Transcutaneous auricular vagus nerve stimulation and heart rate variability: Analysis of parameters and targets.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (taVNS) modulates central and peripheral neurophysiology. Specifically, taVNS increases heart rate variability (HRV) indicating a shift in autonomic function towards parasympathetic predominance. However, knowledge on the influence of stimulation parameters and targets is scarce. We hypothesized that the location and charge per phase of taVNS influences HRV. MATERIALS AND METHODS: In thirteen healthy subjects, six different stimulation targets were investigated, i.e., cymba conchae, cavum conchae, outer tragus, inner tragus, crus helicis, and fossa triangularis. At each target, 24 parameter combinations were studied: Eight different electrical charges per phase were evaluated by investigating three pulse durations and eight charge-balanced current intensities, i.e., 100 µs (0.250-2 mA in steps of 0.250 mA), 260 µs (0.096-0.769 mA in steps of 0.096 mA), and 500 µs (0.050-0.400 mA in steps of 0.050 mA). In a parallel group design, left and right taVNS were compared to each other. 30 bursts at each parameter combination were applied with a periodicity of 1 Hz. Each burst consisted of five pulses applied at 25 Hz. RESULTS: HRV increased in a charge-dependent way with significant differences between the right and left ear. The targets with the strongest effects were the cymba conchae and fossa triangularis, and to a lesser extent the inner tragus. CONCLUSIONS: HRV is suitable to define taVNS parameters and targets for research and therapeutic purposes. Bursts of taVNS with a pulse duration of 100 µs and a current intensity of 2 mA are comfortable for the participants and effective in increasing HRV when applied at specific auricular locations. These findings need to be replicated in larger cohorts, and with longer stimulation and off-periods between conditions. Since results may differ in conditions with an impaired autonomic tone, future studies should also consider aged and patient populations.

Brain-Heart Interaction During Transcutaneous Auricular Vagus Nerve Stimulation.

OBJECTIVES: Transcutaneous 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 METHODS: In 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). RESULTS: The 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. CONCLUSION: Neuro-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.

Neuro-cardiac coupling predicts transcutaneous auricular vagus nerve stimulation effects.

BACKGROUND: Transcutaneous auricular Vagus Nerve Stimulation (taVNS) is a non-invasive neuromodulation technique that may constitute an effective treatment for a wide range of neurological, psychiatric, and medical conditions. One key challenge in taVNS research is the high interindividual response variability. To gain an understanding of this variability, reliable biomarkers for taVNS responsiveness would be highly desirable. In this study, we investigated physiological candidate biomarkers while systematically varying stimulation conditions and observing physiological state characteristics. METHODS: Forty-four healthy young adults received taVNS and sham-stimulation. Subjects were pseudo-randomly assigned to stimulation of the left or right ear. Each subject underwent six blocks of stimulation. Across blocks, respiration-locking (inhalation-locked taVNS vs. exhalation-locked taVNS vs. sham) and the electrode location (tragus vs. cymba conchae) were varied. We analyzed heart rate (HR), various heart rate variability (HRV) scores, and neuro-cardiac coupling (NCC), indexed by the relationship between electroencephalographic delta power and heartbeat length. RESULTS: We observed an effect of taVNS on HR and HRV scores during, but not after stimulation. The direction of the effects was consistent with parasympathetic activation. We did not observe any systematic influence of the stimulation conditions that we varied. However, we found baseline NCC scores to be significant predictors for the individual effect of taVNS on HRV scores. CONCLUSION: Cardiac effects of taVNS indicate parasympathetic activation. These effects were short lived, which might explain that some previous studies were unable to detect them. We propose NCC as a novel candidate biomarker for responsiveness to taVNS.