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.

The effects of frequency-specific, non-invasive, median nerve stimulation on food-related attention and appetite.

Median nerve stimulation (MNS) in the existing literature has been used for treating gastrointestinal disorders and amelioration of nausea and vomiting. Recently, studies have shown that MNS can also exert effects on olfactory performances and corresponding anatomical regions through the activation of vagal pathways. This study aimed to test effects of specific frequencies of MNS on food-related attention and appetite. The experiment used an odourised, dot probe task for testing food-related attention and a combination of behavioural (i.e., visual analogue scales; VAS) and physiological approaches (i.e., electrocardiograph; ECG - root mean square of successive differences between normal heartbeats-RMSSD: parasympathetic nervous system activation (RMSSD), stress index-SI: sympathetic nervous system activation) for measuring hunger, appetite, and satiation. Twenty-four healthy, male adults completed a VAS and dot probe task before and after receiving either 40 Hz-, 80 Hz-, 120 Hz MNS or sham (control) across four different sessions with continuous ECG recording throughout each session. Data from the dot probe task were analysed using repeated-measures ANOVA, while pair-wise tests were used for ECG recordings and VAS. Improvements on the dot probe task, not specific to odour-food congruence were found after 40 Hz MNS (p-value = 0.048; strong effect size (0.308 partial eta squared)) while increased ratings of hunger (VAS) (p-value = 0.03, small effect size (0.47 Cohen-D)) and RMSSD scores (p-value < 0.001; medium effect size (0.76 Cohen-D)) were found after 120 Hz MNS. These findings implore further testing of MNS frequency parameters on improving RMSSD, a characteristic marker of measuring parasympathetic/autonomic nervous system activation pertaining to the vagal network. Furthermore, improving sympathovagal balance is associated with cardiovascular benefits in numerous health-related conditions such as obesity, hypertension and diabetes.

Investigation of the Optimal Parameters of Median Nerve Stimulation Using a Variety of Stimulation Methods and Its Effects on Heart Rate Variability: A Systematic Review.

OBJECTIVES: There is a wealth of literature supporting the use of median nerve stimulation (MNS) for modulating autonomic nervous system (ANS) dysfunction such as in hypoxia, recovery after heart valve replacement, ischemia, and cardiac contractibility. Heart rate variability (HRV) is considered a gold standard for measuring autonomic modulation and dynamic nonlinear ANS processes through the use of an electrocardiogram (ECG). Although the use of MNS on HRV in animals and humans has been documented, optimal stimulation parameters are yet to be outlined. MATERIALS AND METHODS: This review aims to synthesize findings of neurostimulation using MNS on animals and humans while observing HRV using an ECG. Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with search parameters of "Median nerve stimulation," "Neiguan," "PC-6," "HRV," "Heart rate variability," and "Heart-rate variability" observing on animals and human subjects, we found a total of 17 eligible articles. RESULTS: In this review, changing two parameters, that is, stimulation frequency and side of stimulation, appears to be the most influential in effecting frequency-domain ECG analysis of HRV. However, it is evident from this review that to perform an effective comparison of the effects of MNS on HRV, more detailed reports of the studies are required. CONCLUSIONS: Finding the optimal stimulation parameters for MNS is crucial for improving HRV. This will in turn contribute to normalizing ANS function impaired in numerous clinical conditions, such as epilepsy or diabetes.

Non-contact neuromodulation of the human autonomic nervous system function via different odors: Sex, menstrual cycle, and odor dose- and duration-specific effects.

In recent decades, it has been uncovered that the autonomic nervous system (ANS) can be influenced using non-contact neuromodulation via odor stimulation. Increasing parasympathetic-vagal activation of the ANS is integral to improving the sympathovagal balance between the sympathetic- and parasympathetic nervous systems, which is often imbalanced in several chronic inflammatory disorders, such as rheumatoid arthritis and inflammatory bowel diseases. Although research into olfactory stimulation has been observed on the ANS, it is still lacking in the exploration of odor concentration and odor-specific effects. This is particularly the case as research has not utilized specified tools, such as the olfactometer to provide precise odor delivery. Furthermore, no research has compared the results in separate sex cohorts to investigate the role of sex or the menstrual stage on the subsequent interactions. In this study, we investigated the olfactory stimulation effects of four natural odors (mushroom, lavender, jasmine, and rose) in three concentrations (low, moderate, and high) on the ANS. To observe activity from the ANS, we used an electrocardiogram (ECG) based heart rate variability (HRV) and eye-tracker technology (pupil diameter). We found for the first time in literature that there were acute dose- and duration-specific odor effects of odors on the ANS. We also found sex and menstrual cycle effects in this interaction. Furthermore, there were stark distinctions in sympathovagal activity dependent ANS activation (HRV) in comparison to the oculomotor nerve-parasympathetic/cervical sympathetic nerves dependent ANS responses (pupil diameter). Sympathovagal activity dependent HRV showed odor, sex, and menstrual-stage interactions in both divisions of the ANS while the pupil responses only indicated increased sympathetic activation. These results shed light on the use of odor-specific stimulation to modulate the ANS activity in the context of sex and the menstrual stage. Future studies should be performed using a chronic odor delivery design to investigate the long-term effects of odors on the ANS. Clinical trial registration: Australian New Zealand Clinical Trials Registry, identifier [ACTRN12622000415707].

