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Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cortical Excitability in Healthy Adults

Neuromodulation. 2024 Jun 14:S1094-7159(24)00107-7. doi: 10.1016/j.neurom.2024.05.004. Online ahead of print.

ABSTRACT

OBJECTIVE: Vagus nerve stimulation (VNS) has recently been reported to exert additional benefits for functional recovery in patients with brain injury. However, the mechanisms underlying these effects have not yet been elucidated. This study examined the effects of transcutaneous auricular VNS (taVNS) on cortical excitability in healthy adults.

MATERIALS AND METHODS: We recorded subthreshold and suprathreshold single- and paired-pulse motor-evoked potentials (MEPs) in the right-hand muscles of 16 healthy adults by stimulating the left primary motor cortex. Interstimulus intervals were set at 2 milliseconds and 3 milliseconds for intracortical inhibition (ICI), and 10 milliseconds and 15 milliseconds for intracortical facilitation (ICF). taVNS was applied to the cymba conchae of both ears for 30 minutes. The intensity of taVNS was set to a maximum tolerable level of 1.95 mA. MEPs were measured before stimulation, 20 minutes after the beginning of the stimulation, and 10 minutes after the cessation of stimulation.

RESULTS: The participants’ age was 33.25 ± 7.08 years, and nine of 16 were male. No statistically significant changes were observed in the mean values of the single-pulse MEPs before, during, or after stimulation. Although the ICF showed an increasing trend after stimulation, the changes in ICI and ICF were not significant, primarily because of the substantial interindividual variability.

CONCLUSIONS: The effect of taVNS on cortical excitability varied in healthy adults. An increase in ICF was observed after taVNS, although the difference was not statistically significant. Our findings contribute to the understanding of the mechanisms by which taVNS is effective in patients with brain disorders.

PMID:38878053 | DOI:10.1016/j.neurom.2024.05.004

Neurorehabilitation with vagus nerve stimulation: a systematic review

Front Neurol. 2024 May 30;15:1390217. doi: 10.3389/fneur.2024.1390217. eCollection 2024.

ABSTRACT

OBJECTIVE: To systematically review vagus nerve stimulation (VNS) studies to present data on the safety and efficacy on motor recovery following stroke, traumatic brain injury (TBI), and spinal cord injury (SCI).

METHODS: Data sources: PubMed, EMBASE, SCOPUS, and Cochrane.

STUDY SELECTION: Clinical trials of VNS in animal models and humans with TBI and SCI were included to evaluate the effects of pairing VNS with rehabilitation therapy on motor recovery.

DATA EXTRACTION: Two reviewers independently assessed articles according to the evaluation criteria and extracted relevant data electronically.

DATA SYNTHESIS: Twenty-nine studies were included; 11 were animal models of stroke, TBI, and SCI, and eight involved humans with stroke. While there was heterogeneity in methods of delivering VNS with respect to rehabilitation therapy in animal studies and human non-invasive studies, a similar methodology was used in all human-invasive VNS studies. In animal studies, pairing VNS with rehabilitation therapy consistently improved motor outcomes compared to controls. Except for one study, all human invasive and non-invasive studies with controls demonstrated a trend toward improvement in motor outcomes compared to sham controls post-intervention. However, compared to non-invasive, invasive VNS, studies reported severe adverse events such as vocal cord palsy, dysphagia, surgical site infection, and hoarseness of voice, which were found to be related to surgery.

CONCLUSION: Our review suggests that VNS (non-invasive or invasive) paired with rehabilitation can improve motor outcomes after stroke in humans. Hence, VNS human studies are needed in these populations (referring to SCI and TBI?) or just SCI. There are risks related to device implantation to deliver invasive VNS compared to non-invasive VNS. Future human comparison studies are required to study and quantify the efficacy vs. risks of paired VNS delivered via different methods with rehabilitation, which would allow patients to make an informed decision.

SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330653.

PMID:38872818 | PMC:PMC11169586 | DOI:10.3389/fneur.2024.1390217

Enteric neuropathy and the vagus nerve: Therapeutic implications

Neurogastroenterol Motil. 2024 Jun 14:e14842. doi: 10.1111/nmo.14842. Online ahead of print.

ABSTRACT

Enteric neuropathies are characterized by abnormalities of gut innervation, which includes the enteric nervous system, inducing severe gut dysmotility among other dysfunctions. Most of the gastrointestinal tract is innervated by the vagus nerve, the efferent branches of which have close interconnections with the enteric nervous system and whose afferents are distributed throughout the different layers of the digestive wall. The vagus nerve is a key element of the autonomic nervous system, involved in the stress response, at the interface of the microbiota-gut-brain axis, has anti-inflammatory and prokinetic properties, modulates intestinal permeability, and has a significant capacity of plasticity and regeneration. Targeting these properties of the vagus nerve, with vagus nerve stimulation (or non-stimulation/ pharmacological methods), could be of interest in the therapeutic management of enteric neuropathies.

PMID:38873822 | DOI:10.1111/nmo.14842

Transcutaneous Auricular Vagus Nerve Stimulation Ameliorates Preeclampsia-Induced Apoptosis of Placental Trophoblastic Cells Via Inhibiting the Mitochondrial Unfolded Protein Response

Neurosci Bull. 2024 Jun 14. doi: 10.1007/s12264-024-01244-9. Online ahead of print.

