Effects of Transcutaneous Auricular Vagus Nerve Stimulation on Cognitive Performance and Sex Differences

Bahçeşehir University

Status: Not yet enrolling

Conditions: Sex Differences; Healthy Participants; Executive Functions; Vagus Nerve Stimulation; Cognitive Assessment; taVNS; Cognition; Neuromodulation

Treatments: Device: Active taVNS; Device: Sham Stimulation

Study type: Interventional

Funder types: Other

Identifiers

NCT07256080

61351342/020-93

Details and patient eligibility

About

This study investigates the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cognitive performance in healthy adults. The study uses a sham-controlled, cross-over design in which each participant receives both active taVNS and sham stimulation in separate sessions. Each participant completes both conditions (active and sham) in a randomized order using a crossover design. Cognitive performance will be assessed before and after each session using standardized tests. The study also explores whether males and females respond differently to taVNS, in order to identify potential sex-related differences in cognitive outcomes.

Full description

This randomized, sham-controlled cross-over study investigates the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cognitive performance, autonomic activity, and psychological state in healthy young adults, with specific attention to sex differences. Because hormonal fluctuations may influence vagal tone and cognitive outcomes, female participants are required to complete their stimulation sessions during the follicular phase (Day 5-10) of the menstrual cycle. Male participants follow the same protocol without timing restrictions.

The study consists of three laboratory visits, scheduled one week apart.

Visit 1 (Baseline Assessments):

Participants provide informed consent and complete a demographic questionnaire, menstrual-cycle verification (for female participants), the Montreal Cognitive Assessment (MoCA), and baseline psychological questionnaires including the State-Trait Anxiety Inventory (STAI) and the Perceived Stress Scale (PSS). Baseline cognitive performance is measured using the CogniFit digital battery.

Visits 2 and 3 (Randomized Cross-Over Stimulation Sessions):

Participants undergo active taVNS and sham stimulation in randomized order. At the beginning of each visit, heart rate variability (HRV) is recorded for 5 minutes before stimulation to establish a resting baseline. Stimulation is applied for 20 minutes using the VaguStim device. Immediately after stimulation, HRV is recorded again for 5 additional minutes, followed by completion of a side-effect questionnaire documenting any sensations or adverse reactions. Following that, participants complete the STAI and PSS questionnaires to assess post-stimulation psychological state.Cognitive performance is then reassessed using the CogniFit digital battery.

This cross-over design enables within-subject comparison between active and sham stimulation and provides the structure needed to examine potential sex-related differences in autonomic, cognitive, and psychological responses to taVNS.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 30 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Healthy young adults aged 18-30 years
• Ability to provide informed consent
• Right-handed participants (to reduce variability in cognitive performance)
• Normal or corrected-to-normal vision and hearing
• Female participants tested during the follicular phase of the menstrual cycle (days 5-10) to minimize hormonal effects on cognition and vagal tone

Exclusion criteria

• History of neurological or psychiatric disorders
• Cardiovascular disease
• Use of psychoactive medications
• Substance dependence, including alcohol, illicit drugs, or nicotine
• Pregnancy or breastfeeding
• Skin conditions or ear anomalies that interfere with electrode placement
• Metal implants in the head or neck region
• History of epilepsy or migraine

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

---

60 participants in 2 patient groups

Active taVNS Stimulation

Experimental group

Description:

Active taVNS will be applied bilaterally to the cymba conchae and tragus regions using the VaguStim device. Stimulation will follow standard parameters used in cognitive studies to minimize cardiac side effects. Parameters: biphasic waveform, 25 Hz frequency, 250 μs pulse width, and intensity individually adjusted below the sensory threshold (0.5-4 mA). Each session will last 20 minutes.

Treatment:

Device: Active taVNS

Sham Stimulation

Sham Comparator group

Description:

For the sham condition, electrodes will be placed on the earlobe bilaterally, an area not innervated by the vagus nerve, using the same device and parameter settings but without delivering active stimulation. This setup controls for placebo effects.

Treatment:

Device: Sham Stimulation