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Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

ABSTRACT: Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate weight loss and improve glucose tolerance if taVNS were applied chronically. In two single-blinded randomized cross-over protocols, blood glucose levels, plasma concentrations of insulin, C-peptide, glucagon, leptin, and ghrelin, together with heart rate variability and baroreceptor-heart rate reflex sensitivity were determined before and after taVNS (left ear, 10 Hz, 300 µs, 2.0-2.5 mA, 30 min) or sham-taVNS (electrode attached to ear with the stimulator turned off). In a first protocol, subjects (n = 16) were fasted throughout the protocol and in a second protocol, subjects (n = 10) received a high-calorie beverage (220 kCal) after the first blood sample, just before initiation of taVNS or sham-taVNS. No significant effects of taVNS on heart rate variability and baroreceptor-heart rate reflex sensitivity and only minor effects on glucotropic hormones were observed. However, in the second protocol taVNS significantly lowered postprandial plasma ghrelin levels (taVNS: -115.5 ± 28.3 pg/ml vs. sham-taVNS: -51.2 ± 30.6 pg/ml, p < 0.05). This finding provides a rationale for follow-up studies testing the hypothesis that chronic application of taVNS may reduce food intake through inhibition of ghrelin and, therefore, may indirectly improve glucose tolerance through weight loss.

SUBMITTER: Kozorosky EM

PROVIDER: S-EPMC9020171 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

Kozorosky Erica M EM Lee Cristina H CH Lee Jessica G JG Nunez Martinez Valeria V Padayachee Leandra E LE Stauss Harald M HM

Physiological reports 20220401 8

Vagus nerve stimulation (VNS) facilitates weight loss in animals and patients treated with VNS for depression or epilepsy. Likewise, chronic transcutaneous auricular VNS (taVNS) reduces weight gain and improves glucose tolerance in Zucker diabetic fatty rats. If these metabolic effects of taVNS observed in rats translate to humans is unknown. Therefore, the hypothesis of this study was that acute application of taVNS affects glucotropic and orexigenic hormones which could potentially facilitate ...[more]

PMID: 35441808

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Project description:ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) modulates brain activity and heart function. The induced parasympathetic predominance leads to an increase of heart rate variability (HRV). Knowledge on the corresponding cortical activation pattern is, however, scarce. We hypothesized taVNS-induced HRV increases to be related to modulation of cortical activity that regulates the autonomic outflow to the heart.Materials and methodsIn thirteen healthy subjects, we simultaneously recorded 64-channel electroencephalography and electrocardiography during taVNS. Two taVNS stimulation targets were investigated, i.e., the cymba conchae and inner tragus, and compared to active control stimulation in the anatomical vicinity, i.e., at the crus helicis and outer tragus. We used intermitted stimulation bursts of 25 Hz applied at a periodicity of 1 Hz. HRV was estimated with different time-domain methodologies: standard deviation of RR (SDNN), the root mean squares of successive differences (RMSSD), the percentage of RR-intervals with at least 50 ms deviation from the preceding RR-interval (pNN50), and the difference of consecutive RR intervals weighted by their mean (rrHRV).ResultsThe stimulation-induced HRV increases corresponded to frequency-specific oscillatory modulation of different cortical areas. All stimulation targets induced power modulations that were proportional to the HRV elevation. The most prominent changes that corresponded to HRV increases across all parameters and stimulation locations were frontal elevations in the theta-band. In the delta-band, there were frontal increases (RMSSD, pNN50, rrHRV, SDNN) and decreases (SDNN) across stimulation sites. In higher frequencies, there was a more divers activity pattern: Outer tragus/crus helicis stimulation increased oscillatory activity with the most prominent changes for the SDNN in frontal (alpha-band, beta-band) and fronto-parietal (gamma-band) areas. During inner tragus/cymba conchae stimulation the predominant pattern was a distributed power decrease, particularly in the fronto-parietal gamma-band.ConclusionNeuro-cardiac interactions can be modulated by electrical stimulation at different auricular locations. Increased HRV during stimulation is correlated with frequency-specific increases and decreases of oscillatory activity in different brain areas. When applying specific HRV measures, cortical patterns related to parasympathetic (RMSSD, pNN50, rrHRV) and sympathetic (SDNN) modulation can be identified. Thus, cortical oscillations may be used to define stimulation locations and parameters for research and therapeutic purposes.

Project description:ImportanceEvidence from randomized clinical trials of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia disorder is lacking.ObjectiveTo evaluate the efficacy and safety of taVNS for chronic insomnia compared with the sham taVNS.Design, setting, and participantsThis randomized clinical trial was conducted from October 2021 to December 2022 at a single center in Beijing, China. Patients with chronic insomnia disorder with a Pittsburgh Sleep Quality Index (PSQI) of at least 8 were enrolled. Statistical analysis was performed from June to September 2023.InterventionsPatients were allocated to the active taVNS group or sham taVNS group with a 1:1 ratio. Both groups received the stimulation for 30 minutes each time, twice a day, 5 consecutive days a week, with an 8-week treatment and a 12-week follow-up.Main outcomes and measuresThe primary end point was the mean change from baseline through week 8 in PSQI scores. Minimal clinically important difference was 2.5 points. Secondary outcomes included mental health, sleepiness, and fatigue. Safety was also evaluated.ResultsA total of 72 participants were randomized to either active taVNS group (36 participants; mean [SD] age, 45.2 [14.5] years; 27 [75.0%] female) or the sham taVNS group (36 participants; mean [SD] age, 44.6 [13.9] years; 31 [86.1%] female); 68 participants completed the 8-week intervention. The least-square mean changes from baseline to week 8 in PSQI were -8.2 (95% CI, -9.3 to -7.0) points in the taVNS group and -3.9 (95% CI, -5.1 to -2.7) points in the sham group. Both groups experienced statistically significant improvements from before to after the intervention. However, active taVNS showed a clinically meaningful 4.2-point greater reduction (95% CI, -5.9 to -2.6 points; P < .001; Cohen d effect size, 1.2) in PSQI compared with the sham group (minimal clinically important difference = 2.5 points). Secondary outcomes, including mental health and fatigue, showed similar favorable results. The efficacy of taVNS was sustained throughout the 20-week study period.Conclusions and relevanceIn this randomized clinical trial, taVNS significantly reduced insomnia severity. Clinically meaningful enhancements in PSQI scores were observed compared with sham stimulation, with the benefits of taVNS sustained over a 20-week period. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness across diverse populations.Trial registrationChinese Clinical Trial Registry: ChiCTR2100051319.

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Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

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Transcutaneous auricular vagus nerve stimulation augments postprandial inhibition of ghrelin.

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