ABSTRACT

Preeclampsia is a serious obstetric complication. Currently, there is a lack of effective preventive approaches for this disease. Recent studies have identified transcutaneous auricular vagus nerve stimulation (taVNS) as a potential novel non-pharmaceutical therapeutic modality for preeclampsia. In this study, we investigated whether taVNS inhibits apoptosis of placental trophoblastic cells through ROS-induced UPRmt. Our results showed that taVNS promoted the release of acetylcholine (ACh). ACh decreased the expression of UPRmt by inhibiting the formation of mitochondrial ROS (mtROS), presumably through M3AChR. This reduced the release of pro-apoptotic proteins (cleaved caspase-3, NF-κB-p65, and cytochrome C) and helped preserve the morphological and functional integrity of mitochondria, thus reducing the apoptosis of placental trophoblasts, improving placental function, and relieving preeclampsia. Our study unravels the potential pathophysiological mechanism of preeclampsia. In-depth characterization of the UPRmt is essential for developing more effective therapeutic strategies for preeclampsia targeting mitochondrial function.

PMID:38874677 | DOI:10.1007/s12264-024-01244-9

Characterizing the safety profile of vagus nerve stimulation devices for epilepsy from 21,448 manufacturer and user reports

J Neurosurg. 2024 Jun 14:1-15. doi: 10.3171/2024.3.JNS231942. Online ahead of print.

ABSTRACT

OBJECTIVE: This study summarizes medical device reports (MDRs) associated with adverse events for vagus nerve stimulation (VNS) devices indicated for epilepsy as reported by the Manufacturer and User Facility Device Experience (MAUDE) database of the US Food and Drug Administration.

METHODS: The MAUDE database was surveyed for MDRs from November 2013 to September 2022 regarding VNS devices for epilepsy. Event descriptions, device problems, correlated patient consequences, and device models were grouped and analyzed in Python. Based on event description, revision surgeries and other unique events were identified. Revenue from VNS device sales was used to approximate growth in their use over time.

RESULTS: A total of 21,448 MDRs met the inclusion criteria. High VNS impedance, the most prevalent device malfunction overall (17.0% of MDRs), was the most common factor for 18 of the 102 encountered patient problems and led to 1001 revision surgeries (3371 total revisions). Included in those 18 device malfunctions were 3 of the top 6 occurring patient problems: seizure recurrence (9.9% associated with high impedance; encompassed focal, absence, and grand mal subtypes), death (1.3%), and generalized pain (7.9%). The next 4 top cited device malfunctions-lead fracture (13.7% of MDRs), operational issue (6.6%), battery problem holding charge (4.2%), and premature end-of-life indicator (2.9%)-differed widely in their percentage of cases that did not impact patients (77.4%, 57.3%, 48.9%, and 92.2%, respectively), highlighting differing malfunction severities. Seizure recurrence, the most prevalent patient impact, was the outcome most associated with 32 of the 68 encountered device problems, including high impedance (12.8%), lead fracture (12.2%), operational issue (18.4%), battery problem holding charge (31.2%), and premature end-of-life indicator (8.9%), which comprised the top 5 occurring device problems. In general, MDRs spanned a diverse range including device age, hardware, software, and surgeon or manufacturer error. Trends were seen over time with declining annual MDRs coupled with a rise in the use of VNS devices as gauged by revenue growth. Shifting device and patient problem profiles were also seen in successive models, reflecting engineering updates.

CONCLUSIONS: This study characterizes the most common and consequential side effects of VNS devices for epilepsy while clarifying likely causes. In addition, the outcomes of 68 distinct device malfunctions were identified, including many not ubiquitously present in literature, lending critical perspective to clinical practice.

PMID:38875724 | DOI:10.3171/2024.3.JNS231942

State- and frequency-dependence in autonomic rebalance mediated by intradermal auricular electroacupuncture stimulation

Front Neurosci. 2024 May 23;18:1367266. doi: 10.3389/fnins.2024.1367266. eCollection 2024.

ABSTRACT

BACKGROUND: Vagus nerve stimulation (VNS) improves diseases such as refractory epilepsy and treatment-resistant depression, likely by rebalancing the autonomic nervous system (ANS). Intradermal auricular electro-acupuncture stimulation (iaES) produces similar effects. The aim of this study was to determine the effects of different iaES frequencies on the parasympathetic and sympathetic divisions in different states of ANS imbalance.

METHODS: We measured heart rate variability (HRV) and heart rate (HR) of non-modeled (normal) rats with the treatment of various frequencies to determine the optimal iaES frequency. The optimized iaES frequency was then applied to ANS imbalance model rats to elucidate its effects.

RESULTS: 30 Hz and 100 Hz iaES clearly affected HRV and HR in normal rats. 30 Hz iaES increased HRV, and decreased HR. 100 Hz iaES decreased HRV, and increased HR. In sympathetic excited state rats, 30 Hz iaES increased HRV. 100 Hz iaES increased HRV, and decreased HR. In parasympathetic excited state rats, 30 Hz and 100 Hz iaES decreased HRV. In sympathetic inhibited state rats, 30 Hz iaES decreased HRV, while 100 Hz iaES decreased HR. In parasympathetic inhibited rats, 30 Hz iaES decreased HR and 100 Hz iaES increased HRV.

CONCLUSION: 30 Hz and 100 Hz iaES contribute to ANS rebalance by increasing vagal and sympathetic activity with different amplifications. The 30 Hz iaES exhibited positive effects in all the imbalanced states. 100 Hz iaES suppressed the sympathetic arm in sympathetic excitation and sympathetic/parasympathetic inhibition and suppressed the vagal arm and promoted the sympathetic arm in parasympathetic excitation and normal states.

PMID:38846714 | PMC:PMC11153749 | DOI:10.3389/fnins.2024.1367266