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AIMS: Prior case series showed promising results for cardioneuroablation in patients with vagally induced atrioventricular blocks (VAVBs). We aimed to examine the acute procedural characteristics and intermediate-term outcomes of electroanatomical-guided cardioneuroablation (EACNA) in patients with VAVB. METHODS AND RESULTS: This international multicentre retrospective registry included data collected from 20 centres. Patients presenting with symptomatic paroxysmal or persistent VAVB were included in the study. All patients underwent EACNA. Procedural success was defined by the acute reversal of atrioventricular blocks (AVBs) and complete abolition of atropine response. The primary outcome was occurrence of syncope and daytime second- or advanced-degree AVB on serial prolonged electrocardiogram monitoring during follow-up. A total of 130 patients underwent EACNA. Acute procedural success was achieved in 96.2% of the cases. During a median follow-up of 300 days (150, 496), the primary outcome occurred in 17/125 (14%) cases with acute procedural success (recurrence of AVB in 9 and new syncope in 8 cases). Operator experience and use of extracardiac vagal stimulation were similar for patients with and without primary outcomes. A history of atrial fibrillation, hypertension, and coronary artery disease was associated with a higher primary outcome occurrence. Only four patients with primary outcome required pacemaker placement during follow-up. CONCLUSION: This is the largest multicentre study demonstrating the feasibility of EACNA with encouraging intermediate-term outcomes in selected patients with VAVB. Studies investigating the effect on burden of daytime symptoms caused by the AVB are required to confirm these findings.

Stroke is a significant health concern impacting society and the health care system. Reperfusion therapy for acute ischemic stroke and standard rehabilitative therapies may not always be effective at improving post-stroke neurological function, and developing alternative strategies is particularly important. Vagus nerve stimulation (VNS) is a treatment option currently approved by the Food and Drug Administration (FDA) for intractable epilepsy, refractory depression, primary headache disorders, obesity, and moderate to severe upper-limb motor dysfunction in chronic ischemic stroke patients. Moreover, VNS has demonstrated potential efficacy in various conditions, including autoimmune diseases, disorders of consciousness, Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke, and other diseases. Although the popularity and application of VNS continue to increase rapidly, the field generally lacks a consensus on the optimal stimulation parameters. The stimulation parameters for VNS are directly related to the clinical outcome, and determining the optimal stimulation conditions for VNS has become an essential concern in its clinical application. This review summarizes the current evidence on VNS for stroke in preclinical models and clinical trials in humans, paying attention to the current types and stimulation parameters of VNS, highlighting the mechanistic pathways involved in the beneficial effects of VNS, critically evaluating clinical implementation challenges and proposing some suggestions for its future research directions. Achieving safe and effective clinical transformation of VNS requires further animal and clinical studies to determine the optimal stimulation parameters and therapeutic mechanisms. [ABSTRACT FROM AUTHOR]

Background: Depersonalization-derealization disorder (DPD) is a complex psychiatric condition marked by profound and often relentless feelings of detachment from one's self and surroundings. Transcranial electrical stimulation (taVNS) holds promise as a potential therapeutic approach for DPD. This study aims to investigate the safety and efficacy of taVNS in treating DPD. Methods: DPD patients were recruited as research subjects and randomly allocated to the experimental and control groups, with the former receiving active-taVNS treatment and the latter receiving sham stimulation treatment for 6 weeks. The efficacy of taVNS in treating DPD was evaluated by comparing scores for DPD symptoms, depression and anxiety symptoms, cognitive function, and social function before and after treatment between the two groups. The safety of taVNS in treating DPD was assessed by comparing general safety assessment results between the two groups of DPD patients. Discussion: This study will assess taVNS as a potential treatment for DPD, evaluating its safety, efficacy, and impact on patient outcomes and societal burden. Trial registration: Chinese Clinical Trial Registry, ChiCTR2300078183, Registered on 30 November, 2023, https://www.chictr.org.cn/showproj.html?proj=206119 [ABSTRACT FROM AUTHOR]

Background: Current inflammatory bowel disease (IBD) treatments often fail to achieve lasting remission and have adverse effects. Vagus nerve stimulation (VNS) offers a promising therapy due to its anti-inflammatory effects. Its invasive nature, however, has led to the development of non-invasive methods like transcutaneous auricular VNS (taVNS). This study assesses taVNS's impact on acute colitis progression, inflammatory, anti-inflammatory, and apoptosis-related markers. Methods: Male C57BL/6 mice (11–12 weeks) were used for dextran sulfate sodium (DSS)- and dinitrobenzene sulfonic acid (DNBS)-induced colitis studies. The administration of taVNS or no stimulation (anesthesia without stimulation) for 10 min per mouse began one day before colitis induction and continued daily until sacrifice. Ulcerative colitis (UC)-like colitis was induced by administering 5% DSS in drinking water for 5 days, after which the mice were sacrificed. Crohn's disease (CD)-like colitis was induced through a single intrarectal injection of DNBS/ethanol, with the mice sacrificed after 3 days. Disease activity index (DAI), macroscopic evaluations, and histological damage were assessed. Colon, spleen, and blood samples were analyzed via qRT-PCR and ELISA. One-way or two-way ANOVA with Bonferroni and Šídák tests were applied. Results: taVNS improved DAI, macroscopic, and histological scores in DSS colitis mice, but only partially mitigated weight loss and DAI in DNBS colitis mice. In DSS colitis, taVNS locally decreased colonic inflammation by downregulating pro-inflammatory markers (IL-1β, TNF-α, Mip1β, MMP 9, MMP 2, and Nos2) at the mRNA level and upregulating anti-inflammatory TGF-β in non-colitic conditions at both mRNA and protein levels and IL-10 mRNA levels in both non-colitic and colitic conditions. Systemically, taVNS decreased splenic TNF-α in non-colitic mice and increased serum levels of TGF-β in colitic mice and splenic levels in non-colitic and colitic mice. Effects were absent in DNBS-induced colitis. Additionally, taVNS decreased pro-apoptotic markers (Bax, Bak1, and caspase 8) in non-colitic and colitic conditions and increased the pro-survival molecule Bad in non-colitic mice. Conclusions: This study demonstrates that taVNS has model-dependent local and systemic effects, reducing inflammation and apoptosis in UC-like colitis while offering protective benefits in non-colitic conditions. These findings encourage further research into underlying mechanisms and developing adjunct therapies for UC. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is an established therapy for drug‐resistant epilepsy. However, there is a lack of reliable predictors of VNS response in clinical use. The identification of factors predictive of VNS response is important for patient selection and stratification as well as tailored stimulation programming. We conducted a narrative review of the existing literature on prognostic markers for VNS response using clinical, demographic, biochemical, and modality‐specific information such as from electroencephalography (EEG), magnetoencephalography, and magnetic resonance imaging (MRI). No individual marker demonstrated sufficient predictive power for individual patients, although several have been suggested, with some promising initial findings. Combining markers from underresearched modalities such as T1‐weighted MRI morphometrics and EEG may provide better strategies for treatment optimization. [ABSTRACT FROM AUTHOR]

Patients diagnosed with heart failure have high rates of mortality and morbidity. Based on promising preclinical studies, vagal nerve stimulation has been trialled in these patients using whole nerve electrical stimulation, but the results have been mixed. This is, at least in part, due to an inability to selectively recruit the activity of specific fibres within the vagus with whole nerve electrical stimulation, as well as not knowing which the 'therapeutic' fibres are. This symposium review focuses on a population of cardiac‐projecting efferent vagal fibres with cell bodies located within the dorsal motor nucleus of the vagus nerve and a new method of selectively targeting these projections as a potential treatment in heart failure. What is the topic of this review?Selective efferent vagal stimulation in heart failure.What advances does it highlight?Selectively targeting a population of cardiac‐projecting efferent vagal fibres with cell bodies within the dorsal motor nucleus of the vagus using optogenetics slows the progression of heart failure in rats. [ABSTRACT FROM AUTHOR]

