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

NCT ID: NCT07256080

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2026-05-31

Brief Summary

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.

Detailed 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Active taVNS Stimulation

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.

Group Type: EXPERIMENTAL

Active taVNS

Intervention Type: DEVICE

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

This intervention corresponds to the Active taVNS Stimulation arm.

Sham Stimulation

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.

Group Type: SHAM_COMPARATOR

Sham Stimulation

Intervention Type: DEVICE

Sham stimulation will be delivered using the same VaguStim device, but electrodes will be placed bilaterally on the earlobe, an area not innervated by the vagus nerve. Device parameters will be set to match the active condition, but no true vagus nerve stimulation is delivered. This procedure controls for placebo and participant expectancy effects.

This intervention corresponds to the Sham Stimulation arm.

Interventions

Active taVNS

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

This intervention corresponds to the Active taVNS Stimulation arm.

Intervention Type: DEVICE

Sham Stimulation

Sham stimulation will be delivered using the same VaguStim device, but electrodes will be placed bilaterally on the earlobe, an area not innervated by the vagus nerve. Device parameters will be set to match the active condition, but no true vagus nerve stimulation is delivered. This procedure controls for placebo and participant expectancy effects.

This intervention corresponds to the Sham Stimulation arm.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Bahçeşehir University

OTHER

Sponsor Role: lead

Responsible Party

Yara Atef Skout

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ali Veysel Ozden

Role: STUDY_CHAIR

Bahçeşehir University

Central Contacts

Yara A Skout

Role: CONTACT

yaraskout@gmail.com

+905316766782

Ali Vesel Ozden Assistant Professor

Role: CONTACT

aliveysel.ozden@bau.edu.tr

00905065994233

Other Identifiers

61351342/020-93

Identifier Type: -

Identifier Source: org_study_id