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Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review.

ABSTRACT: BACKGROUND:Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters. OBJECTIVE:We developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation. METHODS:We enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500??s 25?HZ for 60?s (repeated 3 times over 6?min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted. RESULTS:Active stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate. CONCLUSION:Stimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.

SUBMITTER: Badran BW

PROVIDER: S-EPMC6487660 | biostudies-literature | 2018 May - Jun

REPOSITORIES: biostudies-literature

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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:Implanted vagus nerve stimulation (VNS) delivered concurrently with upper limb rehabilitation has been shown to improve arm function after stroke. Transcutaneous auricular VNS (taVNS) offers a non-invasive alternative to implanted VNS and may provide similar therapeutic benefit. There is much discussion about the optimal approach for combining VNS and physical therapy, as such we sought to determine whether taVNS administered during robotic training, specifically delivered during the premotor planning stage for arm extension movements, would confer additional motor improvement in patients with chronic stroke. Thirty-six patients with chronic, moderate-severe upper limb hemiparesis (>6 months; mean Upper Extremity Fugl-Meyer score = 25 ± 2, range 13-48), were randomized to receive 9 sessions (1 h in length, 3x/week for 3 weeks) of active (N = 18) or sham (N = 18) taVNS (500 ms bursts, frequency 30 Hz, pulse width 0.3 ms, max intensity 5 mA, ∼250 stimulated movements per session) delivered during robotic training. taVNS was triggered by the onset of a visual cue prior to center-out arm extension movements. Clinical assessments and surface electromyography (sEMG) measures of the biceps and triceps brachii were collected during separate test sessions. Significant motor improvements were measured for both the active and sham taVNS groups, and these improvements were robust at 3 month follow-up. Compared to the sham group, the active taVNS group showed a significant reduction in spasticity of the wrist and hand at discharge (Modified Tardieu Scale; taVNS = -8.94% vs. sham = + 2.97%, p < 0.05). The EMG results also demonstrated significantly increased variance for the bicep peak sEMG amplitude during extension for the active taVNS group compared to the sham group at discharge (active = 26.29% MVC ± 3.89, sham = 10.63% MVC ± 3.10, mean absolute change admission to discharge, p < 0.01), and at 3-month follow-up, the bicep peak sEMG amplitude was significantly reduced in the active taVNS group (P < 0.05). Thus, robot training improved the motor capacity of both groups, and taVNS, decreased spasticity. taVNS administered during premotor planning of movement may play a role in improving coordinated activation of the agonist-antagonist upper arm muscle groups by mitigating spasticity and increasing motor control following stroke. Clinical Trial Registration: www.ClinicalTrials.gov, identifier (NCT03592745).

Project description:Background Although the coronavirus disease 19 (COVID-19) pandemic has now impacted the world for over two years, the persistent secondary neuropsychiatric effects are still not fully understood. These "long COVID" symptoms, also referred to as post-acute sequelae of SARS-CoV-2 infection (PASC), can persist for months after infection without any effective treatments. Long COVID involves a complex heterogenous symptomology and can lead to disability and limit work. Long COVID symptoms may be due to sustained inflammatory responses and prolonged immune response after infection. Interestingly, vagus nerve stimulation (VNS) may have anti-inflammatory effects, however, until recently, VNS could not be self-administered, at-home, noninvasively. Methods We created a double-blind, noninvasive transcutaneous auricular VNS (taVNS) system that can be self-administered at home with simultaneous remote monitoring of physiological biomarkers and video supervision by study staff. Subsequently, we carried out a pilot (n = 13) randomized, sham-controlled, trial with this system for four weeks to treat nine predefined long covid symptoms (anxiety, depression, vertigo, anosmia, ageusia, headaches, fatigue, irritability, brain fog). No in-person patient contact was needed, with informed consent, trainings, ratings, and all procedures being conducted remotely during the pandemic (2020-2021) and equipment being shipped to individuals' homes. This trial was registered onClinicalTrials.gov under the identifier: NCT04638673. Results Four-weeks of at-home self-administered taVNS (two, one-hour sessions daily, delivered at suprathreshold intensities) was feasible and safe. Although our trial was not powered to determine efficacy as an intervention in a heterogenous population, the trends in the data suggest taVNS may have a mild to moderate effect in reducing mental fatigue symptoms in a subset of individuals. This innovative study demonstrates the safety and feasibility of supervised self-administered taVNS under a fully contactless protocol and suggests that future studies can safely investigate this novel form of brain stimulation at-home for a variety of neuropsychiatric and motor recovery applications.

Project description:BackgroundDepression accompanying chronic pain (CP) is one of the most common comorbid psychiatric disorders. This study aimed to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) combined with electroacupuncture at Baihui (GV20) and Yintang (GV29) acupoints compared with citalopram.MethodsSixty patients with depression and pain comorbidity were enrolled in a prospective 8-week, single-blind, randomized controlled trial. Participants were randomly assigned to receive either taVNS combined with electroacupuncture treatment (taVNS: 8 weeks, 3 sessions per week; electroacupuncture: 8 weeks, twice per day, no drugs) or citalopram treatment (8 weeks, 40 mg/day). The primary outcome was Montgomery-Åsberg Depression Rating Scale (MADRS). The secondary endpoints were evaluated using the McGill Pain Questionnaire (SF-MPQ), self-reported 36-Item Short Form Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD) and Hamilton Anxiety Scale (HAMA).ResultsBoth the taVNS combined with electroacupuncture and citalopram groups had significant reductions in depressive and pain symptoms, as indicated by the decrease in MARDS and SF-MPQ scores. Regarding the analgesic effect, the pain intensity score of the SF-MPQ showed a larger reduction with citalopram than with taVNS combined with electroacupuncture at 6 weeks (P = 0.036). The reduction in the BP score of the SF-36 was higher at week 4 (P = 0.000), with no significant difference observed at week 8 (P = 0.1110). This result indicated that the pain intensity can be improved rapidly with citalopram compared with taVNS combined with electroacupuncture. Similarly, the comparison of PSQI scores at 4, 6, and 8 weeks indicates that there was no significant difference between groups, except in the use of sleeping medications. At week 6, higher medication use was found in the citalopram group than in the taVNS combined with electroacupuncture group (P = 0.049).ConclusionIn summary, compared with citalopram, taVNS combined with electroacupuncture produces similar positive effects on depressive and pain symptoms in patients with depression and chronic pain, which last for at least 8 weeks.

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Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review.

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