What question did this study set out to answer?

The study aims to evaluate the effects of transcutaneous vagus nerve stimulation and neurofeedback on cortisol levels, anxiety, and depression in non-clinical adults.

January 10, 2026Applied Psychophysiology and Biofeedback0 citationsOpen Access

Effects of Transcutaneous Vagus Nerve Stimulation, Neurofeedback, and their Combination on Cortisol, Anxiety, and Depression Subtypes in Non-Clinical Adults

SMSeyedeh Zeinab MolaeizadehUniversity of the Basque Country AAAitor AritzetaUniversity of the Basque Country ZZZahra ZolghadrShahid Beheshti University of Medical Sciences

Key Points

The study aims to evaluate the effects of transcutaneous vagus nerve stimulation and neurofeedback on cortisol levels, anxiety, and depression in non-clinical adults.
Randomized controlled trial design

Structured PICO

Does neurofeedback, transcutaneous vagus nerve stimulation, or their combination improve anxiety, depression, EEG Alpha/Theta ratio, and salivary cortisol in healthy young adults?

Population

20 healthy medication-free university students (19 females, 1 male) aged 18–24 years, with no history of neurological, cardiovascular, or psychiatric conditions.

Intervention

Neurofeedback (NF) targeting Alpha/Theta rhythms, transcutaneous vagus nerve stimulation (tVNS) at 20 Hz, or their combination (NF + tVNS), delivered twice weekly for 30-60 min over four weeks.

Comparator

Waitlist control group undergoing pre- and post-intervention assessments without active intervention.

Outcome

Changes in anxiety (Beck Anxiety Inventory), depression subtypes (MCMI-IV), EEG Alpha/Theta ratio, and morning salivary cortisol from pre- to post-intervention.patient reported

In a small pilot study of healthy adults, neurofeedback improved self-reported anxiety and depression, while transcutaneous vagus nerve stimulation modulated EEG Alpha/Theta ratios, suggesting distinct top-down and bottom-up mechanisms.

Abstract

Non-invasive neuromodulation techniques such as neurofeedback (NF) and transcutaneous vagus nerve stimulation (tVNS) are attracting growing interest for their potential to influence brain activity and emotional regulation. This pilot study investigated the individual and combined effects of these methods on psychological measures, electrophysiological markers, and salivary cortisol. Twenty healthy young adults (19 females, 1 male, aged 18–24) participated, with outcomes including psychological measures (anxiety and depression), EEG Alpha / Theta ratio, and salivary cortisol. NF was associated with significant reductions in anxiety and depressive symptoms. Notably, despite the NF protocol directly targeting Alpha / Theta oscillations, a significant increase in the Alpha / Theta ratio was observed only in the tVNS group, indicating a distinct bottom-up influence on neural dynamics. The combined intervention did not yield additional benefits, and cortisol levels remained unchanged. These preliminary findings suggest that NF and tVNS may operate through distinct pathways—NF influencing psychological outcomes via top-down regulation and tVNS modulating electrophysiological activity via bottom-up pathways. The absence of sham control conditions limits causal attribution of effects. Given the small sample size (n = 5 per group) and exploratory nature of this study, these results should be interpreted as hypothesis-generating and require replication in larger, adequately powered trials.

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