A review of vagus nerve stimulation as a therapeutic intervention

Calvino B.

Gidron Y., Levy E., Ryder C.H., Shaul S., Sirota R., Atias D.

Background: The ongoing conflict in Ukraine has forced numerous migrants into neighboring countries, many suffering from pre-existing or newly acquired physical and mental health conditions. Addressing these complex challenges in humanitarian settings requires innovative, evidence-based interventions that are cost-effective and easy to administer. Drawing upon research highlighting the vagus nerve’s role in regulating well-being, we hypothesized that vagal nerve activation could offer a promising therapeutic approach. Method: We conducted a proof-of-concept study in which 21 Ukrainian forced migrants were trained in a biofeedback-guided paced breathing intervention designed to stimulate the vagus nerve and promote self-regulation of stress response systems. Changes in pain perception, perceived stress, blood pressure, and heart rate were assessed before and after the vagal breathing intervention using a t-test. Correlations were examined at baseline. Results: Statistically significant improvements were observed in all measures except systolic blood pressure, providing preliminary evidence for the efficacy of vagal nerve activation in alleviating stress-related health symptoms. Conclusions: This study demonstrates the feasibility and therapeutic potential of a vagal nerve-activating intervention in a humanitarian setting. These findings warrant replication in larger, controlled trials. If substantiated, this low-cost, scalable intervention could help mitigate health burdens among forced migrant populations worldwide.

Chávez Cerda J., Acedo Reina E., Dereli A.S., Vande Perre L., Raffoul R., Verstraeten M., Ngan Yamb M., Germany Morrison E., Collard E., Apaire A., Doguet P., Garnier J., Delbeke J., El Tahry R., Nonclercq A.

Despite the proven efficacy of vagus nerve stimulation (VNS) in seizure control, its precise mechanism of action remains unclear. VNS is known to impact the cardiorespiratory system. In this study, we explored the effects of standard and breathing-synchronized VNS on heart and respiratory rates in anesthetized epileptic rats, as well as their impact on seizure susceptibility. Seizures were induced in rats by intravenous pentylenetetrazol (PTZ) infusion. Three animal groups (n = 4) were subjected to different types of stimulation: Sham VNS, Standard VNS, and Breathing-Synchronized VNS. Measurements included respiration, electrocardiogram, electroencephalogram, and vagal electroneurogram. Each experiment began with a 5-min baseline period, followed by PTZ infusion until tonic–clonic seizure onset, confirmed by video recording and electroencephalogram. Results indicate that the stimulation significantly decreased the heart rate below baseline levels for standard VNS (−120.0 ± 69.1 bpm) and breathing-synchronized VNS (−84.9 ± 61.0 bpm), overcoming the heart rate increasing effect of PTZ infusion observed in the sham VNS (+79.2 ± 35.5 bpm), and there was no recovery during OFF periods. Regarding the breathing rate changes, the sham VNS group presented a slight increase with respect to baseline (+13.6 ± 1.8 bpm). The stimulation slightly increased the average breathing rate for standard VNS (+13.0 ± 14.6 bpm) and breathing-synchronized VNS (+13.7 ± 10.4 bpm), however with significantly enlarged standard deviation. More specifically, the breathing rate presented a pattern that suggests that the rats experienced respiratory hypoxia under stimulation. The VNS modulation of the heart rate and breathing rate in the standard VNS group was similar in the breathing-synchronized VNS, suggesting that the VNS effect is cumulative. Unexpectedly, the sham VNS group required a higher PTZ dose (79.7 ± 13.4 mg/kg) to reach tonic–clonic seizures compared to the standard VNS group (57.9 ± 9.8 mg/kg), and the breathing-synchronized VNS group (60.0 ± 8.7 mg/kg), pointing to an increased seizure susceptibility of VNS in this particular model. Additionally, the latency of the seizures was longer in the sham VNS (291.5 ± 84.4 s) compared to standard VNS (200.5 ± 59.5 s) and breathing-synchronized VNS (206.9 ± 66.0 s), meaning that the seizures under stimulation were starting earlier. A significant linear relationship was found between heart rate and respiratory rate changes, and seizure susceptibility (R2 = 0.62, p-value = 0.012). We hypothesize that the significant drop in heart rate and the presence of altered respiration patterns, such as apneas or changes in breathing rates, caused by VNS, are related to hypoxia and hypotension conditions, which could increase susceptibility to PTZ. Future investigations with larger sample sizes, incorporating blood pressure and oxygen saturation monitoring, are needed to sort out the role of hypoxia and hypotension as potential covariates affecting the seizure susceptibility caused by overstimulation. Such a finding would support the idea that VNS safety and efficacy require precise adjustments.