Introduction: Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. Methods: A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS—needle electrodes) and transcutaneous (tVNS—surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. Results: A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of − 1.95 (95% confidence interval [CI]: − 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (− 5.40 [− 8.94; − 1.85] vs. − 1.00 [− 1.55; − 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with − 0.70 [− 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. Conclusion: This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Conditioned pain modulation (CPM) is a quantitative estimation of the capacity for endogenous pain modulation. Reduced CPM enables chronic painful event development or exacerbates pre-existing pain symptoms. Emerging reports indicate that patients with trigeminal neuralgia (TN) have dysregulated endogenous pain modulation. Transauricular vagus nerve stimulation (taVNS) is known to alleviate both acute and chronic pain symptoms. Its role in modulation or management of TN remains unknown. Here, we evaluated the taVNS efficacy in modulating CPM among TN patients. Conclusions from this investigation may facilitate establishment of novel non-invasive adjunctive approaches to treating TN patients. Methods: All research work was conducted at the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). In all, we recruited 62 study participants, 31 TN patients and 31 healthy volunteers, for a 2-day experimental test. At the beginning of the experiment (Day 1), all subjects received 30 min of active taVNS. On Day 2, they received sham taVNS with the same duration and intensity. Meanwhile, technicians documented participant pressure pain thresholds (PPT) and CPM values at baseline, and at 15 and 30 min post-active or sham taVNS. Results: A 30-min active taVNS exposure substantially elevated the PPT and CPM effect (P < 0.05) among TN patients, and we also observed a notable rise in the PPT and CPM effect (P < 0.05) among healthy controls. Additionally, there were no serious adverse events from the administered treatment. Conclusion: Exposure to 30 min of active taVNS strongly augmented the CPM effect and elevated the PPT among TN patients and healthy controls. These effects were not observed with sham stimulation. Despite the limitations inherent to survey studies, such as duration and compliance biases, we consider that taVNS is a promising, safe, and cost-effective therapy. In future investigations, we recommend assessment of long-term taVNS application and its effects on CPM and clinical pain. Trial Registration: ChiCTR2300078673 (www.Chictr.org.cn). [ABSTRACT FROM AUTHOR]

The article discusses the concept of combination treatment in managing migraine, which involves using two or more acute or preventive treatments simultaneously. It emphasizes the importance of clear terminology to enhance communication and implementation of treatment strategies, especially in regions with diverse practices. The text highlights the need for a standardized lexicon among clinicians and researchers to improve patient care and reduce ambiguity in the field. The authors suggest a stepwise approach to combining treatments, starting with identifying a baseline treatment and layering subsequent treatments based on individual patient characteristics and disease burden. [Extracted from the article]

Purpose: Vagus nerve stimulation (VNS) is emerging as a unique and potent intervention, particularly within neurology and psychiatry. The clinical value of VNS continues to grow, while the development of noninvasive options promises to change a landscape that is already quickly evolving. In this review, we highlight recent progress in the field and offer readers a glimpse of the future for this bright and promising modality. Methods: We compiled a narrative review of VNS literature using PubMed and organized the discussion by disease states with approved indications (epilepsy, depression, obesity, post-stroke motor rehabilitation, headache), followed by a section highlighting novel, exploratory areas of VNS research. In each section, we summarized the current role, recent advancements, and future directions of VNS in the treatment of each disease. Results: The field continues to gain appreciation for the clinical potential of this modality. VNS was initially developed for treatment-resistant epilepsy, with the first depression studies following shortly thereafter. Overall, VNS has gained approval or clearance in the treatment of medication-refractory epilepsy, treatment-resistant depression, obesity, migraine/cluster headache, and post-stroke motor rehabilitation. Conclusion: Noninvasive VNS represents an opportunity to bridge the translational gap between preclinical and clinical paradigms and may offer the same therapeutic potential as invasive VNS. Further investigation into how VNS parameters modulate behavior and biology, as well as how to translate noninvasive options into the clinical arena, are crucial next steps for researchers and clinicians studying VNS. [ABSTRACT FROM AUTHOR]

• Surveillance MRI is needed to monitor for TSC associated renal angiomyolipomas. • However, MRI of the abdomen is not approved for patients with VNS therapy. • We studied abdominal MRIs performed in typical VNS exclusion zones. • We found they were not associated with adverse events or VNS dysfunction. Individuals with tuberous sclerosis complex (TSC) often present with refractory epilepsy and may be undergoing treatment with vagus nerve stimulation (VNS) to control seizures. Surveillance magnetic resonance imaging (MRI) is necessary to monitor for the renal angiomyolipomas associated with TSC; however, MRI of the abdomen is not approved for patients withVNS therapy. We have many TSC patients with refractory epilelpsy who benefitted from VNS therapy, so we developed an MRI protocol that allows MRI of the abdomen to be performed in these patients to permit safe imaging of their kidneys. Here we report our results using this protocol. We performed a retrospective review for all TSC patients seen from 01/01/1997 to 10/01/2022 at a single center to determine VNS implantation status. Patients with VNS implants and abdomen imaging performed according to the protocol for kidney surveillance were included. Sixteen patients with 48 total MRIs of the abdomen were found: 34 (71 %) scans were conducted under sedation and 14 (29 %) without sedation. None of the patients reported any adverse effects (pain or discomfort). No instances of VNS dysfunction were noted when re-interrogating the device immediately after completion of the imaging studies or at later neurology follow-up appointments. All MRI scans were of good quality for interpretation. Abdominal MRIs performed in typical VNS exclusion zones were not associated with adverse events or VNS dysfunction. We believe this protocol is safe and permits the best method for monitoring renal disease in TSC patients with VNS. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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. Results: 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. Conclusions: These results add to our understanding of how VNS exerts its beneficial effects in drug‐resistant epilepsy. Plain Language Statement: 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, which contributes to our understanding of how VNS works in the context of drug‐resistant epilepsy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of vagus nerve stimulation (VNS) on seizure control, cognitive functions, and quality of life in individuals with drug‐resistant epilepsy. Methods: An extensive search of electronic databases was carried out in order to carry out this systematic review. The databases Google Scholar, Embase, PubMed, and the Cochrane Library were searched first to carryout gray literature. To reduce the quantity of pointless studies in the advanced search, the search is limited to "human studies" and "English language" publications only. Combining keywords and Medical Subject Headings (MeSH) terms like ("Vagus Nerve Stimulation" OR "VNS") AND ("Epilepsy" OR "Seizure Control") AND ("Cognitive Function" OR "Quality of Life"). Studies that have been published up to November 30/2023 were included. Results: The search strategy yielded a total of 392 relevant studies. The mean age of participant's ranges from 11 years to 33 years. The duration of follow‐up ranging from 6 to 36 months. Eleven studies were included in the review. The mean≥50% response rate after VNS therapy was 56.94% ranged from 48.90% to 83.00%. Four and three studies provided information about Quality of Life in Epilepsy Inventory (QOLIE‐31) and The Liverpool Seizure Severity Scale (LSSS) questionnaires respectively. Significance: Epilepsy is a chronic disease characterized by sudden abnormal discharge of brain neurons, which leads to transient brain dysfunction and the presence of spontaneous recurrent seizures. Vagus nerve stimulation has recently been proposed as a potential tool in the treatment of seizure, depressive symptoms, and cognitive impairments. There has been variation in the effects of VNS treatment on seizure control, cognitive functions, and quality of life among patients with drug‐resistant epilepsy. So, a comprehensive review of exciting literature is important to see the pooled effect. Previous systematic review and meta‐analysis papers were mostly randomized control trial type with specific diseases. The use of a wider variety of study designs than only randomized controlled trials is important. So, we included retrospective and prospective cohort studies in addition to randomized control trials. This enables a more thorough assessment of the connection between quality of life, cognitive function, and vagus nerve stimulation. In addition, the paper looks at a wide range of disease kinds and patterns. We have established a uniform and comprehensive approach throughout the selected studies by mandating the inclusion of all three crucial parameters: vagus nerve stimulation, cognitive function, and quality of life. Plain Language Summary: This systematic review examined 392 relevant studies on vagus nerve stimulation (VNS) therapy, with participants ranging from 11 to 33 years old and follow‐up durations of 6–36 months. Eleven studies were included, and the mean response rate after VNS therapy was 56.94%, ranging from 48.90% to 83.00%. The review also reported on quality of life and cognitive function, and seizure severity frequency result from several studies. [ABSTRACT FROM AUTHOR]

