and the time course of therapeutic effects. We have therefore performed what is to our knowledge the largest and most in-depth analysis of the effectiveness of VNS in LGS patients paying special attention to the impact of VNS Therapy on individual seizure types. The VNS Therapy Outcomes Registry includes over 7000 patients. A propensity score matching method was employed to match patients with LGS to non-LGS patients with drug-resistant epilepsy (DRE). Overall seizure frequencies were assessed prior to implantation and at 3-, 6-, 12-, 18-, and 24-month follow-ups to derive the main study outcomes: response rates and time to first response. A total of 564 LGS patients with sufficient data were identified in the registry and matched 2:1 to 1128 non-LGS patients. Responder rates at 24 months were 57.5% in the LGS group and 61.5% in the non-LGS group. Median seizure frequency reduction at 24 months was 64.3% versus 66.7% in the LGS versus non-LGS group, respectively. In both groups, VNS was most effective at reducing focal aware seizures, "other" seizures, generalized-onset non-motor seizures, and drop attacks with relative reduction rates for these seizure types at 24 months exceeding 90% in both groups. Time-to-first response did not differ between the groups; however, there was a significantly higher proportion of patients who regressed from bilateral tonic-clonic (BTC) seizure response in the LGS group versus the non-LGS group at 24 months: 22.4% versus 6.7%; p=.015. Although limited by its retrospective design, the study shows that the effectiveness of VNS is comparable in DRE patients with and without LGS; however, LGS patients may be more prone to fluctuating control of BTCs.

Synergistic effects of vagus nerve stimulation and antiseizure medication

IntroductionVagus nerve stimulation (VNS) is an effective, non-pharmacological therapy for epileptic seizures. Until now, favorable combinations of different groups of antiseizure medication (ASM) and VNS have not been sufficiently addressed. The aim of this study was to identify the synergistic effects between VNS and different ASMs.MethodsWe performed an observational study of patients with epilepsy who were implanted with VNS and had a stable ASM therapy during the first 2 years after the VNS implantation. Data were collected from the Mainz Epilepsy Registry. The efficacy of VNS depending on the concomitantly used ASM group/individual ASMs was assessed by quantifying the responder rate (≥ 50% seizure reduction compared to the time of VNS implantation) and seizure freedom (absence of seizures during the last 6 months of the observation period).ResultsOne hundred fifty one patients (mean age 45.2 ± 17.0 years, 78 females) were included in the study. Regardless of the used ASM, the responder rate in the whole cohort was 50.3% and the seizure freedom was 13.9%. Multiple regression analysis showed that combination of VNS with synaptic vesicle glycoprotein (SV2A) modulators (responder rate 64.0%, seizure freedom 19.8%) or slow sodium channel inhibitors (responder rate 61.8%, seizure freedom 19.7%) was associated with a statistically significant better responder rate and seizure freedom than combinations of VNS and ASM with other mechanism of action. Within these ASM groups, brivaracetam showed a more favorable effect than levetiracetam, whereas lacosamide and eslicarbazepine were comparable in their effects.ConclusionOur data suggest that the combination of VNS with ASMs belonging to either SV2A modulators or slow sodium channel inhibitors could be optimal to achieve a better seizure control following VNS. However, these preliminary data require further validation under controlled conditions.

Alteration of Excitation/Inhibition Imbalance in the Hippocampus and Amygdala of Drug-Resistant Epilepsy Patients Treated with Acute Vagus Nerve Stimulation.

An imbalance between excitation (E) and inhibition (I) in the brain has been identified as a key pathophysiology of epilepsy over the years. The hippocampus and amygdala in the limbic system play a crucial role in the initiation and conduction of epileptic seizures and are often referred to as the transfer station and amplifier of seizure activities. Existing animal and imaging studies reveal that the hippocampus and amygdala, which are significant parts of the vagal afferent network, can be modulated in order to generate an antiepileptic effect. Using stereo-electroencephalography (SEEG) data, we examined the E/I imbalance in the hippocampus and amygdala of ten drug-resistant epilepsy children treated with acute vagus nerve stimulation (VNS) by estimating the 1/f power slope of hippocampal and amygdala signals in the range of 1-80 Hz. While the change in the 1/f power slope from VNS-BASE varied between different stimulation amplitudes and brain regions, it was more prominent in the hippocampal region. In the hippocampal region, we found a flatter 1/f power slope during VNS-ON in patients with good responsiveness to VNS under the optimal stimulation amplitude, indicating that the E/I imbalance in the region was improved. There was no obvious change in 1/f power slope for VNS poor responders. For VNS non-responders, the 1/f power slope slightly increased when the stimulation was applied. Overall, this study implies that the regulation of E/I imbalance in the epileptic brain, especially in the hippocampal region, may be an acute intracranial effect of VNS.

