Can transcutaneous auricular vagus nerve stimulation mitigate vigilance loss? Examining the effects of stimulation at individualized versus constant current intensity.

According to the arousal model of vigilance, the locus coeruleus-norepinephrine (LC-NE) system modulates sustained attention over long periods by regulating physiological arousal. Recent research has proposed that transcutaneous auricular vagus nerve stimulation (taVNS) modulates indirect physiological markers of LC-NE activity, although its effects on vigilance have not yet been examined. Aiming to develop a safe and noninvasive procedure to prevent vigilance failures in prolonged tasks, the present study examined whether taVNS can mitigate vigilance loss while modulating indirect markers of LC-NE activity. Following a preregistered protocol (https://osf.io/tu2xy/), 50 participants completed three repeated sessions in a randomized order, in which either active taVNS at individualized intensity set by participant, active taVNS set at 0.5 mA for all participants, or sham taVNS, was delivered while performing an attentional and vigilance task (i.e., ANTI-Vea). Changes in salivary alpha-amylase and cortisol concentrations were measured as markers of LC-NE activity. Self-reports of feelings associated with stimulation and guessing rate of active/sham conditions supported the efficacy of the single-blind procedure. Contrary to our predictions, the observed vigilance decrement was not modulated by active taVNS. Pairwise comparisons showed a mitigation by active taVNS on cortisol reduction across time. Interestingly, Spearman's correlational analyses showed some interindividual effects of taVNS on indirect markers of LC-NE, evidenced by positive associations between changes in salivary alpha-amylase and cortisol in active but not sham taVNS. We highlight the relevance of replicating and extending the present outcomes, investigating further parameters of stimulation and its effects on other indirect markers of LC-NE activity.

Transcutaneous auricular vagus nerve stimulation modulates masseter muscle activity, pain perception, and anxiety levels in university students: a double-blind, randomized, controlled clinical trial.

Introduction: Chronic anxiety is a statemarked by sustained activation of the masseter muscle, manifesting in both mental and physical strain. This prolonged tension can significantly impact mental wellbeing and cognitive abilities, posing a risk for a range of health complications. This double-blind, randomized, controlled clinical trial investigated the impact of transcutaneous auricular vagus nerve stimulation (TAVNS) on masseter muscle activity, pressure pain threshold (PPT), and anxiety levels in university students with elevated anxiety. Methods: Forty-two participants meeting inclusion criteria were randomly assigned to either active TAVNS or sham TAVNS groups. Various parameters, including masseter muscle electromyographic (EMG) signals, PPT, and Beck Anxiety Inventory (BAI) scores, were assessed before pretreatment, immediately after the intervention week, and 2 weeks follow-up. Results: Active TAVNS significantly reduced both left and right masseter activation during resting mandibular position, persisting for 2 weeks post-intervention. Additionally, TAVNS induced a lasting decrease in both left and right masseter PPT, indicative of altered pain perception. Notably, BAI scores showed a substantial reduction, emphasizing TAVNS as a potential intervention for anxiety, with effects maintained at the 2-week follow-up. Discussion: This study provides comprehensive insights into the multifaceted effects of TAVNS on physiological and psychological aspects associated with anxiety in university students. The promising results underscore TAVNS as a potential neuromodulatory intervention for anxiety-related conditions, warranting further research and clinical exploration. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-4s4kt2r.

Age as an Effect Modifier of the Effects of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) on Heart Rate Variability in Healthy Subjects.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

Effects of Transcutaneous Auricular Vagus Nerve Stimulation on the P300: Do Stimulation Duration and Stimulation Type Matter?

