Neurotherapeutics. 2024 Jul 4:e00422. doi: 10.1016/j.neurot.2024.e00422. Online ahead of print.

ABSTRACT

The mechanisms of action of Vagus Nerve Stimulation (VNS) and the biological prerequisites to respond to the treatment are currently under investigation. It is hypothesized that thalamocortical tracts play a central role in the antiseizure effects of VNS by disrupting the genesis of pathological activity in the brain. This pilot study explored whether in vivo microstructural features of thalamocortical tracts may differentiate Drug-Resistant Epilepsy (DRE) patients responding and not responding to VNS treatment. Eighteen patients with DRE (37.11 ​± ​10.13 years, 10 females), including 11 responders or partial responders and 7 non-responders to VNS, were recruited for this high-gradient multi-shell diffusion Magnetic Resonance Imaging (MRI) study. Using Diffusion Tensor Imaging (DTI) and multi-compartment models – Neurite Orientation Dispersion and Density Imaging (NODDI) and Microstructure Fingerprinting (MF), we extracted microstructural features in 12 subsegments of thalamocortical tracts. These characteristics were compared between responders/partial responders and non-responders. Subsequently, a Support Vector Machine (SVM) classifier was built, incorporating microstructural features and 12 clinical covariates (including age, sex, duration of VNS therapy, number of antiseizure medications, benzodiazepine intake, epilepsy duration, epilepsy onset age, epilepsy type – focal or generalized, presence of an epileptic syndrome – no syndrome or Lennox-Gastaut syndrome, etiology of epilepsy – structural, genetic, viral, or unknown, history of brain surgery, and presence of a brain lesion detected on structural MRI images). Multiple diffusion metrics consistently demonstrated significantly higher white matter fiber integrity in patients with a better response to VNS (p_FDR < 0.05) in different subsegments of thalamocortical tracts. The SVM model achieved a classification accuracy of 94.12%. The inclusion of clinical covariates did not improve the classification performance. The results suggest that the structural integrity of thalamocortical tracts may be linked to therapeutic effectiveness of VNS. This study reveals the great potential of diffusion MRI in improving our understanding of the biological factors associated with the response to VNS therapy.

PMID:38964949 | DOI:10.1016/j.neurot.2024.e00422

IEEE J Biomed Health Inform. 2024 Jul 4;PP. doi: 10.1109/JBHI.2024.3423019. Online ahead of print.

ABSTRACT

Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging neuro modulation technology that has been reported to be beneficial in the treatment of diseases by several studies, but its exact mechanism of action is still unclear. It has been demonstrated that ta VNS can influence interoceptive signals. Notably, the processing of interoceptive signals is directly related to many diseases, such as depression, anxiety, and insomnia. The insula and the medial prefrontal cortex (MPFC) communicate during the bottom-up transmission of taVNS-induced signals, and both play a role in interoceptive signal processing. By focusing on the insula and MPFC, our research pioneers detail the potential interactions between interoceptive signal processing and the neuromodulation effects of taVNS, providing novel insights in to the neurobiological mechanisms of taVNS. Two functional connectivity (FC) analyses (region of interest-based and seed-based) were used in this study. We observed that negative connectivity between the insula and the MPFC was significantly weakened following taVNS, while there were no statistical changes in the sham group. Our findings elucidate potential mechanisms linking vagal activity with intrinsic FC among specific brain regions and networks. Specifically, our results indicate that taVNS may enhance the ability to flexibly balance interoceptive awareness and cognitive experiences by modulating the FC between the insula and MPFC. The modulation effects may impact body-brain interactions, suggesting the mechanism of taVNS in therapeutic applications.

PMID:38963749 | DOI:10.1109/JBHI.2024.3423019

Exp Brain Res. 2024 Jul 4. doi: 10.1007/s00221-024-06876-x. Online ahead of print.

ABSTRACT

Bilateral transcutaneous auricular vagus nerve stimulation (taVNS) – a non-invasive neuromodulation technique – has been investigated as a safe and feasible technique to treat many neuropsychiatric conditions. such as epilepsy, depression, anxiety, and chronic pain. Our aim is to investigate the effect of taVNS on neurophysiological processes during emotional and Go/No-Go tasks, and changes in frontal alpha asymmetry. We performed a randomized, double-blind, sham-controlled trial with 44 healthy individuals who were allocated into two groups (the active taVNS group and the sham taVNS group). Subjects received one session of taVNS (active or sham) for 60 min. QEEG was recorded before and after the interventions, and the subjects were assessed while exposed to emotional conditions with sad and happy facial expressions, followed by a Go/No-Go trial. The results demonstrated a significant increase in N2 amplitude in the No-Go condition for the active taVNS post-intervention compared to the sham taVNS after adjusting by handedness, mood, and fatigue levels (p = 0.046), significantly reduced ERD during sad conditions after treatment (p = 0.037), and increased frontal alpha asymmetry towards the right frontal hemisphere during the emotional task condition (p = 0.046). Finally, we observed an interesting neural signature in this study that suggests a bottom-up modulation from brainstem/subcortical to cortical areas as characterized by improved lateralization of alpha oscillations towards the frontal right hemisphere, and changes in ERP during emotional and Go/No-Go tasks that suggests a better subcortical response to the tasks. Such bottom-up effects may mediate some of the clinical effects of taVNS.