ID: 208947 Ultrashort Microscopic Magnetic Vagal Stimulation

Electrical stimulation of the cervical vagus nerve is an emerging treatment field for various central nervous system disorders. Invasive electrical Vagus nerve stimulation (VNS) is an FDA-approved add-on treatment to medication for refractory partial-onset seizures in patients 12 years of age and older. However, only approximately 40-50% of patients experience a marked seizure reduction of 50% or more than seizures before treatment [1]. The effects of VNS on neurotransmitter systems, including the noradrenergic system originating from the locus coeruleus and the serotonergic system from the dorsal raphe nucleus, have been reported in experimental settings. The therapeutic effect of VNS in the brain is linked to the stimulation of large diameter afferent fibers. These large myelinated afferent fibers, terminating in the nucleus tractus solitarius in the brainstem, are assumed to deliver the therapeutic effect through further projections into the other brain areas. Non-selective stimulation results in inadvertent activation of efferent fibers that innervate a wide range of peripheral organs resulting in adverse effects [2] with a rare but severe risk of bradyarrhythmia and asystole.

ID: 219808 Towards Smart Vagus Nerve Stimulation for the Gastrointestinal System

Characterizing the physiological effects of neuromodulation is crucial for understanding the mechanism of action and developing effective and safe therapies. Vagus nerve stimulation (VNS) has been proposed as a potential treatment for gastrointestinal disorders (Li et al., 2017). However, its biological effects and therapeutic effectiveness are not fully understood. The purpose of this study was to create a data-driven framework for automated characterization of the VNS effects on the gastric function, measured by the features of electrogastrogram (EGG) recordings.

1019 New onset OSA after long term Vagus Nerve Stimulator implantation in a patient with Lennox-Gastaut syndrome: A case report

Abstract Introduction Implantable vagus nerve stimulation (VNS) is an established treatment for drug resistant epilepsy. New onset obstructive sleep apnea (OSA) is a rare side effect of VNS. There are few studies describing VNS induced sleep apnea in adults. [1-2] A study of 16 patients with drug-refractory epilepsy found 5 patients with normal AHI develop mild OSA after VNS treatment for 3 months. [2] However, no literature exists regarding OSA after long term VNS implantation. Untreated OSA in patients with epilepsy can impact epilepsy outcomes. We report a case of new onset OSA after long term VNS implantation, refractory to PAP therapy. Report of case(s) A 36 year-old man with Lennox-Gastaut syndrome presented with gasping during sleep and daytime hypersomnolence. He underwent VNS implantation at the age of 12. A prior PSG in 2018 showed no sleep apnea. Repeat PSG showed VNS-induced OSA (AHI 10.1/hour). After failed CPAP titration, BPAP-S at 25/16 cm H2O improved OSA. Review of therapy data on follow up showed AHI of 13.7/hour and CAI of 10.9/hour, which is concerning for treatment induced central sleep apnea on BPAP. Diagnostic study with VNS turned off revealed mild OSA (AHI 5.8/hour). A multidisciplinary approach involving ENT for drug-induced sleep endoscopy to optimize VNS stimulation parameters along with neurology and sleep involvement is planned. The optimized VNS setting could be used during planned sleep times using a VNS device with dual-programming capability. Conclusion To our knowledge, there is no literature on development of sleep apnea after long term VNS implantation. Although the exact mechanism is unknown, VNS can cause sleep apnea or worsen sleep apnea in patients with a preexisting diagnosis. [1] This case demonstrates need for continuous monitoring and screening for sleep apnea in patients who have been implanted with VNS, even if baseline and follow up PGSs are normal. Current literature suggests discontinuation of VNS to resolve VNS-induced OSA, but we describe a case here where VNS is needed for ongoing management of epilepsy. Further studies are needed to identify treatment options for patients that cannot discontinue VNS therapy who also cannot be successfully treated with PAP if they develop VNS-induced OSA. Support (if any)

Analgesic Effects of Vagus Nerve Stimulation on Visceral Hypersensitivity: A Direct Comparison Between Invasive and Noninvasive Methods in Rats