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has attracted increasing interest as a neurostimulation tool with potential applications in modulating cognitive processes such as attention and memory, possibly through the modulation of the locus-coeruleus noradrenaline system. Studies examining the P300 brain-related component as a correlate of noradrenergic activity, however, have yielded inconsistent findings, possibly due to differences in stimulation parameters, thus necessitating further investigation. In this event-related potential study involving 61 participants, therefore, we examined how changes in taVNS parameters, specifically stimulation type (interval vs. continuous stimulation) and duration, influence P300 amplitudes during a visual novelty oddball task. Although no effects of stimulation were found over the whole cluster and time window of the P300, cluster-based permutation tests revealed a distinct impact of taVNS on the P300 response for a small electrode cluster, characterized by larger amplitudes observed for easy targets (i.e., stimuli that are easily discernible from standards) following taVNS compared to sham stimulation. Notably, our findings suggested that the type of stimulation significantly modulated taVNS effects on the P300, with continuous stimulation showing larger P300 differences (taVNS vs. sham) for hard targets and standards compared to interval stimulation. We observed no interaction effects of stimulation duration on the target-related P300. While our findings align with previous research, further investigation is warranted to fully elucidate the influence of taVNS on the P300 component and its potential utility as a reliable marker for neuromodulation in this field.

Transcutaneous auricular vagus nerve stimulation improves social deficits through the inhibition of IL-17a signaling in a mouse model of autism.

Background: Maternal exposure to inflammation is one of the causes of autism spectrum disorder (ASD). Electrical stimulation of the vagus nerve exerts a neuroprotective effect via its anti-inflammatory action. We thus investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) can enhance social abilities in a mouse model of ASD induced by maternal immune activation (MIA). Methods: ASD mouse model were constructed by intraperitoneal injection of polyinosinic:polycytidylic acid (poly (I:C)). TaVNS with different parameters were tested in ASD mouse model and in C57BL/6 mice, then various behavioral tests and biochemical analyses related to autism were conducted. ASD model mice were injected with an interleukin (IL)-17a antibody into the brain, followed by behavioral testing and biochemical analyses. Results: TaVNS reduced anxiety, improved social function, decreased the number of microglia, and inhibited M1 polarization of microglia. Additionally, taVNS attenuated the expression of the IL-17a protein in the prefrontal cortex and blood of ASD model mice. To examine the possible involvement of IL-17a in taVNS-induced neuroprotection, we injected an IL-17a antibody into the prefrontal cortex of ASD model mice and found that neutralizing IL-17a decreased the number of microglia and inhibited M1 polarization. Furthermore, neutralizing IL-17a improved social function in autism model mice. Conclusion: Our study revealed that reduced neuroinflammation is an important mechanism of taVNS-mediated social improvement and neuroprotection against autism. This effect of taVNS could be attributed to the inhibition of the IL-17a pathway.

Evidence of bottom-up homeostatic modulation induced taVNS during emotional and Go/No-Go tasks.

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.

Transcutaneous auricular vagus nerve stimulation may benefit from the addition of N-acetylcysteine to facilitate motor learning in infants of diabetic mothers failing oral feeds.

Objective: This study aims to determine if pretreating with enteral N-acetylcysteine (NAC) improves CNS oxidative stress and facilitates improvement in oromotor skills during transcutaneous auricular nerve stimulation (taVNS) paired with oral feedings in infants of diabetic mothers (IDMs) who are failing oral feeds. Methods: We treated 10 IDMs who were gastrostomy tube candidates in an open-label trial of NAC and taVNS paired with oral feeding. NAC (75 or 100 mg/kg/dose) was given by nasogastric (NG) administration every 6 h for 4 days, then combined with taVNS paired with 2 daily feeds for another 14 days. NAC pharmacokinetic (PK) parameters were determined from plasma concentrations at baseline and at steady state on day 4 of treatment in conjunction with magnetic resonance spectroscopic (MRS) quantification of CNS glutathione (GSH) as a marker of oxidative stress. We compared increases in oral feeding volumes before and during taVNS treatment and with a prior cohort of 12 IDMs who largely failed to achieve full oral feeds with taVNS alone. Results: NAC 100 mg/kg/dose every 6 h NG resulted in plasma [NAC] that increased [GSH] in the basal ganglia with a mean of 0.13 ± 0.08 mM (p = 0.01, compared to baseline). Mean daily feeding volumes increased over 14 days of NAC + taVNS compared to the 14 days before treatment and compared to the prior cohort of 12 IDMs treated with taVNS alone. Seven IDMs reached full oral feeds sufficient for discharge, while three continued to have inadequate intake. Conclusion: In IDM failing oral feeds, NAC 100 mg/kg/dose every 6 h NG for 4 days before and during taVNS paired with oral feeding increased CNS GSH, potentially mitigating oxidative stress, and was associated with improving functional feeding outcomes compared to taVNS alone in a prior cohort. This represents a novel approach to neuromodulation and supports the concept that mitigation of ongoing oxidative stress may increase response to taVNS paired with a motor task.