PMID:38963558 | DOI:10.1007/s00221-024-06876-x

Front Neurol. 2024 Jun 19;15:1401982. doi: 10.3389/fneur.2024.1401982. eCollection 2024.

ABSTRACT

INTRODUCTION: Swallowing impairment is a crucial issue that can lead to aspiration, pneumonia, and malnutrition. Animal models are useful to reveal pathophysiology and to facilitate development of new treatments for dysphagia caused by many diseases. The present study aimed to develop a new dysphagia model with reduced pharyngeal constriction during pharyngeal swallowing.

METHODS: We analyzed the dynamics of pharyngeal swallowing over time with the pharyngeal branches of the vagus nerve (Ph-X) bilaterally or unilaterally transected, using videofluoroscopic assessment of swallowing in guinea pigs. We also evaluated the detailed anatomy of the pharyngeal constrictor muscles after the denervation.

RESULTS: Videofluoroscopic examination of swallowing showed a significant increase in the pharyngeal area during swallowing after bilateral and unilateral sectioning of the Ph-X. The videofluoroscopy also showed significantly higher pharyngeal transit duration for bilateral and unilateral section groups. The thyropharyngeal muscle on the sectioned side was significantly thinner than that on the intact side. In contrast, the thickness of the cricopharyngeal muscles on the sectioned and intact sides were not significantly different. The mean thickness of the bilateral thyropharyngeal muscles showed a linear correlation to the pharyngeal area and pharyngeal transit duration.

DISCUSSION: Data obtained in this study suggest that denervation of the Ph-X could influence the strength of pharyngeal contraction during pharyngeal swallowing in relation to thickness of the pharyngeal constrictor muscles, resulting in a decrease in bolus speed. This experimental model may provide essential information (1) for the development of treatments for pharyngeal dysphagia and (2) on the mechanisms related to the recovery process, reinnervation, and nerve regeneration following injury and swallowing impairment possibly caused by medullary stroke, neuromuscular disease, or surgical damage from head and neck cancer.

PMID:38962483 | PMC:PMC11220121 | DOI:10.3389/fneur.2024.1401982

Br J Surg. 2024 Jul 2;111(7):znae143. doi: 10.1093/bjs/znae143.

ABSTRACT

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN.

METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes.

RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths.

CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).

PMID:38960881 | PMC:PMC11221944 | DOI:10.1093/bjs/znae143

Int Immunopharmacol. 2024 Jun 28;138:112555. doi: 10.1016/j.intimp.2024.112555. Online ahead of print.

ABSTRACT

The most common and serious complication among hospitalized and critically ill patients is sepsis-associated acute kidney damage (S-AKI), which raises the risk of comorbidities and is linked to a high mortality rate. Cholinergic anti-inflammatory pathway (CAP), an anti-inflammatory pathway mediated by the vagus nerve, acetylcholine, and α7 nicotinic acetylcholine receptors (α7nAChRs), offers new perspectives for the treatment of S-AKI. In this study, we investigated the role of CAP and α7nAChR in kidney injury by employing an LPS-induced septic kidney injury mouse model and GTS-21 intervention. C57BL/6 mice were injected with LPS, with or without GTS-21, in different subgroups. Kidney function was assessed by plasma creatinine, histology, and markers of kidney injury 24 h after intervention. The results demonstrated that GTS-21 could inhibit the systemic inflammatory response and directly protect the tubular cell injury from LPS. To explore the novel gene involved in this response, RNA sequencing of the renal proximal tubular epithelial cell (HK-2), pretreated with LPS and GTS-21, was conducted. The results indicate that GTS-21 administration reduces LPS-induced cytokines and chemokines secretion by HK-2, including CCL20, a potent chemokine attracting monocytes/macrophages. Furthermore, a macrophage transmigration assay revealed that GTS-21 inhibits macrophage transmigration by downregulating the expression of CCL20 in HK-2 cells. In conclusion, GTS-21, as an α7nAChR agonist, emerges as a noteworthy and versatile treatment for S-AKI. Its dual function of directly protecting renal tubular cells and regulating inflammatory responses represents a major advancement in the treatment of sepsis-induced AKI. This finding might pave the way for novel approaches to improving patient outcomes and reducing death rates in sepsis-related complications.