Objective: Amount of seizure‐free days is a critical determinant of quality of life (QoL) in patients with drug‐resistant epilepsy (DRE). The fractions of patients experiencing prolonged periods of seizure freedom with adjunctive vagus nerve stimulation (VNS) have yet to be assessed on a large scale. Methods: Retrospective analysis of patients in the Japanese VNS prospective observational registry who experienced at least 1 year of seizure freedom from all seizures, focal seizures, or tonic–clonic seizures (TCS), as well as patient‐reported change in QoL in these groups. Results: The study included 362 patients with DRE, 147 were female (40.6%), and the median age at VNS implant was 23.0 years (range: 1.0–73.0). A total of 225 patients reported focal seizures and 184 patients reported TCS. After 36 months of adjunctive VNS, the cumulative proportion of patients experiencing at least 1 year of complete seizure freedom was 11% (38/356) with an average duration of seizure freedom of 19.4 months. In patients with focal seizures, 25% (n = 57/225) experienced at least 1 year of freedom from focal seizures with an average duration of 24.8 months. Higher cumulative rates of freedom from TCS were observed: 55% (n = 101/184) experienced at least 1 year without TCS with an average duration of TCS‐free periods of 28.9 months. 82.1% of patients with 12‐month complete seizure freedom reported markedly improved or improved QoL compared with 51.9% of patients who were not seizure‐free. QoL changes in patients with 12‐month seizure freedom from TCS and focal seizures were similar: 61.8% and 63% of respective patients reported either markedly improved or improved QoL at 36 months. Significance: Complete seizure freedom is rare in patients treated with VNS; however, this analysis found approximately half of patients who experienced TCS prior to VNS experienced prolonged periods of freedom from TCS with adjunctive VNS. Plain Language Summary: We studied patients in Japan with epilepsy that is difficult to treat. To understand if adding vagus nerve stimulation (VNS) helps such patients, we looked at which patients stopped having all seizures or stopped having a specific seizure type (such as tonic–clonic seizures or focal seizures), and how long these periods lasted. With VNS treatment, about 2 out of 4 patients with tonic–clonic seizures and 1 out of 4 patients with focal seizures had more time without these seizure types. Without seizures, patients felt better about their daily lives. Even patients who still had seizures felt better about their daily lives after 3 years of VNS treatment. Trial Registration: The clinical trial registry number is UMIN000014728. [ABSTRACT FROM AUTHOR]

After esophagectomy, an imbalanced inflammatory response increases the risk of postoperative morbidity. The vagus nerve modulates local and systemic inflammatory responses, but its pulmonary branches are transected during esophagectomy as part of the oncological resection, which may account for the high incidence of postoperative (pulmonary) complications. This study investigated the effect of electrical vagus nerve stimulation (VNS) on lipopolysaccharide (LPS)-induced lung injury in rats. Rats (n = 60) were randomly assigned to a non-vagotomy or cervical vagotomy group, with VNS or without (NOSTIM). There were four non-vagotomy groups: NOSTIM and bilateral VNS with 100, 50, or 10 µA. The four vagotomy groups were NOSTIM and VNS with fixed amplitude (50 µA) bilaterally before (VNS-50-before) or after bilateral vagotomy (VNS-50-after), or unilaterally (left) before ipsilateral vagotomy (VNS-50-unilaterally). LPS was administered intratracheally after surgery. Pulmonary function, pro-inflammatory cytokines in serum, broncho-alveolar lavage fluid (BALF), and histopathological lung injury (LIS) were assessed 180 min post-procedure. In non-vagotomized rats, neutrophil influx in BALF following intra-tracheal LPS (mean 30 [± 23]; P = 0.075) and LIS (mean 0.342 [± 0.067]; P = 0.142) were similar after VNS-100, compared with NOSTIM. VNS-50 reduced neutrophil influx (23 [± 19]; P = 0.024) and LIS (0.316 [± 0.093]; P = 0.043). VNS-10 reduced neutrophil influx (15 [± 6]; P = 0.009), while LIS (0.331 [± 0.053]; P = 0.088) was similar. In vagotomized rats, neutrophil influx (52 [± 37]; P = 0.818) and LIS (0.407 [SD ± 0.037]; P = 0.895) in VNS-50-before were similar compared with NOSTIM, as well as in VNS-50-after (neutrophils 30 [± 26]; P = 0.090 and LIS 0.344 [± 0.053]; P = 0.073). In contrast, VNS-50-unilaterally reduced neutrophil influx (26 [± 10]; P = 0.050) and LIS (0.296 [± 0.065]; P = 0.005). Systemic levels of cytokines TNF-α and IL-6 were undetectable in all groups. Pulmonary function was not statistically significantly affected. In conclusion, VNS limited influx of neutrophils in lungs in non-vagotomized rats and may attenuate LIS. Unilateral VNS attenuated lung injury even after ipsilateral vagotomy. This effect was absent for bilateral VNS before and after bilateral vagotomy. It is suggested that the effect of VNS is dependent on (partially) intact vagus nerves and that the level of the vagotomy during esophagectomy may influence postoperative pulmonary outcomes. [ABSTRACT FROM AUTHOR]

Aim: Polycystic ovary syndrome (PCOS) is an increasingly recognized endocrine disorder. The pathogenesis is not fully known. Polycystic ovary syndrome is still difficult to diagnose correctly, despite simple diagnostic criteria. The aim of the study is to review the current knowledge about PCOS and treatment options for patients with the disease. To explore this topic, publications were reviewed and conclusions drawn from them. The incidence of hyperandrogenism in a patient with PCOS may be as high as 60-80%. Increased androgen levels affect ovulation and menstruation, and also result in hirsutism and acne. Additionally, patients have problems with proper glucose tolerance (insulin resistance), type 2 diabetes, hypertension, cardiovascular diseases and metabolic syndrome. PCOS results in various symptoms in patients. Methods: The latest treatment methods were analysed. A standard review of publications in the field of diagnosis and treatment of PCOS, IR and hyperandrogenism was used. Results: Lifestyle, especially diet, deserves special attention due to its ease of use. Sleep quality, physical activity and stress reduction are also important. Diet should be the treatment of first choice. Only if dietary intervention does not bring results, the doctor considers pharmacotherapy. Recently, acupuncture and herbal medicine, vagus nerve stimulation have been used in the treatment of PCOS and regulation of hormone levels. Patients are given supplementation to improve the quality of functioning, but it must be remembered that inappropriate doses or too long use may result in a toxic effect opposite to the therapeutic one. Conclusion: Appropriate diet, physical activity - lifestyle changes are crucial in the treatment of PCOS. Supplementation and pharmaceuticals support treatment. It is mandatory to examine these environmental and lifestyle factors as they not only contribute to the occurrence of the disease but also influence its progression. [ABSTRACT FROM AUTHOR]

Interoception, the perception of visceral sensations, is key for several survival functions, including those related to feeding behavior. Sensations of hunger and satiety are mediated by gastric signals transmitted via the vagus nerve to the Nucleus of Solitary Tract. Transcutaneous auricular vagus nerve stimulation (taVNS) has been shown to modulate brain‐viscera communication and to impact interoceptive processing in the cardiac domain. Yet, its effect on gastric interoception remains unclear. The aim of this study was to investigate taVNS' modulatory effects on gastric interoception using the Water Load Test‐II (WLT‐II) and its impact on food‐related dispositions through a disposition and willingness to eat task (DWET). Participants underwent active or sham taVNS while performing the WLT‐II and DWET. Results showed no significant difference in gastric interoceptive accuracy and amount of water ingested between taVNS groups. However, we found a significant reduction in food liking after the fullness phase of the WLT‐II in the active (vs sham) taVNS group, suggesting an influence of vagal activation in the inhibition of food enjoyment when satiated. These findings suggest that, while taVNS may not directly enhance gastric interoceptive accuracy at a conscious level, it influences food‐related dispositions, likely by modulating the processing of gastric signals. Further research exploring the intricate relationship between vagal modulation, interoceptive abilities and eating behaviors is warranted to elucidate the underlying mechanisms and, possibly, develop targeted interventions for eating disorders. [ABSTRACT FROM AUTHOR]