Non-invasive High Frequency Median Nerve Stimulation Effectively Suppresses Olfactory Intensity Perception in Healthy Males.

Median nerve stimulation (MNS) had been performed in the existing literature to alleviate symptoms of nausea and vomiting. The observed facilitative effects are thought to be mediated by the vagal pathways, particularly the vagus nerve (VN) brainstem nuclei of the dorsal motor nucleus of vagus and nucleus tractus solitarius (DMV-NTS). Sense of smell is one of the major sensory modalities for inducing vomiting and nausea as a primary defense against potentially harmful intake of material. This study aimed to test effects of non-invasive, high and low frequency MNS on human olfactory functioning, with supplementary exploration of the orbitofrontal cortex (OFC) using near-infrared spectroscopy (NIRS). Twenty healthy, male, adults performed supra-threshold odor intensity tests (labeled magnitude scale, LMS) for four food-related odorant samples (presented in three different concentrations) before and after receiving high-, low frequency MNS and placebo (no stimulation), while cortical activities in the OFC was monitored by the NIRS. Data of the NIRS and LMS test of separate stimulation parameters were statistically analyzed using mixed-model analysis of variance (ANOVA). Only the high frequency MNS showed effects for suppressing the intensity perception of the moderate concentration of Amyl Acetate (p:0.042) and strong concentration of Isovaleric Acid (p:0.004) and 1-Octen-3-ol (p:0.006). These behavioral changes were coupled with significant changes in the NIRS recordings of the left (p:0.000) and right (p:0.003) hemispheric orbitofrontal cortices. This is the first study that applied non-invasive, high frequency MNS to suppress the supra-threshold odor ratings of specific concentrations of odors. The vagal networks are potential relays of MNS to influence OFC. Results from the current article implore further research into non-invasive, high frequency MNS in the investigation of its modulatory effects on olfactory function, given its potential to be used for ameliorating nausea and malnutrition associated with various health conditions.

Improvement of Olfactory Function With High Frequency Non-invasive Auricular Electrostimulation in Healthy Humans.

In past literature on animal models, invasive vagal nerve stimulation using high frequencies has shown to be effective at modulating the activity of the olfactory bulb (OB). Recent advances in invasive vagal nerve stimulation in humans, despite previous findings in animal models, used low frequency stimulation and found no effect on the olfactory functioning. The present article aimed to test potential effects of non-invasive, high and low frequency vagal nerve stimulation in humans, with supplementary exploration of the orbitofrontal cortex using near-infrared spectroscopy (NIRS). Healthy, male adult participants (n = 18) performed two olfactory tests [odor threshold test (OTT) and supra-threshold test (STT)] before and after receiving high-, low frequency vagal nerve stimulation and placebo (no stimulation). Participant's olfactory functioning was monitored using NIRS, and assessed with two behavioral olfactory tests. NIRS data of separate stimulation parameters were statistically analyzed using repeated-measures ANOVA across different stages. Data from olfactory tests were analyzed using paired parametric and non-parametric statistical tests. Only high frequency, non-invasive vagal nerve stimulation was able to positively modulate the performance of the healthy participants in the STT (p = 0.021, Wilcoxon sign-ranked test), with significant differences in NIRS (p = 0.014, post-hoc with Bonferroni correction) recordings of the right hemispheric, orbitofrontal cortex. The results from the current article implore further exploration of the neurocircuitry involved under vagal nerve stimulation and the effects of non-invasive, high frequency, vagal nerve stimulation toward olfactory dysfunction which showcase in Parkinson's and Alzheimer's Diseases. Despite the sufficient effect size (moderate effect, correlation coefficient (r): 0.39 for the STT) of the current study, future research should replicate the current findings with a larger cohort.

Spared motivational modulation of cognitive effort in a maternal immune activation model of schizophrenia risk.

Maternal immune activation (MIA) during gestation is a significant risk factor for development of schizophrenia and other neurodevelopmental diseases. In animal models of this risk factor, MIA during pregnancy can produce offspring that recapitulate certain aspects of the behavioral and neurophysiological impairments seen in schizophrenia. Here, the authors tested the effect of polyinosinic-polycytidylic acid (poly I:C)-induced MIA in a task that explicitly assays the interaction between motivation and cognition. In our paradigm, discrimination accuracy during a sustained-attention task is differentially impacted by environmental cues that signal the probability of reward for accurate performance. Cognition-motivation interactions are implicated in producing functional impairments in patients. Therefore, to the extent that this MIA model recapitulates such impairments, the authors predicted impaired ability of reward-associated signals to modulate cognitive performance in MIA rat offpsring. Adult offspring of dams in which MIA was induced displayed impaired prepulse inhibition relative to controls, verifying a functional effect of poly I:C induction. Despite this deficit, there were no differences between MIA and control rats in any aspects of task learning or performance, including under extinction and reacquisition conditions. These results indicate that MIA spares functioning of some of the cognitive, motivational, and decision-making processes that are impacted in schizophrenia and suggest that MIA as an isolated manipulation does not model the full range and nuance of the cognitive and motivational impairments in the disease. The authors suggest that some aspects of the functional impairment in schizophrenia and other neurodevelopmental diseases may be better modeled using multiple "hit" models of disease risk. (PsycINFO Database Record