Methods Protoc. 2024 Dec 11;7(6):99. doi: 10.3390/mps7060099.

ABSTRACT

Both the prevalence and mortality of liver cancers continue to rise. Early surgical interventions, including liver transplantation or resection, remain the only curative treatment. Nerves in the periphery influence tumor growth within visceral organs. Emerging cancer neuroscience efforts linked parasympathetic vagus nerves with tumor pathology, underscoring the value of vagal nerve denervation methods within cancer mouse models. Here, we describe a selective hepatic vagotomy that largely maintains non-liver parasympathetic innervation in mice. To address vagal interactions in hepatic tumor pathology, we provide an adapted methodology utilizing an established liver metastatic model. We anticipate that this methodology will expand the burgeoning field of cancer neuroscience, enabling the study of the neuroimmune, neurometabolic, and/or nerve-microbiota interactions shaping liver cancer progression and treatment.

PMID:39728619 | PMC:PMC11677442 | DOI:10.3390/mps7060099

Psychophysiology. 2025 Jan;62(1):e14744. doi: 10.1111/psyp.14744.

ABSTRACT

Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered increasing attention as a safe and effective peripheral neuromodulation technique in various clinical and cognitive neuroscience fields. However, there is ongoing debate about whether the commonly used earlobe control interferes with the objective assessment of taVNS regulatory effects. This study aims to further explore the regulatory effects of taVNS and earlobe stimulation (ES) on alertness levels and physiological indicators following 24 h of sleep deprivation (SD), based on previous findings that both taVNS and ES showed significant positive effects. The goal is to evaluate whether ES can serve as a neutral sham condition. Using a within-subject randomized experimental design involving 56 participants, we assessed alertness, heart rate variability (HRV), and salivary alpha-amylase (sAA) levels in the morning of the first day. After 24 h of SD and 30 min of either taVNS or ES intervention, these indicators were re-evaluated, and the changes in both groups were analyzed. The results indicated that both taVNS and ES improved alertness levels following SD. However, taVNS significantly increased sAA levels, indicating activation of the LC-NE system, whereas ES significantly increased HR and reduced HRV, promoting sympathetic nervous activity. Additionally, the regulatory effect of taVNS on the alertness showed a higher correlation with SD impairment. Although taVNS and ES may involve different and separable neuromodulation mechanisms, both can enhance alertness following SD. Future studies should carefully consider the potential regulatory effects of ES when using it as a sham condition in taVNS research.

PMID:39727264 | DOI:10.1111/psyp.14744

J Affect Disord. 2024 Dec 23:S0165-0327(24)02060-3. doi: 10.1016/j.jad.2024.12.072. Online ahead of print.

ABSTRACT

BACKGROUND: Suicide attempts are a major concern in major depressive disorder (MDD), especially for those with multiple prior unsuccessful treatment trials. This report compares baseline demographic, clinical features, and treatment history of participants with marked treatment-resistant, nonpsychotic MDD based on lifetime history of suicide attempt (SA vs NSA).

METHODS: RECOVER is a randomized, sham-controlled trial of vagus nerve stimulation and the largest such trial of a psychiatric neuromodulation intervention. Baseline data were analyzed. Univariate analyses (SA vs NSA) and logistic regression with backward selection (variables with univariate p < 0.1) were performed.

RESULTS: SA group (N = 196) was more likely than NSA group (N = 297) to be female (72.4 % vs 61.6 %), <65 years of age (73.5 % vs 61.6 %), have earlier onset of depressive symptoms (mean, 19.1 vs 22.5 years), earlier diagnosis of MDD (mean, 25.0 vs 29.2 years), higher percentage of lifetime in depressive episodes (mean, 56.0 % vs 51.0 %), more failed antidepressants (mean, 15.0 vs 12.1), and greater lifetime use of electroconvulsive therapy (ECT; 55.1 % vs 40.1 %). Female sex, age at MDD diagnosis, number of failed antidepressants, number of psychiatric hospitalizations, and baseline suicide score retained association with logistic regression analysis.

LIMITATIONS: Information on medical morbidity of suicide attempts was not collected and timing of suicide attempts relative to treatment exposures was unknown.

CONCLUSIONS: For marked treatment-resistant MDD, those with prior suicide attempts have more complex course of illness with earlier onset of depressive symptoms, earlier diagnosis of MDD, more lifetime spent in depressive illness, more failed antidepressant medication trials, and greater use of ECT.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03887715.

PMID:39722333 | DOI:10.1016/j.jad.2024.12.072

Physiol Behav. 2024 Dec 24;291:114793. doi: 10.1016/j.physbeh.2024.114793. Online ahead of print.