Depression, a prevalent neuropsychiatric disorder, involves the dysregulation of neurotransmitters such as dopamine (DA). The restoration of DA balance is a pivotal therapeutic target for this condition. Recent studies have indicated that both antidepressant medications and non-pharmacological treatments, such as transcutaneous auricular vagus nerve stimulation (taVNS), can promote recovery from depressive symptoms. Despite the promise of taVNS as a non-invasive depression therapy, its precise mechanism remains unclear. We hypothesized that taVNS exerts antidepressant effects by modulating the DAergic system. To investigate this, we conducted experiments demonstrating that taVNS in anesthetized mice reduced depressive-like behaviors. However, this effect was abolished when DA neurons in the ventral tegmental area (VTADA) were inhibited. Additionally, taVNS in anesthetized mice enhanced VTADA activity, providing further evidence to support its antidepressant effects. Overall, our findings suggest that taVNS alleviates depression by augmenting VTADA activity, thereby contributing to a more comprehensive understanding of its therapeutic mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Pairing vagus nerve stimulation with traditional rehabilitation therapies results in improved motor recovery in people with stroke. However, this approach has not yet been studied in people with spinal cord injury (SCI). Motor recovery continues to be challenging after SCI, and there is a need for innovative research strategies to enhance motor recovery after SCI. Hence, this pilot randomized controlled trial aims to evaluate the safety, feasibility, and potential efficacy of pairing vagus nerve stimulation (VNS) with rehabilitation therapy to restore the motor function of the paretic upper limbs in people with cervical SCI. Methods and analysis: In this triple-blind, randomized, sham-controlled pilot study, 8 adults with chronic incomplete SCI will be implanted with a VNS device and randomly assigned to either active VNS (0.8 mA) control VNS (0.0 mA) paired with upper limb rehabilitation. Each participant will undergo 18 in-clinic therapy sessions over 6 weeks, each lasting 120 min and delivered three times per week. Following the in-clinic phase, participants will continue with a 90-day home exercise program. Participants in both groups will receive similar goal-directed and intense upper limb rehabilitation. The therapy is focused on active movements, task specificity, high number repetitions, variable practice, and active participant engagement. Post-treatment assessment will occur immediately after in-clinic therapy and at 30 and 90 days of follow-up. After completion of blinding at 90 days follow-up, participants in the control group will be offered 6 weeks of in-clinic active VNS (0.8 mA) paired with rehabilitation. The safety of pairing VNS with rehabilitation will be assessed by the occurrence of adverse events in each group, and feasibility by the number of treatment sessions and follow-up visits attended and the number of dropouts. Potential efficacy will be assessed by measuring the change in Graded Redefined Assessment of Strength, Sensibility and Prehension (GRASSP) performance from baseline to immediately after in-clinic therapy and to 90 days. Secondary clinical outcome measures are the Toronto Rehabilitation Institute Hand Function Test, Capabilities of Upper Extremity Questionnaire, Spinal Cord Injury Independence Measure-III self-care subscore, and Spinal Cord Injury-Quality of Life scale. Ethics and dissemination: The trial protocol was approved by the Institutional Review Board of UTHealth (HSC-MS-22-0579). We anticipate publishing the results in a peer-reviewed journal within 1 year of study completion. Clinical trial registration: ClinicalTrials.gov, NCT05601661. [ABSTRACT FROM AUTHOR]

Non-invasive vagus nerve stimulation (VNS) represents a transformative approach for managing a broad spectrum of inflammatory and autoimmune conditions, including rheumatoid arthritis and inflammatory bowel disease. This comprehensive review delineates the mechanisms underlying VNS, emphasizing the cholinergic anti-inflammatory pathway, and explores interactions within the neuro-immune and vagus-gut axes based on both clinical outcomes and pre-clinical models. Clinical applications have confirmed the efficacy of VNS in managing specific autoimmune diseases, such as rheumatoid arthritis, and chronic inflammatory conditions like inflammatory bowel disease, showcasing the variability in stimulation parameters and patient responses. Concurrently, pre-clinical studies have provided insights into the potential of VNS in modulating cardiovascular and broader inflammatory responses, paving the way for its translational application in clinical settings. Innovations in non-invasive VNS technology and precision neuromodulation are enhancing its therapeutic potential, making it a viable option for patients who are unresponsive to conventional treatments. Nonetheless, the widespread adoption of this promising therapy is impeded by regulatory challenges, patient compliance issues, and the need for extensive studies on long-term efficacy and safety. Future research directions will focus on refining VNS technology, optimizing treatment parameters, and exploring synergistic effects with other therapeutic modalities, which could revolutionize the management of chronic inflammatory and autoimmune disorders. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a highly prevalent sleep disorder with substantial impacts on health and quality of life. Current treatment options have certain limitations, highlighting the need for novel therapeutic approaches. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is gaining recognition as a promising non-invasive neuromodulation technique for treating insomnia, but its efficacy has not been systematically evaluated. Therefore, this protocol outlines the framework for a systematic review and meta-analysis designed to comprehensively assess the effectiveness and safety of ta-VNS in treating primary insomnia. Methods: A thorough literature search will be carried out in Embase, PubMed, the Cochrane Library, PsycINFO, AMED, PEDro, Wangfang database, Chinese National Knowledge Infrastructure, and Chinese BioMedical Literature Database, covering publications from their inception until December 31, 2024. Randomized controlled trials evaluating ta-VNS for primary insomnia in adults will be included. Two independent reviewers will screen studies, gather data, and evaluate the risk of bias based on the Cochrane RoB 2.0 tool. Meta-analyses will be conducted where appropriate, and the quality of evidence will be evaluated using GRADE. Subgroup and sensitivity analyses are planned. Discussion: This systematic review and meta-analysis will deliver a thorough synthesis of existing evidence regarding the efficacy and safety of ta-VNS for insomnia, potentially informing clinical practice and future research directions. Trial registration: PROSPERO registration number:CRD42024529039. [ABSTRACT FROM AUTHOR]

Background: Melatonin (MLT) and its receptor deficiency have been shown to be associated with type 2 diabetes mellitus (T2DM). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive alternative intervention for patients suffering from hyperglycemia. Here, we aimed to investigate the role of taVNS on blood glucose modulation via intestinal melatonin receptors (MRs) and MLT secretion in hyperglycemia. Methods: Adult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. Forty ZDF rats were randomized into ZDF, taVNS, Px + taVNS and Lu + Px + taVNS groups (Px: pinealectomy, Lu: Luzindole). ZL rats served as a control group for comparison with ZDF rats without involvement in the taVNS intervention. Thirty min-taVNS interventions (2/15 Hz, 2 mA, 30 min/days) were administered once daily under anesthesia for 3 consecutive weeks in taVNS, Px + taVNS and Lu + Px + taVNS groups. Body weight and fasting blood glucose (FBG) were measured weekly in all rats, and real-time blood glucose was tested in the ZL and ZDF groups before, during and after the taVNS intervention. Plasma MLT concentration and the expression of MRs in the duodenum, jejunum and ileum were measured by the end of experiments. Results: Compared with the ZL group, the level of FBG and body weight increased (all p < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all p < 0.05), respectively. TaVNS can significantly reverse the hyperglycemia by regulating the non-pineal-derived MLT and MRs system in Px + taVNS group. Compared with the ZDF group, the expression of different intestinal MRs in the taVNS group was increased and more compactly arranged (both p < 0.05), the level of plasma MLT secretion was up-regulated (p < 0.01), and FBG and body weight were decreased (both p < 0.01). Meanwhile, after taVNS intervention in rats in the Px + taVNS group, we observed an increase in MLT secretion and the number of intestinal MRs compared with the taVNS group (all p > 0.05). In contrast, ZDF rats in which the pineal gland was excised by taVNS intervention and injected with the MRs antagonist Luzindole did not show these changes. Conclusion: The glucose reduction effect of taVNS may be related to regulating MLT levels and expressing intestinal MRs. [ABSTRACT FROM AUTHOR]

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. Editor's summary: Inflammatory bowel diseases (IBDs) are common and often severe chronic conditions; however, the underlying pathogenic mechanisms are not fully understood. Here, Youssef and colleagues found that decreased autonomic parasympathetic tone worsened susceptibility and mortality in mouse models of colitis, which were ameliorated by electrical stimulation of the vagus nerve. The mechanism of this amelioration involved inhibition of SUMOylation, and global knockout of small ubiquitin-like modifier 1 (Sumo1) or Sumo3 revealed resistance to disease progression and disease onset, respectively. The effects of vagus nerve stimulation were replicated through the administration of an inhibitor of the SUMO-activating enzyme in three mouse models of IBD, supporting inhibition of SUMOylation as a potential therapy for patients with these diseases. —Melissa L. Norton [ABSTRACT FROM AUTHOR]