ObjectivesThe aims of this study were to investigate analgesic effects of vagus nerve stimulation (VNS) on visceral hypersensitivity (VH) in a rodent model of functional dyspepsia (FD) and to compare invasive VNS with noninvasive auricular VNS (aVNS). Materials and MethodsEighteen ten-day-old male rats were gavaged with 0.1% iodoacetamide (IA) or 2% sucrose solution for six days. After eight weeks, IA-treated rats were implanted with electrodes for VNS or aVNS (n = 6 per group). Different parameters, varying in frequency and stimulation duty cycle, were tested to find the best parameter based on the improvement of VH assessed by electromyogram (EMG) during gastric distension. ResultsCompared with sucrose-treated rats, visceral sensitivity was increased significantly in IA-treated “FD” rats and ameliorated remarkably by VNS (at 40, 60, and 80 mm Hg; p ≤ 0.02, respectively) and aVNS (at 60 and 80 mm Hg; p ≤ 0.05, respectively) with the parameter of 100 Hz and 20% duty cycle. There was no significant difference in area under the curve of EMG responses between VNS and aVNS (at 60 and 80 mm Hg, both p > 0.05). Spectral analysis of heart rate variability revealed a significant enhancement in vagal efferent activity while applying VNS/aVNS compared with sham stimulation (p < 0.01). In the presence of atropine, no significant differences were noted in EMG after VNS/aVNS. Naloxone blocked the analgesic effects of VNS/aVNS. ConclusionsVNS/aVNS with optimized parameter elicits ameliorative effects on VH, mediated by autonomic and opioid mechanisms. aVNS is as effective as direct VNS and has great potential for treating visceral pain in patients with FD.

Is thalamic deep brain stimulation synergistic with vagus nerve stimulation in drug-resistant genetic generalized epilepsy?

Neuromodulation in epilepsy is a proven treatment for people with drug-resistant focal epilepsy. Dual device therapies are increasingly utilized in people with drug-resistant epilepsy. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) target the thalamus involving the primary neurobiological network in patients with genetic generalized epilepsy (GGE). We report a novel case of combined neuromodulation in a patient with drug-resistant GGE who achieved a partial response with seizure reduction after VNS implantation yet following VNS-DBS polyneurostimulation gradually achieved prolonged seizure freedom. We speculate that by combining the indirect activating effects of VNS with the direct inhibitory effects of DBS, this may provide synergy to thalamic modulated networks. We hypothesize a "rational polytherapy" may exist in some patients with GGE undergoing dual neuromodulation.

USP10 is a potential mediator for vagus nerve stimulation to alleviate neuroinflammation in ischaemic stroke by inhibiting NF-κB signalling pathway.

Vagus nerve stimulation (VNS) has a protective effect on neurological recovery in ischaemic stroke. However, its underlying mechanism remains to be clarified. Ubiquitin-specific protease 10 (USP10), a member of the ubiquitin-specific protease family, has been shown to inhibit the activation of the NF-κB signalling pathway. Therefore, this study investigated whether USP10 plays a key role in the protective effect of VNS against ischemic stroke and explore its mechanism. Ischaemic stroke model was constructed by transient middle cerebral artery occlusion (tMCAO) in mice. VNS was performed at30 min,24hr, and 48hr after the establishment of tMCAO model. USP10 expression induced by VNS after tMCAO was measured. LV-shUSP10 was used to establish the model with low expression of USP10 by stereotaxic injection technique. The effects of VNS with or without USP10 silencing on neurological deficits, cerebral infarct volume, NF-κB pathway activation, glial cell activation, and release of pro-inflammation cytokines were assessed. VNS enhanced the expression of USP10 following tMCAO. VNS ameliorated neurological deficits and reduced cerebral infarct volume, but this effect was inhibited by silencing of USP10. Activation of the NF-κB pathway and the expression of inflammatory cytokines induced by tMCAO were suppressed by VNS. Moreover, VNS promoted the pro-to-anti-inflammatory response of microglia and inhibited activation of astrocytes, while silencing of USP10 prevented the neuroprotective and anti-neuroinflammatory effects of VNS. USP10 is a potential mediator for VNS to alleviate neurological deficits, neuroinflammation, and glial cell activation in ischaemic stroke by inhibiting NF-κB signalling pathway.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d=-0.31), increase in N3 sleep (d=0.23), and a small-to-moderate decrease in REM sleep (d=-0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d=-0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

The Effects of Vagus Nerve Stimulation on Animal Models of Stroke-Induced Injury: A Systematic Review.

Ischemic stroke is one of the leading causes of death worldwide, and poses a great burden to society and the healthcare system. There have been many recent advances in the treatment of ischemic stroke, which usually results from the interruption of blood flow to a particular part of the brain. Current treatments for ischemic stroke mainly focus on revascularization or reperfusion of cerebral blood flow to the infarcted tissue. Nevertheless, reperfusion injury may exacerbate ischemic injury in patients with stroke. In recent decades, vagus nerve stimulation (VNS) has emerged as an optimistic therapeutic intervention. Accumulating evidence has demonstrated that VNS is a promising treatment for ischemic stroke in various rat models through improved neural function, cognition, and neuronal deficit scores. We thoroughly examined previous evidence from stroke-induced animal studies using VNS as an intervention until June 2022. We concluded that VNS yields stroke treatment potential by improving neurological deficit score, infarct volume, forelimb strength, inflammation, apoptosis, and angiogenesis. This review also discusses potential molecular mechanisms underlying VNS-mediated neuroprotection. This review could help researchers conduct additional translational research on patients with stroke.