The Effect of taVNS at 25 Hz and 100 Hz on Parkinson's Disease Gait-A Randomized Motion Sensor Study.

BACKGROUND: Transcutaneous electrostimulation of the auricular branch of the vagal nerve (taVNS) has the propensity to reach diffuse neuromodulatory networks, which are dysfunctional in Parkinson's disease (PD). Previous studies support the use of taVNS as an add-on treatment for gait in PD. OBJECTIVES: We assessed the effect of taVNS at 25 Hz (taVNS25), taVNS at 100 Hz (taVNS100), and sham earlobe stimulation (sVNS) on levodopa responsive (arm swing velocity, arm range of motion, stride length, gait speed) and non-responsive gait characteristics (arm range of motion asymmetry, anticipatory postural adjustment [APA] duration, APA first step duration, APA first step range of motion), and turns (first turn duration, double 360° turn duration, steps per turn) in advanced PD. METHODS: In our double blind sham controlled within-subject randomized trial, we included 30 PD patients (modified Hoehn and Yahr stage, 2.5-4) to assess the effect of taVNS25, taVNS100, and sVNS on gait characteristics measured with inertial motion sensors during the instrumented stand and walk test and a double 360° turn. Separate generalized mixed models were built for each gait characteristic. RESULTS: During taVNS100 compared to sVNS arm swing velocity (P = 0.030) and stride length increased (P = 0.027), and APA duration decreased (P = 0.050). During taVNS25 compared to sVNS stride length (P = 0.024) and gait speed (P = 0.021) increased and double 360° turn duration decreased (P = 0.039). CONCLUSIONS: We have found that taVNS has a frequency specific propensity to improve stride length, arm swing velocity, and gait speed and double 360° turn duration in PD patients. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Possible mechanisms of auricular acupoint stimulation in the treatment of migraine by activating auricular vagus nerve. / 从耳迷走神经探讨耳穴治疗偏头痛的可能机制.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Monobenzone-Induced Vitiligo in Mice.

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown. This study aimed to explore the therapeutic effects of taVNS in a mouse model of vitiligo induced by monobenzone. Initially, a quantitative assessment of the treatment effects on vitiligo mice was conducted using a scoring system, revealing that taVNS significantly alleviated symptoms, particularly by reducing the depigmented areas. Subsequent immunohistochemical analysis revealed the impact of taVNS treatment on melanocyte granules, mitigating pigment loss in the skin of monobenzone-induced vitiligo mice. Further analysis indicated that taVNS exerted its therapeutic effects through multiple mechanisms, including the regulation of oxidative stress, enhancement of antioxidant capacity, promotion of tyrosine synthesis, and suppression of inflammatory responses. The conclusions of this study not only emphasize the potential value of taVNS in vitiligo therapy, but also lay a foundation for future research into the mechanisms and clinical applications of taVNS.

Tonic and phasic transcutaneous auricular vagus nerve stimulation (taVNS) both evoke rapid and transient pupil dilation.

