Frequency-dependent Effects of Respiratory-Gated Auricular Vagal Nerve Stimulation in the Modulation of Mood and Anxiety Symptoms in Major Depression

Colleen Sheller, BS

Massachusetts General Hospital – Research Assistant

Scientific Abstract


Recent studies have suggested that a novel neuromodulation technique called respiratory-gated transcutaneous vagus nerve stimulation (RAVANS), which electrically stimulates the auricular branch of the vagus nerve (ABVN), may effectively modulate the stress response circuitry and have beneficial effects on stress response and mood and anxiety regulation in patients with major depressive disorder (MDD). However, optimal stimulation parameters for this technique have not been established.  The aim of this study was to identify potential frequency-dependent effects of RAVANS on the regulation depressed mood and anxiety symptoms in patients with MDD.   


For preliminary analyses, we report here on the first eleven women (30.0 ± 6.2 yrs) with recurrent MDD and in an active episode included in the study. Subjects underwent five stimulation sessions, during which they received exhalatory-gated stimulation at frequencies of 2, 8, 30, and 100 Hz or sham stimulation, in a randomized order. Electrodes were placed over vagal-innervated auricular regions (cymba concha) in the left ear, and stimulation amplitude was calibrated to an intensity that produced a moderate, non-painful sensation. Subjects completed self-report mood questionnaires including the Beck’s Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) at the beginning and end of each stimulation session.


RAVANS administration at a 100 Hz frequency was associated with a significant reduction from baseline in BDI scores (26.7 ± 12.2 vs 29.6 ± 11.3, p=0.04) and STAI scores (42.7 ± 9.7 vs 48.6 ± 13.5, p=0.01). The reduction in STAI scores in the 100 Hz session showed a trend toward significance when compared to Sham (-5.9 ± 6.3 vs -0.27 ± 7.7, p=0.07). No significant effects were identified for other stimulation frequencies.


These preliminary results suggest that RAVANS administration at a higher frequency could be more effective on the modulation of mood and anxiety symptoms in MDD patients. Future

Longitudinal studies should evaluate the potential effects of these optimized intervention in the management of major depression.

Live Zoom Session – March 9th

research Areas


Colleen Sheller, B.S., Rachel Staley, B.S., Harlyn Aizley, Ed.M., Riccardo Barbieri, Ph.D., Vitaly Napadow, Ph.D., David Mischoulon, M.D., Ph.D., Jill M. Goldstein, Ph.D., Ronald G. Garcia, M.D., Ph.D.

Principal Investigator

Ronald Garcia Gomez, M.D.,Ph.D.

Affiliated Website