Background/Objectives: Better understanding of and addressing umbilical entanglement in the third trimester of pregnancy is necessary to estimate its impact on fetal circulation. An analysis of single physiological pregnancies wrapped with one or two coils of the umbilical cord around the neck makes it possible to understand the severity of the problem and distinguish it from perinatal umbilical strangulation. Methods: In an echocardiographic study performed at 32.1 weeks of pregnancy in fetuses with one and two coils of the umbilical cord around the neck, the pulsatility index (PI) and the Tei index for the left (Tei LV) and right ventricle (Tei RV) of the heart were measured to evaluate cardiac function. Results: The study showed significantly higher Tei RV and Tei LV for fetuses with one (93 cases) and two coils of the umbilical cord around the fetal neck (26 cases) with respect to the control group of fetuses (680 cases) with no umbilical cord around the fetal neck, whereas PI UMBA did not differ significantly. Conclusions: Wrapping of the umbilical cord around the fetal neck may affect the study of the fetal heart without any mechanically induced compression of the umbilical vessels in normal pregnancy. [ABSTRACT FROM AUTHOR]

Purpose: Simulator Adaptation Syndrome arises from a perceptual discordance between expected and actual motion, giving rise to symptoms such as nausea and disorientation. This research focused on determining the benefit of Transcutaneous Vagal Nerve Stimulation (tVNS) and Galvanic Cutaneous Stimulation (GCS), where both were applied in conjunction, as compared to their administration in isolation, to decrease Simulator Adaptation Syndrome (SAS). Method: A driving simulation study was proposed where SAS, body balance, and driving performance were measured. These measurements were taken during seven different stimulation scenarios with a baseline condition without stimulation compared against tVNS and GCS conditions. Results: The main result showed that the combination of tVNS and GCS reduced SAS and improved body balance and driving performance more successfully than their administration in isolation. Conclusion: Similar neuromodulation in the temporoparietal junction is proposed to mitigate SAS for GCS and tVNS (although additional explanations are discussed). Applying both techniques simultaneously is encouraged to decrease SAS in future interventions. [ABSTRACT FROM AUTHOR]

The editorial titled "How does brain stimulation work? Neuroversion and other putative mechanisms of action" explores the evolving field of brain stimulation techniques in psychiatry and neurology. It discusses various methods such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS) that trigger neurochemical and electrophysiological changes in the brain to produce therapeutic effects. The research topic includes 10 articles authored by 76 individuals covering a range of brain stimulation techniques and their applications in neuropsychiatric disorders, aiming to enhance understanding and influence further research and clinical practice. The findings presented in the editorial highlight the diverse applications of brain stimulation techniques and their potential benefits, contributing to the advancement of clinical practice and stimulating further investigation into the mechanisms underlying these therapies. [Extracted from the article]

Anxiety is an increasingly prevalent mental disorder, causing widespread hardship and interfering with society's economic progression. Standard treatments include various talk therapies with poor prognoses or drug interventions with complex side effects, both introducing unnecessary burdens to patients. To remedy this, non-invasive ultrasound stimulation to the vagus nerve is a novel, low-cost treatment that is showing promise. Although vagus nerve stimulation is already approved for epilepsy and other conditions, it requires regular maintenance. In contrast, studies using non-invasive ultrasound stimulation have shown preliminary positive results in affecting vagal activity with minimal drawbacks. This review covers a variety of studies investigating the effects of ultrasound stimulation on the vagus nerve. With rising levels of anxiety with each generation, there is a pressing need for more innovative and diverse treatments with fewer costs and more benefits. [ABSTRACT FROM AUTHOR]

Extensive research has been conducted on postpartum depression (PPD) over the past century, and yet no definitive answer regarding its etiopathogenesis, risk factors, genetic predilection, and treatment has been found. The few preclinical and clinical studies propose that maternal brain adaptations to the endocrinological, immunological, and behavioral changes and external sociodemographic risk factors in the perinatal period make women more vulnerable to anxiety and depression. Irrespective of the cause, a dilemma exists regarding the type of help to provide postpartum mothers. With very few treatment options at our disposal, deciding between psychotherapy, pharmacological, and non‐pharmacological therapy on a case‐by‐case basis is unproductive because in developing countries infrastructure is limited and the availability of medications, especially for psychiatric illnesses, is still evolving. Hence, regardless of psychotherapy, antidepressants remain the first line of treatment with selective serotonin reuptake inhibitors (SSRIs); sertraline has the best efficacy and safety profile in breastfeeding women. As endocrine factors play a significant role in etiopathogenesis, hormonal therapy with oxytocin has been shown to be efficacious, and studies investigating the role of testosterone in treating PPD are also under way. In 2019, the US Food and Drug Administration (FDA) approved the first and only drug for the sole purpose of treating PPD, brexanolone. Zuranolone, a drug recently approved by the FDA, has a similar mechanism of action to brexanolone. For breastfeeding mothers reluctant to use pharmacotherapy, somatic therapy has been studied, including bright light therapy, vagal nerve stimulation, and newer noninvasive interventions. This article encompasses a short note on PPD, including its etiopathogenesis and clinical characteristics, and recapitulates the various available and evolving pharmacological and nonpharmacological therapies. [ABSTRACT FROM AUTHOR]

Introduction: Vagal nerve stimulation (VNS) is used as an alternative treatment in drug-resistant epilepsy patients. Effects of VNS on the cardiac autonomic system are controversial. In this study, we aimed to investigate the relationship between VNS parameters and heart rate variability (HRV) in epilepsy patients who underwent VNS treatment. Methods: Our study included 31 patients who underwent VNS for drug-resistant epilepsy. Patients were divided into groups according to response to VNS and VNS parameters. All patients underwent 24-h Holter ECG. Results: The mean age of 31 VNS-treated epilepsy patients included in the study was 33.87 ± 7.6 years. When patients were grouped according to VNS response, 25 patients were in the VNS responder group and six patients were in the VNS-nonresponder group. When comparing Holter parameters in the VNS responder and non-responder groups, the median HF was significantly lower in the VNS responder group. VNS duration and signal frequency had a positive effect on LF/HF, while output and off time had a negative effect on LF/HF. When ROC analysis was performed to determine the cut-off values of the parameters for the VNS-responsive state, the AUC value of the HF parameter was 0.780, which was statistically significant. The cut-off value to distinguish response to VNS was 156.9. Conclusion: In conclusion, the effects of VNS parameters on HRV parameters are quite complex. However, the conclusion is that VNS is a neuromodulation method that affects the autonomic system in a complex way. Different levels of VNS parameters may also contribute to this effect. Furthermore, HRV parameters can be used as biomarkers to predict the patient population that may benefit from VNS. [ABSTRACT FROM AUTHOR]

Objective: To observe the effects of transcutaneous auricular vagus nerve stimulation (taVNS) matched with rehabilitation training on upper limb function in children with spastic hemiplegic cerebral palsy. Method: A total of 50 children with spastic hemiplegic cerebral palsy were randomly divided into treatment group (n=25) and control group (n=25). The treatment group received conventional rehabilitation training combined with taVNS, while the control group received conventional rehabilitation training combined with shamtaVNS. The upper limb flexor muscle tension and upper limb function of the two groups were analyzed by the modified Ashworth scale (MAS), Carroll Upper Extremities Functional Test (UEFT), Peabody Developmental Motor Scales-Fine Motor (PDMS-FM) and Function Independence Measure for Children (WeeFIM) before and after 12 weeks of treatment respectively. In addition, any adverse reactions that occurred during the treatment process was closely monitored and recorded. Result: A total of 5 subjects dropped out, including 3 subjects in the treatment group and 2 subjects in the control group. After treatment, there was no significant difference in MAS classification of hemiplegic side in the two groups (P＞0.05), and there was no significant difference between the treatment group and the control group (P=0.065). However, both groups showed significant improvements in UEFT score, PDMS- FM and WeeFIM scores compared to before treatment (P＜0.05), with the treatment group scoring better than the control group (P＜0.05). Conclusion: Conventional rehabilitation training combined with taVNS can effectively improve the affected upper limb motor function in children with spastic hemiplegic cerebral palsy, without significant adverse effects. [ABSTRACT FROM AUTHOR]