BACKGROUND: Transcutaneous auricular vagus nerve stimulation (tVNS or taVNS) is a non-invasive method of electrical stimulation of the afferent pathway of the vagus nerve, suggested to drive changes in putative physiological markers of noradrenergic activity, including pupil dilation. OBJECTIVE: However, it is unknown whether different taVNS modes can map onto the phasic and tonic modes of noradrenergic activity. The effects of taVNS on pupil dilation in humans are inconsistent, largely due to differences in stimulation protocols. Here, we attempted to address these issues. METHODS: We investigated pupil dilation under phasic (1 s) and tonic (30 s) taVNS, in a pre-registered, single-blind, sham-controlled, within-subject cross-over design, in the absence of a behavioural task. RESULTS: Phasic taVNS induced a rapid increase in pupil size over baseline, significantly greater than under sham stimulation, which rapidly declined after stimulation offset. Tonic taVNS induced a similarly rapid (and larger than sham) increase in pupil size over baseline, returning to baseline within 5 s, despite the ongoing stimulation. Thus, both active and sham tonic modes closely resembled the phasic effect. There were no differences in tonic baseline pupil size, and no sustained effects of stimulation on tonic baseline pupil size. CONCLUSIONS: These results suggest that both phasic- and tonic-like taVNS under the standard stimulation parameters may modulate primarily the phasic mode of noradrenergic activity, as indexed by evoked pupil dilation, over and above somatosensory effects. This result sheds light on the temporal profile of phasic and tonic stimulation, with implications for their applicability in further research.

Transcutaneous auricular vagus nerve stimulation modulates the processing of interoceptive prediction error signals and their role in allostatic regulation.

It has recently been suggested that predictive processing principles may apply to interoception, defined as the processing of hormonal, autonomic, visceral, and immunological signals. In the current study, we aimed at providing empirical evidence for the role of cardiac interoceptive prediction errors signals on allostatic adjustments, using transcutaneous auricular vagus nerve stimulation (taVNS) as a tool to modulate the processing of interoceptive afferents. In a within-subject design, participants performed a cardiac-related interoceptive task (heartbeat counting task) under taVNS and sham stimulation, spaced 1-week apart. We observed that taVNS, in contrast to sham stimulation, facilitated the maintenance of interoceptive accuracy levels over time (from the initial, stimulation-free, baseline block to subsequent stimulation blocks), suggesting that vagus nerve stimulation may have helped to maintain engagement to cardiac afferent signals. During the interoceptive task, taVNS compared to sham, produced higher heart-evoked potentials (HEP) amplitudes, a potential readout measure of cardiac-related prediction error processing. Further analyses revealed that the positive relation between interoceptive accuracy and allostatic adjustments-as measured by heart rate variability (HRV)-was mediated by HEP amplitudes. Providing initial support for predictive processing accounts of interoception, our results suggest that the stimulation of the vagus nerve may increase the precision with which interoceptive signals are processed, favoring their influence on allostatic adjustments.

Pairing taVNS and CIMT is feasible and may improve upper extremity function in infants.

In this study we combined non-invasive transcutaneous auricular vagal nerve stimulation (taVNS) with 40 h of constraint induced movement therapy (CIMT) in infants. All infants completed the full intervention with no adverse events. Therapists were able to maintain high treatment fidelity and reported high ratings for ease of use and child tolerance. Preliminary results show promising gains on motor outcomes: Mean QUEST increase 19.17 (minimal clinically important difference, MCID 4.89); Mean GMFM increase 13.33 (MCID 1%-3%). Infants also exceeded expectations on Goal Attainment Scores (+1). Early data is promising that taVNS paired with intensive motor CIMT is feasible, reliable, and safe in young infants with hemiplegia, and may help harness activity-dependent plasticity to enhance functional movement.

Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review.

BACKGROUND: The discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD. METHODS: Two searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies. RESULTS: Only 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression. CONCLUSIONS: Data on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.

Non-invasive vagus nerve stimulation and the motivation to work for rewards: A replication of Neuser et al. (2020, Nature Communications).

The vagus nerve is thought to be involved in the allostatic regulation of motivation and energy metabolism via gut-brain interactions. A recent study by Neuser and colleagues (2020) provided novel evidence for this process in humans, by reporting a positive effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the invigoration of reward-seeking behaviors, especially for food rewards. We conducted an independent direct replication of Neuser et al. (2020), to assess the robustness of their findings. Following the original study, we used a single-blind, sham-controlled, randomized cross-over design. We applied left-sided taVNS in healthy human volunteers (n = 40), while they performed an effort allocation task in which they had to work for monetary and food rewards. The replication study was purely confirmatory in that it strictly followed the analysis plans and scripts used by Neuser et al. Although, in line with Neuser et al., we found strong effects of task variables on effort invigoration and effort maintenance, we failed to replicate their key finding: taVNS did not increase the strength of invigoration (p = .62); the data were five times more likely (BF10 = 0.19) under the null hypothesis. We also found substantial evidence against an effect of taVNS on effort maintenance (p = .50; BF10 = 0.20). Our results provide evidence against the idea that left-sided taVNS boosts the motivational drive to work for rewards. Our study also highlights the need for direct replications of influential taVNS studies.

