Autonomic and neural responses to varying transcutaneous cervical electrical stimulation parameters

Transcutaneous cervical electrical stimulation (TCES) offers a noninvasive approach to modulate the autonomic nervous system (ANS), but optimal stimulation parameters remain undefined. This pilot study aimed to identify optimal TCES parameters by evaluating autonomic and neural responses across varying frequencies, current intensities, electrode montages, and durations, using heart rate variability (HRV) and electroencephalography (EEG) alpha-band power as biomarkers of parasympathetic activity.

Twenty healthy adults completed four testing sessions, each examining one stimulation parameter. Autonomic data were collected including electrocardiography, non-invasive blood pressure, pupillometry, photoplethysmography, and dry-electrode EEG. Four frequencies (10, 25, 40, 150 Hz), three current intensities (sub-sensation threshold, sensation threshold, supra-sensation threshold), three electrode montages (bilateral, left-only, right-only), and two durations (4, 20 min) were tested. Root mean square of successive differences (RMSSD) and global EEG alpha-band power were primary outcomes. Parameters were sequentially optimized across visits based on individual RMSSD responses.

No single frequency produced a significantly higher RMSSD or alpha-band power response. However, each participant exhibited a personalized preferred frequency yielding a mean 41% RMSSD increase in visit 1. This individualized frequency was selected for further visits varying current intensity and electrode montage. Supra-sensation threshold intensity was most effective, with 60% of participants responding strongest at this level. Left-sided stimulation resulted in a decrease in both RMSSD and alpha-band power, while right-sided and bilateral montages resulted in similar increases for these biomarkers. Due to decreasing cardiac vagal response in successive sessions, the preferred frequency was reevaluated before testing duration. The mean RMSSD response increased 54% upon recalibration in visit 4, though the preferred frequency shifted in 75% of participants. Autonomic vitals did not significantly modulate more with longer stimulation duration; pulse rate variability during 20-min stimulation revealed oscillatory autonomic dynamics with peak parasympathetic responses emerging around 4 min.

TCES can modulate cardiac vagal and cortical responses as measured by RMSSD and EEG alpha-band power, respectively, and a personalized, biomarker-guided approach to TCES parameter optimization is essential for future clinical applications targeting autonomic dysfunction.

This study was registered with Clinicaltrials.gov, identifier NCT04100486, on September 16, 2019.