ABSTRACT

Over 10 % of the US population are prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to combat obesity. Although they decrease cravings for foods, their influence on chemosensory function is unknown. We employed state-of-the-art quantitative taste and smell tests to address this issue. The 53-item Waterless Empirical Taste Test (WETT®) and the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) were completed by 46 persons taking GLP-1 RAs and 46 controls matched on age, sex, smoking behavior, and COVID-19 infection histories. Data were analyzed using analyses of variance. The WETT® scores were significantly diminished in the GLP-1 RA group relative to controls [total means (95 % CIs) = 28.61 (25.66,31.56) and 40.63 (38.35,42.91), p < 0.001, η² = 0.37]. Eighty five percent of the GLP-1 subjects scored worse than their individually matched controls. All 5 WETT® subtest scores were similarly affected (ps < 0.001). Smell function, although slightly decreased on average, was not significantly impacted (p = 0.076). Women outperformed men on all tests. Remarkably, UPSIT® and WETT® scores were higher, i.e., better, in those reporting nausea, diarrhoea, and other GLP-1-related side effects. This study demonstrates, for the first time, that GLP-1 RAs alter the function of a major sensory system, significantly depressing the perception of all five basic taste qualities. The physiologic basis of this effect is unknown but may involve GLP-1 receptors in the brainstem and afferent taste pathways, as well as vagus nerve-related processes.

PMID:39722367 | DOI:10.1016/j.physbeh.2024.114793

J Physiol. 2024 Dec 25. doi: 10.1113/JP287596. Online ahead of print.

ABSTRACT

Loss of cardiac physiological function following myocardial infarction (MI) is accompanied by neural adaptations in the baroreflex that are compensatory in the short term, but then become associated with long-term disease progression. One marker of these adaptations is decreased baroreflex sensitivity, a strong predictor of post-MI mortality. The relative contributions of cardiac remodelling and neural adaptation in the sensory, central brainstem and peripheral ganglionic loci to baroreflex sensitivity changes remain underexplored. We used a computational model-based approach that accounts for the short-term dynamics of closed-loop human cardiac control to integrate disparate experimental studies on neural adaptation following MI into a unified quantitative framework. We developed an ensemble of 59 distinct model parameterizations that account for the clinically observed heterogeneity of cardiac control in healthy individuals. We simulated an in silico cohort of 35,400 patients with MI, corresponding to six scenarios of one or more loci of neural adaptation coupled with cardiac remodelling. We evaluated the range of MI-induced shifts in arterial pressure, heart rate and baroreflex curve responses. Our results show that adaptation in any single neural locus coupled with cardiac remodelling is sufficient to account for the MI-induced haemodynamic and autonomic changes observed experimentally. Of the adaptation pathways, we found that individuals with central or peripheral vagal efferent adaptation and preserved baroreceptor gain could maintain high baroreflex sensitivity after ischaemic injury. These results suggest that there are a multitude of adaptive pathways for tuning the baroreflex circuit to shift cardiac control physiology, potentially explaining patient heterogeneity post-MI. KEY POINTS: Baroreflex sensitivity is a strong indicator of post-myocardial ischaemia survival and is variable among individuals. We fine-tuned a computational model ensemble based on physiological observations to develop an in silico patient cohort consistent with the range of baroreflex responses observed experimentally. Simulation and analysis of the in silico cohort show that individuals with a functional afferent pathway and the ability to adapt along the vagal efferent pathway can maintain baroreflex sensitivity post-cardiac ischaemia.

PMID:39722577 | DOI:10.1113/JP287596

Neuropsychiatr Dis Treat. 2024 Dec 21;20:2593-2601. doi: 10.2147/NDT.S492043. eCollection 2024.

ABSTRACT

Patients with stroke would have persistent functional deficits despite undergoing physiotherapy and rehabilitation training. Recently, vagus nerve stimulation (VNS), a newly emerging neuroregulatory technique, has been shown to improve motor dysfunction after stroke. Evidence from clinical and preclinical studies has proven the safety, feasibility, and efficacy of invasive and noninvasive VNS. It has been reported that the positive effect may be related to anti-inflammatory effects, mediating neuroplasticity, increasing blood-brain barrier integrity, promoting angiogenesis and reducing spreading depolarization. However, the underlying mechanism remains poorly understood. In this review, we have summarized the potential molecular mechanisms by which VNS promotes stroke prognosis. We believe that VNS combined with upper-extremity rehabilitation can improve impairment and function among moderately to severely impaired stroke survivors. The applications and further exploration are discussed to provide new insights into this novel therapeutic technique.

PMID:39723115 | PMC:PMC11669332 | DOI:10.2147/NDT.S492043

Front Neurosci. 2024 Dec 11;18:1510658. doi: 10.3389/fnins.2024.1510658. eCollection 2024.

ABSTRACT

BACKGROUND: Vagus nerve stimulation (VNS) has emerged as a promising therapeutic approach for stroke treatment, drawing significant attention due to its potential benefits. However, despite this growing interest, a systematic bibliometric analysis of the research landscape is yet to be conducted.

METHODS: We performed a comprehensive search of the Web of Science Core Collection (WoSCC) database for literature published between January 1, 2005, and August 31, 2024. CiteSpace and the Bibliometrix package in R software were used to generate knowledge maps and conduct a bibliometric analysis. This analysis focused on publication output, geographic distribution, institutional involvement, author and co-cited author networks, journal and co-cited journal relationships, co-cited references, and keyword trends.