Efficacy of transauricular vagus nerve stimulation for the treatment of chemotherapy-induced painful peripheral neuropathy: a randomized controlled exploratory study.

BACKGROUND: Chemotherapy-induced painful peripheral neuropathy (CIPN) is a common adverse event in cancer patients, and there is still a lack of effective treatment. Transauricular vagal nerve stimulation (taVNS) is a minimally invasive treatment, but there are few reports regarding its efficacy for CIPN. OBJECTIVE: To investigate the efficacy and possible mechanism of taVNS in patients with CIPN. METHODS: Twenty-seven patients with CIPN were randomly divided into a taVNS group (n = 14) and a sham stimulation (SS) group (n = 13). A numerical rating scale (NRS) for pain, NCICTCAE 4.0 (neurotoxicity classification), quantitative sensory test (QST), Short-Form-Health Survey-12 (SF-12), and Athens Insomnia Scale (AIS) were administered before the intervention (D-10) and on the day after the intervention (D0), and the inflammatory cytokines in plasma were also measured. The NRS, NCI-CTCAE 4.0, SF-12, and AIS were administered again at D30 and D90. RESULTS: Compared with the SS group, the NRS and AIS in the taVNS group were significantly lower at D0. The impact lasted until D30. There were no statistically significant differences in the NRS and AIS between the 2 groups at D90. On D30, the mental component score of the SF-12 was significantly higher in the taVNS group than in the SS group. No adverse events were found. There was no significant difference in QST and plasma inflammatory cytokines between the 2 groups. CONCLUSION: taVNS can relieve chemotherapy-induced neuropathic pain in the short term, can improve sleep status and quality of life, and is expected to become a novel clinical treatment method for CIPN.

Transcutaneous auricular vagus nerve stimulation therapy in patients with cognitively preserved structural focal epilepsy: A case series report.

OBJECTIVE: Transcutaneous auricular vagus nerve stimulation (taVNS) was performed in two patients suffering structural focal epilepsy with preserved intellectual ability to show the feasibility of taVNS for specific patient groups. CASE PRESENTATIONS: Patient 1 was a 24-year-old woman with frontal lobe epilepsy who had weekly hyperkinetic seizures despite multiple anti-seizure medications. Patient 2 was a 27-year-old woman with parietal lobe epilepsy and focal cortical dysplasia in the vicinity of the lipoma in the corpus callosum. She experienced weekly focal-impaired awareness seizures even with anti-seizure medication. taVNS was applied to the left earlobe of both patients at 1.5 mA, 25 Hz, 250 µs pulse width, and 30 s stimulation with 30 s rest for 4 h per day. Over an 8-week baseline and 20 weeks of stimulation, the rate of reduction in seizure frequency was evaluated, along with quality-of-life using the Short-Form 36-Item Health survey. RESULTS: At baseline, we measured up to 11 and 12 focal seizures per week in Patient 1 and 2, respectively, with both patients achieving seizure freedom after 4 and 20 weeks taVNS, respectively. Patient 1 and 2 were observed for 18 and 14 months, respectively, including the clinical trial and follow-up observation period. Quality-of-life ratings increased in both patients, and no significant adverse events occurred during the study period. During the maintenance period after 20 weeks, seizures remained absent in Patient 1, and seizures remained reduced in Patient 2. CONCLUSION: Our results demonstrate that taVNS may be a promising tool for structural focal epilepsy with preserved cognitive function. A multicenter double-blind clinical trial is needed to confirm the role of taVNS as an anti-seizure tool.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.