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Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

ABSTRACT: Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental sessions on different days: (1) tVNS and (2) control. Using a tVNS device, an auricular electrode was placed on the left cymba conchae of the external ear; an electric current with a pulse frequency of 25 Hz and amplitude between 1 and 6 mA was applied. For the assessment of ANS, the beat-to-beat HR and systolic arterial pressure (SAP) were analyzed using linear and nonlinear approaches during clinostatic and orthostatic conditions. In clinostatic conditions, tVNS reduced HR (p < 0.01), SAP variability (p < 0.01), and cardiac and peripheral sympathetic modulation (p < 0.01). The responsivity of the peripheral sympathetic modulation to orthostatic stress during tVNS was significantly higher when compared to the control session (p = 0.03). In conclusion, tVNS reduces the HR and affects cardiac and peripheral autonomic control and increases the responses of peripheral autonomic control to orthostatic stress in healthy subjects.

SUBMITTER: Tobaldini E

PROVIDER: S-EPMC6517949 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

Tobaldini Eleonora E Toschi-Dias Edgar E Appratto de Souza Liliane L Rabello Casali Karina K Vicenzi Marco M Sandrone Giulia G Cogliati Chiara C La Rovere Maria Teresa MT Pinna Gian Domenico GD Montano Nicola N

Journal of clinical medicine 20190411 4

Previous studies showed that transcutaneous vagus nerve stimulation (tVNS) modulates the autonomic nervous system (ANS) in resting condition. However, the autonomic regulation in response to an orthostatic challenge during tVNS in healthy subjects remains unknown. We tested the hypothesis that tVNS reduces heart rate (HR) and alters the responsivity of ANS to orthostatic stress in healthy subjects. In a randomized and cross-over trial, thirteen healthy subjects underwent two experimental session ...[more]

PMID: 30979068

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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:IntroductionAuricular low-level transcutaneous vagus nerve stimulation (aLL-tVNS) has emerged as a promising technology for cardiac arrhythmia management but is still experimental. In this physiological study, we hypothesized that aLL-tVNS modulated the autonomic nervous balance through a reduction of sympathetic tone and an increase in heart rate variability (HRV). We investigated the muscle sympathetic nerve activity (MSNA) recorded by microneurography during vagally mediated aLL-tVNS and active control on healthy volunteers.MethodsIn this crossover, double-blind controlled study, healthy men (N = 28; 27 ± 4 years old) were assigned to aLL-tVNS applied to cymba and lobe (active control) of the right ear. Each participant was randomly allocated to the three sequences (5 Hz, 20 Hz, and active control-5 Hz) during one session. MSNA signal was recorded at rest, during voluntarily apnea and aLL-tVNS. Sympathetic activity was expressed as: 1) number of bursts per minute (burst frequency, BF) and 2) MSNA activity calculated as BF x mean burst amplitude and expressed as changes from baseline (%). RR intervals, HRV parameters and sympathetic activity were analyzed during 5 min-baseline, 10 min-stimulation, and 10 min-recovery periods. Mixed regression models were performed to evaluate cymba-(5-20 Hz) effects on the parameters with stimulation.ResultsDuring apnea and compared to baseline, BF and MSNA activity increased (p = 0.002, p = 0.001, respectively). No stimulation effect on RR intervals and HRV parameters were showed excepted a slightly increase of the LF/HF ratio with stimulation in the cymba-5Hz sequence (coef. ± SE: 0.76 ± 0.32%; p = 0.02). During stimulation, reductions from baseline in BF (Coef. ± SE: -4.8 ± 1.1, p < 0.001) was observed but was not statistically different from that one in the active control. Reduction of MSNA activity was not significantly different between sequences.ConclusionAcute right cymba aLL-tVNS did not induce any overall effects neither on heart rate, HRV nor MSNA variables on healthy subjects when compared to active control. Interestingly, these findings questioned the role of active controls in medical device clinical trials that implied subjective endpoints.

Dataset Information

Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

Publications

Cardiac and Peripheral Autonomic Responses to Orthostatic Stress During Transcutaneous Vagus Nerve Stimulation in Healthy Subjects.

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