Receptive language deficits and aberrant auditory processing are often observed in individuals with autism spectrum disorders (ASD). Symptoms associated with ASD are observed in rodents prenatally exposed to valproic acid (VPA), including deficits in speech sound discrimination ability. These perceptual difficulties are accompanied by changes in neural activity patterns. In both cortical and subcortical levels of the auditory pathway, VPA-exposed rats have impaired responses to speech sounds. Developing a method to improve these neural deficits throughout the auditory pathway is necessary. The purpose of this study was to investigate the ability of vagus nerve stimulation (VNS) paired with sounds to restore degraded inferior colliculus (IC) responses in VPA-exposed rats. VNS paired with the speech sound "dad" was presented to a group of VPA-exposed rats 300 times per day for 20 days. Another group of VPA-exposed rats were presented with VNS paired with multiple tone frequencies for 20 days. The IC responses were recorded from 19 saline-exposed control rats and 18 VPA-exposed with no VNS, 8 VNS-speech paired VPA-exposed, and 7 VNS-tone paired VPA-exposed female and male rats. Pairing VNS with tones increased the IC response strength to speech sounds by 44% compared to VPA-exposed rats alone. Contrarily, VNS-speech pairing significantly decreased the IC response to speech compared with VPA-exposed rats by 5%. The present research indicates that pairing VNS with tones improved sound processing in rats exposed to VPA and suggests that auditory processing can be improved through targeted plasticity. NEW & NOTEWORTHY: Pairing vagus nerve stimulation (VNS) with sounds has improved auditory processing in the auditory cortex of normal-hearing rats and autism models of rats. This study tests the ability of VNS-sound pairing to restore auditory processing in the inferior colliculus (IC) of valproic acid (VPA)-exposed rats. Pairing VNS with tones significantly reversed the degraded sound processing in the IC in VPA-exposed rats. The findings provide evidence that auditory processing in autism rat models can be improved through VNS. [ABSTRACT FROM AUTHOR]

Purpose: To assess responsive neurostimulation (RNS) efficacy in pediatric patients with drug-resistant epilepsy, comparing response (≥ 50% reduction in seizure frequency) rates between patients with two or fewer seizure foci and those with multifocal or generalized epilepsy. This study seeks to address the gap in knowledge regarding RNS effectiveness in pediatric populations. Methods: A systematic review and meta-analysis included data from PubMed, Embase, and Web of Science through November 2023, including 17 retrospective studies and a case series of 24 patients from our practice for a total of 105 aggregated patients. The inclusion criteria of patients were age ≤ 18 and diagnosis of DRE. Exclusion criteria were nonhuman subjects and cases where RNS was not utilized to treat DRE. Study inclusion criteria were detailing the use of RNS and comparing patients with ≤ 2 foci with other focalities. Study exclusion criteria were failure to specify RNS lead placement or type of epilepsy. The risk of bias was assessed using the ROBINS-I tool for all non-randomized studies. Effect sizes and variances were aggregated to provide a comprehensive measure of RNS efficacy, and heterogeneity among the studies was assessed using I2 statistics and Cochran's Q test to evaluate the consistency of the findings. Statistical analyses were conducted using IBM SPSS. We analyzed demographics, epilepsy history, treatment outcomes, and RNS details using descriptive and inferential statistics, including Wilcoxon-Mann–Whitney, Fisher's exact, and chi-squared tests. This systematic review was not registered. Results: Seventeen retrospective studies and a single-institution case series, encompassing 105 pediatric patients, were analyzed. Effect sizes and confidence intervals were calculated to quantify treatment effects. Analyses revealed that RNS reduces seizure frequency across a spectrum of pediatric epilepsy syndromes, irrespective of the seizures' focal, multifocal, or generalized origins. The effectiveness of RNS was not influenced by the patient's sex, age at epilepsy onset, or presence of neurological and psychiatric comorbidities. Prior vagus nerve stimulation surgery and the presence of an epileptic syndrome were factors associated with a lower likelihood of near-complete seizure remission with RNS, underscoring the complexities of treating patients with generalized epilepsies or previous interventional failures. The necessity of further research into individualized surgical strategies for patients was underscored by the mixed results of comparisons of electrode characteristics with responder rates. Limitations of our study include its reliance on retrospective studies, which introduces potential bias and limits the ability to infer causality. Discussion: RNS is a safe and effective treatment in pediatric patients with DRE across demographic, comorbidity, and focality variability. FDA age and focality restrictions, along with patient and physician hesitancy, may be limiting the potential for effective treatment of pediatric DRE with RNS. Prospective randomized trials are recommended to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: To consider the possible role of the vagus nerve (VN) in the pathophysiology of sleep bruxism (SB) and introduce a multimodal protocol of transcutaneous auricular stimulation of the VN in the treatment of SB patients. Methods: Ten patients with SB underwent four sessions of electric transcutaneous auricular vagus nerve stimulation (ta-VNS) in specific auricular areas. The patients were advised to manually stimulate the same areas between sessions. Masticatory muscle activity and sleep parameters were measured by a polysomnography (PSG) before and after the treatment. Heart rate variability (HRV) parameters were measured during each stimulation. Results: PSG analysis revealed a statistically significant reduction in tonic SB index and tonic contraction time. HRV parameters showed a statistically significant increase in mean values of the vagal tone after each session of stimulation. No side effect was reported. Conclusion: The stimulation of the VN might have a role in the treatment of SB. [ABSTRACT FROM AUTHOR]

Increased sympathetic and reduced parasympathetic nerve activity is associated with disease progression and poor outcomes in patients with chronic heart failure. The demonstration that markers of autonomic imbalance and vagal dysfunction, such as reduced heart rate variability and baroreflex sensitivity, hold prognostic value in patients with chronic heart failure despite modern therapies encourages the research for neuromodulation strategies targeting the vagus nerve. However, the approaches tested so far have yielded inconclusive results. This review aims to summarize the current knowledge about the role of the parasympathetic nervous system in chronic heart failure, describing the pathophysiological background, the methods of assessment, and the rationale, limits, and future perspectives of parasympathetic stimulation either by drugs or bioelectronic devices. [ABSTRACT FROM AUTHOR]

Background: Contrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms. Results: mVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb). Conclusions: In summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects. [ABSTRACT FROM AUTHOR]

Gouty inflammation, caused by uric acid crystal deposition, primarily affects tissues around the toe joints and triggers potent inflammatory responses. Current treatments focus on alleviating inflammation and pain using pharmaceutical agents, which can lead to side effects and complications. This has generated interest in non-pharmacological interventions, such as non-invasive vagus nerve stimulation (VNS). In this study, we explored the anti-inflammatory mechanisms of transcutaneous auricular vagus nerve stimulation (taVNS) in a mouse model of acute gout. Gouty inflammation was induced by injecting monosodium urate (MSU) crystals into the ankle joints of BALB/c mice. The effects of taVNS on the expression of inflammatory cytokines and chemokines in the ankle joint tissue were assessed using real-time quantitative PCR (qPCR), western blotting, histological assessments (H&E staining), and immunohistochemistry (IHC). The role of α7 nicotinic acetylcholine receptors (α7nAChR) was also evaluated by signal blocking. Our findings revealed that MSU significantly elevated gout-associated inflammatory cascades and mediators in the ankle joint. Notably, taVNS at 200 µA and 25 Hz effectively reduced these inflammatory responses, decreasing neutrophil infiltration and chemoattraction within the tissue. taVNS showed significant anti-inflammatory properties by suppressing neutrophil activity, offering a novel therapeutic approach for gout beyond conventional pharmacological methods. Additionally, taVNS holds potential for managing various chronic joint diseases. These results highlight taVNS as a promising non-pharmacological therapy for chronic inflammation. [ABSTRACT FROM AUTHOR]

The autonomic regulation of the pulmonary vasculature has been under‐appreciated despite the presence of sympathetic and parasympathetic neural innervation and adrenergic and cholinergic receptors on pulmonary vessels. Recent clinical trials targeting this innervation have demonstrated promising effects in pulmonary hypertension, and in this context of reignited interest, we review autonomic pulmonary vascular regulation, its integration with other pulmonary vascular regulatory mechanisms, systemic homeostatic reflexes and their clinical relevance in pulmonary hypertension. The sympathetic and parasympathetic nervous systems can affect pulmonary vascular tone and pulmonary vascular stiffness. Local afferents in the pulmonary vasculature are activated by elevations in pressure and distension and lead to distinct pulmonary baroreflex responses, including pulmonary vasoconstriction, increased sympathetic outflow, systemic vasoconstriction and increased respiratory drive. Autonomic pulmonary vascular control interacts with, and potentially makes a functional contribution to, systemic homeostatic reflexes, such as the arterial baroreflex. New experimental therapeutic applications, including pulmonary artery denervation, pharmacological cholinergic potentiation, vagal nerve stimulation and carotid baroreflex stimulation, have shown some promise in the treatment of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