RESULTS: During the study period, 316 publications on VNS in stroke were identified, authored by 1,631 researchers from 1,124 institutions across 172 countries or regions. The number of publications showed steady growth, with the United States of America (USA) leading as the primary contributor. The University of Texas System emerged as the most active research institution. Frontiers in Neuroscience published the highest number of articles, while Stroke had the most citations. Professor Michael P. Kilgard authored the largest number of papers and was also the most frequently cited researcher. The main research trends focus on investigating VNS mechanisms via animal models and exploring its application in improving post-stroke sensorimotor function in the upper limbs. Moreover, VNS is showing promise in enhancing non-motor functions, such as swallowing, speech, and cognition, while addressing complications like post-stroke insomnia, depression, and disruptions in gut microbiota.

CONCLUSION: This bibliometric study offers a comprehensive overview of the research landscape and emerging trends in VNS for stroke rehabilitation, providing a solid foundation and reference point for future research directions in this field.

PMID:39723424 | PMC:PMC11668697 | DOI:10.3389/fnins.2024.1510658

Front Neurol. 2024 Dec 10;15:1480819. doi: 10.3389/fneur.2024.1480819. eCollection 2024.

ABSTRACT

OBJECTIVE: This study aims to evaluate the efficacy and safety of deep brain stimulation (DBS) of the medial pulvinar nucleus (PuM) in reducing seizure frequency and addressing comorbidities in patients with drug and vagal nerve-resistant focal epilepsy.

METHODS: This is an open-label prospective treatment trial with a planned enrollment of 12 patients suffering from medically refractory epilepsy (Clinical trial gov NCT04692701), for which the interim 12-month post-implantation results for the first 6 patients are being reported. Inclusion criteria were focal epilepsy not suitable for or after failed surgical intervention and previous failure of neurostimulation therapies (vagus nerve stimulation or anterior thalamic nucleus DBS). Evaluations included seizure diaries, neuropsychological assessments, and scales for depression, anxiety, quality of life, and seizure severity. PuM DBS was performed using ROSA robotic assistance, with follow-ups every 3 months for 1 year.

RESULTS: Out of six patients, five completed 1-year follow-up (one patient died prematurely). A non-significant trend toward seizure reduction was observed at 6 months, becoming more pronounced at 1 year (mean reduction: 45%; responders: 2/5). Seizure severity significantly improved (p = 0.02), with a reduction in the NHS3 scale scores. Quality of life improved significantly at 1 year (p = 0.03). Psychiatric assessments indicated a non-significant trend toward improvement in depression (mean improvement: 26%) and anxiety (mean improvement: 20%) scores. Neuropsychological testing showed stable or improved cognitive performance in three out of five patients. Adverse events included one case of cerebral hemorrhage, one infection leading to device removal, and one possible SUDEP.

SIGNIFICANCE: Preliminary results suggest that PuM DBS may offer a promising therapeutic option for reducing seizure severity and improving quality of life and cognitive functions in patients with drug-resistant epilepsy. Despite the small sample size and the presence of serious adverse events, the findings warrant further investigation with larger cohorts to confirm these trends and optimize the treatment protocol.

PMID:39719976 | PMC:PMC11667892 | DOI:10.3389/fneur.2024.1480819

Front Cardiovasc Med. 2024 Dec 10;11:1517990. doi: 10.3389/fcvm.2024.1517990. eCollection 2024.

ABSTRACT

BACKGROUND: Pregnancy increases the risk of supraventricular tachycardia (SVT) due to physiological changes. This study reviews the management of SVT in pregnant patients in the emergency department (ED).

METHODS: We retrospectively analyzed 15 pregnant patients with SVT treated at Shenzhen Second People’s Hospital ED from 2015 to 2023. Treatments included vagal nerve stimulation, pharmacotherapy, esophageal pacing, cardioversion, and radiofrequency ablation.

RESULTS: The average patient age was 30.3 years. All presented with palpitations, and none had hemodynamic instability. Treatment success varied: 3 patients reverted spontaneously, 5 responded to vagal stimulation, and 4 to esophageal pacing. One required verapamil, and another responded to labetalol after failing vagal and pacing treatments.

CONCLUSION: When managing SVT during pregnancy, it is important to consider the patient’s stability, the stage of pregnancy, and the safety of medications. For unstable patients, electrical cardioversion is the preferred option; for stable patients, vagus nerve stimulation (VNS) or other alternative treatments, such as adenosine, should be considered.

PMID:39720210 | PMC:PMC11666441 | DOI:10.3389/fcvm.2024.1517990

Clin EEG Neurosci. 2024 Dec 24:15500594241308594. doi: 10.1177/15500594241308594. Online ahead of print.

ABSTRACT

Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers’ values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS – 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.

PMID:39716930 | DOI:10.1177/15500594241308594