PMID:38943973 | DOI:10.1016/j.intimp.2024.112555

Epilepsia. 2024 Jun 29. doi: 10.1111/epi.18030. Online ahead of print.

ABSTRACT

OBJECTIVES: A surgical “treatment gap” in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts.

METHODS: In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results.

RESULTS: These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed.

SIGNIFICANCE: An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical “treatment gap.”

PMID:38943543 | DOI:10.1111/epi.18030

J Neural Eng. 2024 Jun 28. doi: 10.1088/1741-2552/ad5d16. Online ahead of print.

ABSTRACT

OBJECTIVE: Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive method of stimulating the vagus nerve, simultaneously affects the autonomic nervous system (ANS) and central nervous system (CNS) through efferent and afferent pathways. The purpose of this study is to analyze the effect of taVNS on the ANS and CNS through heart rate variability (HRV) and electroencephalography (EEG) parameters of identified responders.

APPROACH: Two sets of data were collected from each of 10 healthy adult male subjects in their 20s, and five HRV parameters from the time domain (RMSSD, pNN50, pNN30, pNN20, ppNNx) and two EEG parameters (power of alpha band, power of delta band) were extracted.

MAIN RESULTS: Based on pNN50, responders to taVNS were identified; among them, pNN50 (p = 0.0041) and ppNNx (p = 0.0037) showed significant differences before and after taVNS. At the same time, for alpha power and delta power of EEG, significant difference (p < 0.05) was observed in most channels after taVNS compared to before stimulation.

SIGNIFICANCE: This study demonstrated the validity of identifying responders using pNN50 and the influence of taVNS on both the ANS and CNS. We conclude that taVNS can be used to treat a variety of diseases and as a tool to help control the ANS and CNS.

PMID:38941990 | DOI:10.1088/1741-2552/ad5d16

Neuroscience. 2024 Jun 25:S0306-4522(24)00282-3. doi: 10.1016/j.neuroscience.2024.06.025. Online ahead of print.

ABSTRACT

The gastrointestinal tract exhibits coordinated muscle motility in response to food digestion, which is regulated by the central nervous system through autonomic control. The insular cortex is one of the brain regions that may regulate the muscle motility. In this study, we examined whether, and how, the insular cortex, especially the posterior part, regulates gastrointestinal motility by recording jejunal myoelectrical signals in response to feeding in freely moving male rats. Feeding was found to induce increases in jejunal myoelectrical signal amplitudes. This increase in the jejunal myoelectrical signals was abolished by vagotomy and pharmacological inhibition of the posterior insular cortex. Additionally, feeding induced a decrease and increase in sympathetic and parasympathetic nervous activities, respectively, both of which were eliminated by posterior insular cortical inhibition. These results suggest that the posterior insular cortex regulates jejunal motility in response to feeding by modulating autonomic tone.

PMID:38936460 | DOI:10.1016/j.neuroscience.2024.06.025

Langenbecks Arch Surg. 2024 Jun 27;409(1):198. doi: 10.1007/s00423-024-03392-y.

ABSTRACT

PURPOSE: The anatomical variations of the recurrent laryngeal nerve (RLN) are common during thyroidectomy. We aimed to evaluate the risk of RLN paralysis in case of its anatomical variations, retrospectively.

METHODS: The patients with primary thyroidectomy between January 2016 and December 2019 were enrolled. The effect of age, gender, surgical intervention, neuromonitorisation type, central neck dissection, postoperative diagnosis, neck side, extralaryngeal branching, non-RLN, relation of RLN to inferior thyroid artery (ITA), grade of Zuckerkandl tubercle on vocal cord paralysis (VCP) were investigated.

RESULTS: This study enrolled 1070 neck sides. The extralaryngeal branching rate was 35.5%. 45.9% of RLNs were anterior and 44.5% were posterior to the ITA, and 9.6% were crossing between the branches of the ITA. The rate of total VCP was 4.8% (transient:4.5%, permanent: 0.3%). The rates of total and transient VCP were significantly higher in extralaryngeal branching nerves compared to nonbranching nerves (6.8% vs. 3.6%, p = 0.018; 6.8% vs. 3.2%, p = 0.006, respectively). Total VCP rates were 7.2%, 2.5%, and 2.9% in case of the RLN crossing anterior, posterior and between the branches of ITA, respectively (p = 0.003). The difference was also significant regarding the transient VCP rates (p = 0.004). Anterior crossing pattern increased the total and transient VCP rates 2.8 and 2.9 times, respectively.

CONCLUSION: RLN crossing ITA anteriorly and RLN branching are frequent anatomical variations increasing the risk of VCP in thyroidectomy that cannot be predicted preoperatively. This study is the first one reporting that the relationship between RLN and ITA increased the risk of VCP.

PMID:38935142 | DOI:10.1007/s00423-024-03392-y