Targeted plasticity therapy (TPT) utilizes vagus nerve stimulation (VNS) to promote improvements in function following neurological injury and disease. During TPT, a brief burst of VNS induces neuromodulator release, which when paired with relevant behavioral events can influence functionally relevant neuroplasticity. Functional improvements following TPT are therefore in part mediated by neuromodulator signaling. Unfortunately, comorbidities associated with neurological disease often result in altered cognitive states that can influence neuromodulator signaling, potentially impeding neuroplasticity induced by TPT. Aside from altered cognitive states, cardiorespiratory rhythms also affect neuromodulator signaling, due to the vagus nerve’s role in relaying visceral sensory information from the cardiovascular and respiratory systems. Moreover, precise VNS delivery during specific periods of the cardiorespiratory rhythms may further improve TPT. Ultimately, understanding the impact of patient-specific states on neuromodulator signaling may likely facilitate optimized VNS delivery, paving the way for personalized neuromodulation during TPT. Overall, this review explores challenges and considerations for developing advanced TPT paradigms, focusing on altered cognitive states and cardiorespiratory rhythms. We specifically discuss the possible impact of these cognitive states and autonomic rhythms on neuromodulator signaling and subsequent neuroplasticity. Altered cognitive states (arousal deficits or pain) could affect VNS intensity, while cardiorespiratory rhythmsmay further inform optimized timing of VNS. We propose that understanding these interactions will lead to the development of personalized state dependent VNS paradigms for TPT. [ABSTRACT FROM AUTHOR]

Social cognitive deficits and social behavior impairments are common in major depressive disorder (MDD) and affect the quality of life and recovery of patients. This review summarizes the impact of standard and novel treatments on social functioning in MDD and highlights the potential of combining different approaches to enhance their effectiveness. Standard treatments, such as antidepressants, psychotherapies, and brain stimulation, have shown mixed results in improving social functioning, with some limitations and side effects. Newer treatments, such as intranasal oxytocin, mindfulness-based cognitive therapy, and psychedelic-assisted psychotherapy, have demonstrated positive effects on social cognition and behavior by modulating self-referential processing, empathy, and emotion regulation and through enhancement of neuroplasticity. Animal models have provided insights into the neurobiological mechanisms underlying these treatments, such as the role of neuroplasticity. Future research should explore the synergistic effects of combining different treatments and investigate the long-term outcomes and individual differences in response to these promising interventions. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) is the subject of exploration as an adjunct treatment for neurological disorders such as epilepsy, chronic migraine, pain, and depression. A non‐invasive form of VNS is transcutaneous auricular VNS (taVNS). Combining animal models and positron emission tomography (PET) may lead to a better understanding of the elusive mechanisms of taVNS. We evaluated the acute effect of electrical stimulation of the left vagus nerve via the ear on brain synaptic vesicle glycoprotein 2A (SV2A) as a measure of presynaptic density and glucose metabolism in naïve rats. Female Sprague–Dawley rats were imaged with [11C]UCB‐J (n = 11) or [18F]fluorodeoxyglucose ([18F]FDG) PET (n = 13) on two separate days, (1) at baseline, and (2) after acute unilateral left taVNS or sham stimulation (30 min). We calculated the regional volume of distribution (VT) for [11C]UCB‐J and standard uptake values (SUV) for [18F]FDG. We observed regional reductions of [11C]UCB‐J binding in response to taVNS ranging from 36% to 59%. The changes in taVNS compared to baseline were significantly larger than those induced by sham stimulation. The differences were observed bilaterally in the frontal cortex, striatum, and midbrain. The [18F]FDG PET uptake remained unchanged following acute taVNS or sham stimulation compared to baseline values. This proof‐of‐concept study shows for the first time that acute taVNS for 30 min can modulate in vivo synaptic SV2A density in cortical and subcortical regions of healthy rats. Preclinical disease models and PET ligands of different targets can be a powerful combination to assess the therapeutic potential of taVNS. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aims to comprehensively analyze the efficacy and underlying mechanisms of vagus nerve stimulation (VNS) in enhancing cognitive functions and its therapeutic potential for various cognitive impairments. The review focuses on the impact of VNS on emotional processing, executive functions, learning, memory, and its clinical applications in conditions such as epilepsy, depression, Alzheimer's disease, and other neurological disorders. Methods: A systematic search of electronic databases (PubMed, Scopus, Web of Science) was conducted using the keywords "vagus nerve stimulation," "cognitive enhancement," "emotional processing," "executive function," "learning and memory," "epilepsy," "depression," "Alzheimer's disease," "neurological disorders," "attention-deficit/hyperactivity disorder," "sleep disorders," and "long COVID." The inclusion criteria encompassed controlled trials, longitudinal studies, and meta-analyses published in English between 2000 and July 2024. Results: A comprehensive review of 100 articles highlighted the cognitive effects of Vagus Nerve Stimulation (VNS). Studies show that VNS, especially through transcutaneous auricular VNS (taVNS), enhances emotional recognition, particularly for facial expressions, and improves selective attention under high cognitive demands. Additionally, VNS enhances learning and memory, including associative memory and spatial working memory tasks. In clinical applications, VNS exhibits promising benefits for improving cognitive functions in treatment-resistant epilepsy, depression, and Alzheimer's disease. Conclusion: VNS represents a promising therapeutic approach for enhancing cognitive function across diverse patient populations. The reviewed evidence highlights its efficacy in modulating cognitive domains in healthy individuals and improving cognition in neurological conditions. However, the comparative effectiveness of different VNS modalities and the differential effects of online versus offline VNS on cognitive psychology require further investigation. Future research should focus on optimizing VNS protocols and elucidating specific cognitive domains that benefit most from VNS interventions. This ongoing exploration is essential for maximizing the therapeutic potential of VNS in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Long-term post-stroke cognitive impairment (PSCI) exhibits an accelerated rate of long-term cognitive decline, which can impair communication, limit social engagement, and increase rate of institutional dependence. The aim of this case report is to provide evidence for the potential of home-based transcutaneous auricular vagus nerve stimulation (taVNS) for home-bound patients with severe, long-term PSCI. Methods: A 71-year-old male suffered a stroke two and a half years ago, which imaging reported foci of cerebral infarction visible in the left temporal and parietal lobes. The patient was performed taVNS twice a day for 30 min, 5 times a week for 8 weeks. The patient was evaluated the changes of cognitive function and brain white matter at 4 time points: baseline (t0), 4 weeks without taVNS after baseline (t1), 4 weeks of intervention (t2), and 8 weeks of intervention (t3). The effect of taVNS on white matter changes was visualized by DTI. Results: After 8 weeks of taVNS treatment, the scores of Montreal cognitive assessment improved and the time to complete the shape trails test decreased. The DTI results showed that white matter in bilateral dorsal lateral prefrontal cortex remodeled after taVNS. Conclusion: Eight-week home-based taVNS may be beneficial to long-term PSCI. Further studies of home-based taVNS treating patients with long-term PSCI are needed. [ABSTRACT FROM AUTHOR]

The efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) as a non-invasive method to modulate physiological markers of noradrenergic activity of the Locus Coeruleus (LC), such as pupil dilation, is increasingly more discussed. However, taVNS studies show high heterogeneity of stimulation effects. Therefore, a taVNS setup was established here to test different frequencies (10 Hz and 25 Hz) and intensities (3 mA and 5 mA) during phasic stimulation (3 s) with time-synchronous recording of pupil dilation in younger adults. Specifically, phasic real taVNS and higher intensity led to increased pupil dilation, which is consistent with phasic invasive VNS studies in animals. The results also suggest that the influence of intensity on pupil dilation may be stronger than that of frequency. However, there was an attenuation of taVNS-induced pupil dilation when differences in perception of sensations were considered. Specifically, pupil dilation during phasic stimulation increased with perceived stimulation intensity. The extent to which the effect of taVNS induces pupil dilation and the involvement of sensory perception in the stimulation process are discussed here and require more extensive research. Additionally, it is crucial to strive for comparable stimulation sensations during systematic parameter testing in order to investigate possible effects of phasic taVNS on pupil dilation in more detail. [ABSTRACT FROM AUTHOR]