Patros M., Sivathamboo S., Simpson H.D., O'Brien T.J., Macefield V.G.

AbstractThe vagus nerve is the longest cranial nerve, with much of its territory residing outside the head, in the neck, chest and abdomen. Although belonging to the parasympathetic division of the autonomic nervous system, it is dominated by sensory axons originating in the heart, lungs and airways and the gastrointestinal tract. Electrical stimulation of the cervical vagus nerve via surgically implanted cuff electrodes has been used clinically for the treatment of drug‐resistant epilepsy for three decades but has also shown efficacy in the treatment of drug‐resistant depression and certain gastrointestinal disorders. Through consideration of the anatomical composition of the vagus nerve, its physiology and its distribution throughout the body, we review the effects of vagus nerve stimulation in the context of drug‐resistant epilepsy. This narrative review is divided into two sections: part one surveys the anatomy and physiology of the vagus nerve, and part two describes what we know about how vagus nerve stimulation works. image

Pervaz I., Thurn L., Vezzani C., Kaluza L., Kühnel A., Kroemer N.B.

Abouelmagd M.E., Yousef O., Ibrahim I.A., Elshahat A.

Baldwin A., States G., Pikov V., Gunalan P., Elyahoodayan S., Kilgore K., Meng E.

Aoyagi K., Rivas E., Shababi R., Edwards R., LaValley M., Lechuga J., Napadow V., Neogi T.

Vitello M.M., Laureys S., Thibaut A., Gosseries O.

Jerman I., Škafar M., Pihir J., Senica M.

Clerici L., Bottari D., Bottari B.

Abstract Purpose of Review This review explores the intricate relationships among the gut microbiota, dietary patterns, and mental health, focusing specifically on depression. It synthesizes insights from microbiological, nutritional, and neuroscientific perspectives to understand how the gut-brain axis influences mood and cognitive function. Recent Findings Recent studies underscore the central role of gut microbiota in modulating neurological and psychological health via the gut-brain axis. Key findings highlight the importance of dietary components, including probiotics, prebiotics, and psychobiotics, in restoring microbial balance and enhancing mood regulation. Different dietary patterns exhibit a profound impact on gut microbiota composition, suggesting their potential as complementary strategies for mental health support. Furthermore, mechanisms like tryptophan metabolism, the HPA axis, and microbial metabolites such as SCFAs are implicated in linking diet and microbiota to depression. Clinical trials show promising effects of probiotics in alleviating depressive symptoms. Summary This review illuminates the potential of diet-based interventions targeting the gut microbiota to mitigate depression and improve mental health. While the interplay between microbial diversity, diet, and brain function offers promising therapeutic avenues, further clinical research is needed to validate these findings and establish robust, individualized treatment strategies.

Faraji N., Payami B., Ebadpour N., Gorji A.

Lauinger A.R., Sepe J.J.

With an aging population, the incidence of both ischemic heart disease and strokes have become the most prevalent diseases globally. These diseases have similar risk factors, such as hypertension, diabetes, and smoking. However, there is also evidence of a relationship between the heart and the brain, referred to as the heart–brain axis. In this relationship, dysfunction of either organs can lead to injury to the other. There are several proposed physiologies to explain this relationship. These theories usually involve vascular, neuromodulatory, and inflammatory processes; however, few articles have explored and compared these different mechanisms of interaction between the heart and brain. A better understanding of the heart–brain axis can inform physicians of current and future treatment and preventive care options in heart and brain pathologies. The relationship between the brain and heart depends on inflammation, vascular anatomy and function, and neuromodulation. The pathways connecting these organs often become injured or dysfunctional when a major pathology, such as a myocardial infarction or stroke, occurs. This leads to long-term impacts on the patient’s overall health and risk for future disease. This study summarizes the current research involved in the heart–brain axis, relates these interactions to different diseases, and proposes future research in the field of neurocardiology. Conditions of the brain and heart are some of the most prevalent diseases. Through understanding the connection between these two organs, we can help inform patients and physicians of novel therapeutics for these pathologies.

Kimmell S., Farley J., Bautista A., Abd-Elsayed A.

Russo M.A., Chakravarthy K., Kinfe T.M.