Migraine is a prevalent neurological disorder, particularly among individuals aged 20–50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Paired associative stimulation (PAS) is a combination of transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). PAS can induce long‐term potentiation (LTP)‐like plasticity in humans, manifested as motor‐evoked potential (MEP) enhancement. We have developed a variant of PAS ("high‐PAS"), which consists of high‐frequency PNS and high‐intensity TMS and targets spinal plasticity and promotes rehabilitation after spinal cord injury (SCI). Vagus nerve stimulation (VNS) promotes LTP‐like plasticity and enhances recovery in SCI and stroke in humans and animals when combined with repetitive motor training. We combined high‐PAS with simultaneous noninvasive transcutaneous auricular VNS (aVNS) to determine if aVNS enhances the extent of PAS‐induced MEP amplitude increase. Sixteen healthy participants were stimulated for 20 min in four different sessions (PAS, PAS + aVNS, PAS + shamVNS, and aVNS) in a randomized single‐blind setup. MEPs were measured before, immediately after, and at 30, 60, and 90 min post‐stimulation. Stimulation protocols with PAS significantly potentiated MEPs (p = 0.005) when compared with aVNS (p = 0.642). Although not significant, MEP enhancement observed after PAS (43.5%) is further increased by aVNS (49.7%) and electrical earlobe stimulation (63.9%). Our aVNS setup failed to significantly enhance the effect of PAS, but sham VNS revealed a trend towards enhanced plasticity. Optimization of auricular VNS stimulation setup is required for possible tests of patients with SCI. [ABSTRACT FROM AUTHOR]

Aim Method Results Conclusion Ileus is characterized by a period of intestinal dysmotility after surgery, leading to vomiting and constipation. In preclinical models, vagus nerve stimulation reduces intestinal inflammation and prevents smooth muscle dysfunction, accelerating the return of gut function. This study explored the feasibility of a definitive trial of non‐invasive vagus nerve stimulation (nVNS) along with an early assessment of efficacy.A multicentre, randomized feasibility trial (IDEAL Stage 2B) of self‐administered nVNS was performed. Patients undergoing colorectal surgery were randomized to nVNS or sham before and after surgery. Feasibility outcomes comprised assessments of recruitment, compliance, blinding and attrition. Clinical outcomes were measures of intestinal function and adverse events. All participants were followed up for 30 days. Interviews with patients and health professionals explored barriers to feasibility and perspectives around implementation.In all, 125 patients were approached about the study and 97 (77.6%) took part. Across all randomized groups, the median compliance to treatment was 19 out of 20 stimulations (interquartile range 17–20). The incidence of adverse events was similar across groups. In this unpowered feasibility study, the time taken for the return of gut function (such as first passage of stool) was similar between nVNS and sham treatments. According to interviews, patients were highly motivated to use the device because it provided them with an opportunity to engage actively in their care. Health professionals were highly driven to tackle the problem of ileus.Powered assessments of clinical efficacy are required to confirm or refute the promise of nVNS, as already demonstrated in preclinical models. This feasibility study concludes that a definitive randomized assessment of the clinical benefits of nVNS is desired and feasible. [ABSTRACT FROM AUTHOR]

Objectives: Non-invasive vagus nerve stimulation (nVNS) is an emerging neuromodulation technique in recent years, which plays a role in nervous system diseases, psychiatric diseases, and autoimmune diseases. However, there is currently no comprehensive analysis of all the literature published in this field. Therefore, in this article, a bibliometric analysis will be conducted on all the literature published in the field of nVNS in the past 20 years. Methods: All articles and reviews published in this field from 2004 to 2023 were extracted from the WOS core database. VOSviewer 1.6.18.0, Scimago Graphica, CiteSpace 6.2.R2, and Excel 2021 were used to analyze the number of publications, participating countries, institutions, authors, references, and research hotspots in this field. Results: A total of 843 articles were included in the bibliometric analysis of nVNS. Over the past 20 years, the number of publications in this field has gradually increased, reaching a peak in 2023. The United States and China ranked top two in terms of publication volume, and institutions from these two countries also ranked high in terms of publication volume, citation count, and collaboration intensity. Rong Peijing is the author with the most publications, while Bashar W Badran is the most cited author. Articles in the field of nVNS were most frequently published in Frontiers in Neuroscience, while Brain Stimulation had the most citations. Currently, research hotspots in nVNS mainly focus on its application in diseases and related mechanisms. Conclusion: We conducted a comprehensive analysis of the field of nVNS, clarifying the previous research directions, which is helpful to expand its indications and promote clinical application. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has identified epilepsy as a significant public health issue that requires urgent attention. Epilepsy is a neurological disorder that affects millions of people worldwide and can lead to social, economic, and health challenges. The WHO emphasizes the need for improved awareness, diagnosis, treatment, and support for individuals with epilepsy. Neurosurgical interventions for epilepsy include removing or altering brain regions that generate seizures or implanting devices to regulate abnormal electrical activity. These interventions have advanced with technologies such as robotic assistance and neuromodulation devices. Neurosurgical treatment can significantly improve the quality of life for patients with drug-resistant epilepsy, even leading to complete seizure freedom. However, there are risks and challenges associated with these interventions, and careful patient selection and support are crucial. The future of epilepsy management may involve advances in neurotechnology, a focus on comorbidities, and continued research and clinical trials. The goal is to empower individuals with epilepsy to lead meaningful lives through personalized medicine, innovative treatments, and compassionate care. [Extracted from the article]

ABSTRACT: Background: Dental care of patients with epilepsy and seizures must be performed by dentists who are familiar with these disorders. Improper training and incapability to manage medical emergencies, including epileptic seizures, may cause thoughtful consequences and legal actions. Therefore, dental students must have a proper knowledge of the disease and its consequences. They should have the ability to provide first-aid measures helping a patient experiencing an epileptic seizure in their clinics. This study aims to evaluate the first-aid knowledge and practices towards patients with epileptic seizures among the dental students in Saudi Arabia. Methods: A cross-sectional study was conducted targeting dental students in Saudi Arabia from 15 September 2022 to 15 December 2022 using convenience sampling. An online questionnaire was sent to the students via social media platforms for data collection. The data analysis was conducted using the Statistical Package for the Social Sciences (SPSS) version 16.0. Results: Of the 499 dental students included, 154 (30.86%) students had ever seen an epileptic patient in the clinics. About 16% of students did not know about performing cardiopulmonary resuscitation (CPR) on patients. The majority (66.5%) would call the ambulance after the patient's seizure stops. About 82% of students prefer to call an ambulance if the patients face difficulty breathing or waking up after the seizure. More than 60% of students were taking precautions before treating an epilepsy patient. About 58.5% of the students were using local anaesthesia for an epilepsy patient. Nearly 41.9% do not have the confidence to treat an epilepsy patient. About 28.0% would swipe the vagus nerve stimulation (VNS) magnet over the left side of the chest. Of 154 students, who had ever seen epileptic patients, the majority (68.8%) refused to treat patients if they observe noncompliance with medication and follow-up among the patients who had any recent illness or seizures (16.2%). Conclusion: The undergraduate dental students had an intermediate knowledge regarding epilepsy and epileptic seizure first aid. However, some students lacked the confidence to deal with the epileptic cases in their clinics. Educational campaigns on epilepsy and first-aid courses targeting dental students are highly recommended. [ABSTRACT FROM AUTHOR]

Introduction: Treatment‐resistant depression (TRD) is a condition in which patients suffering from depression no longer respond to common methods of treatment, such as anti‐depressant medication. Neurosurgical procedures such as ablative surgery, deep brain stimulation, and vagus nerve stimulation have been used in efforts to overcome TRD. Objectives: This review aims to provide an overview of the side effects of neurosurgery performed in clinical studies related to depression. Methods: A literature search was conducted through PubMed, MEDLINE, EMBASE, Ovid, and ClinicalTrials.gov databases. Results: This review selected 10 studies for ablative surgery, 12 for deep brain stimulation, and 10 for vagus nerve stimulation, analyzing their side effect profiles of neurosurgery for TRD. The major side effects of each type of neurosurgery were identified, such as incontinence and confusion for ablative surgery, headaches and increased suicide ideation for deep brain stimulation, and voice hoarseness and dyspnea for vagus nerve stimulation. Conclusion: The review discusses the merits and demerits of neurosurgery as a treatment option for TRD. It also suggests new insights into decreasing the burden of these neurosurgical side effects so that they can be a viable, high‐efficacy treatment method for TRD. [ABSTRACT FROM AUTHOR]