tVNS and Approach-Avoidance Behavior in Anhedonia and Anxiety

NCT07476469 | Recruiting

• 2 other identifiers: BON0082024_EKEA.149
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates if anhedonia and anxiety symptoms are associated with alterations in reinforcement learning, effort trade-offs for wins vs. punishments, and foraging behavior under threat. Moreover, it will investigate whether these processes can be influenced by a metabolic load and/or transcutaneous vagus nerve stimulation (tVNS). The project consists of (a) an online reinforcement learning study, used to characterize learning, reward sensitivity, and meta-cognition, and (b) a laboratory study in which participants first undergo fMRI while completing an effort-based decision-making task. Second, participants will complete two sessions in VR with randomized active or sham tVNS during a foraging task before and after a caloric load with concurrent physiological recordings.

Conditions

Healthy Participants; Anxiety Disorders (With High Anxiety Symptoms); Depressive Disorders (With High Anhedonia Symptoms); Comorbid Depression and Anxiety Disorder (With High Anhedonia and High Anxiety Symptoms)

Keywords

Depression; Anhedonia; Anxiety; Vagusnerv-Stimulation; tVNS; Virtual Reality; fMRI

Outcome Measures

Primary Outcomes (4)

• Stimulation-induced changes in the number of rewards collected under threat (VR foraging task)

  The number of rewards collected during a VR foraging task will be compared between stimulation conditions (tVNS vs. sham).

  During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks)

• BOLD response during the effort-trade-off task (offer-phase)

  The outcome describes task-evoked neural activation (BOLD response) during the offer phase of the effort trade-off task. Neural activation is measured as a task-evoked BOLD response during offer presentation.

  Collected during fMRI session (single session throughout study completion ~35min per participant)

• Reward learning

  Reward learning is repeatedly measured during an online bandit task with fluctuating reward probabilities. Reward learning behavior will be collected online in 10 runs spread over 5 to 10 days, each including 150 trials.

  Online task performance assessed online before lab-visits (approximately 10 days)

• Metabolic state x stimulation-induced changes in the number of rewards collected under threat (VR task)

  The number of rewards collected during a VR foraging task will be compared between two different metabolic states (fasted vs. postprandial) and stimulation conditions (tVNS vs. sham).

  During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks)

Secondary Outcomes (31)

• BOLD response during the effort-trade-off task (feedback-phase)

  Collected during fMRI session (single session throughout study completion ~35min per participant)

• Choices in the effort trade-off task

  During a single fMRI session throughout study completion (approximately 3 weeks)

• Association between BOLD response during the effort-trade-off task (offer-phase) and effort discounting

  During a single fMRI session throughout study completion (approximately 3 weeks)

• Association between BOLD response during the effort-trade-off task (feedback phase) and effort-discounting

  During a single fMRI session throughout study completion (approximately 3 weeks)

• Effort-discounting

  During a single fMRI session throughout study completion (approximately 3 weeks)

Other Outcomes (11)

• SHAPS (Snaith-Hamilton Pleasure Scale)

  Assessed online before lab-visits (approximately 10 days)

• TEPS (Temporal Experience of Pleasure Scale)

  Assessed online before lab-visits (approximately 10 days)

• DARS (Dimensional Anhedonia Rating Scale)

  Assessed online before lab-visits (approximately 10 days)

Study Arms (4)

Healthy Controls

EXPERIMENTAL

The healthy control group will include participants without clinically relevant symptoms of anxiety or anhedonia. Inclusion criteria are a STICSA total score \<= 40 and a SHAPS total score below 23.5. Participants in this group must not meet the criteria for a current psychiatric diagnosis defined in the exclusion criteria, as confirmed by the Structured Clinical Interview for DSM (SCID).

Device: tVNS; Device: Sham

Anxiety

EXPERIMENTAL

The anxiety group will include participants with elevated anxiety symptoms, defined as a STICSA total score \>= 43. All participants must meet diagnostic criteria for a current anxiety disorder or/and current depressive disorder, confirmed by the SCID.

Device: tVNS; Device: Sham

Anhedonia

EXPERIMENTAL

The anhedonia group will include participants with elevated anhedonia symptoms, defined as a SHAPS total score greater than 29.5. All participants must meet diagnostic criteria for a current depressive disorder or/and current anxiety disorder, confirmed by the SCID.

Device: tVNS; Device: Sham

Comorbid anhedonia and anxiety

EXPERIMENTAL

The combined group will include participants with both elevated anxiety and anhedonia symptoms, defined as STICSA \>= 43 and SHAPS \> 29.5, respectively. All participants must meet diagnostic criteria for a current anxiety disorder or/and a current depressive disorder, confirmed by the SCID.

Device: tVNS; Device: Sham

Interventions

tVNS DEVICE

The intervention consists of event-triggered tVNS in the form of short pulses (\~1-5s; frequency: 25Hz). A non-CE-certified and non-medical device (tVNS® R tVNS technologies, for research purposes) will be used. Stimulation intensity will be individually calibrated to ensure perceptible (mild pricking) but non-painful stimulation for each participant. The protocol is the same for all groups.

Anhedonia; Anxiety; Comorbid anhedonia and anxiety; Healthy Controls

Sham DEVICE

The sham condition similarly consists of event-triggered, closed-loop stimulation, but without vagus nerve activation (short pulses of 1-5s; frequency: 25Hz). A non-CE-certified and non-medical device (tVNS® R, for research purposes) will be used. The manufacturer is not involved in the study. Stimulation intensity will be individually calibrated to ensure perceptible (mild pricking) but non-painful stimulation for each participant. The protocol is the same for all groups.

Anhedonia; Anxiety; Comorbid anhedonia and anxiety; Healthy Controls

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• BMI between 18,5 and 30,0 kg/m2,
• between 18 and 40 years of age, and
• be able and willing to provide informed consent.

You may not qualify if:

• have a high risk of suicide,
• have a lifetime diagnosis of severe neurological disorder (incl. ADHD), schizophrenia, bipolar disorder, or severe substance abuse, posttraumatic stress disorder, obsessive-compulsive disorder, diabetes, epilepsy, or coronary heart disease
• have fulfilled criteria for an eating disorder or somatic symptom disorder within the last 12-months,
• take medication (except psychopharmacological medication for MDD or anxiety), patients have to be on stable psychopharmacological medication for at least two months before study participation (minimizing confounding effects)
• contraindications for MRI (metal implants or claustrophobia)
• for female individuals if they are pregnant or nursing at the time,
• impaired movement ability or hearing
• impaired, uncorrected vision (need contact lenses)
• contraindications for tVNS hearing aids or diseased skin on the right ear.

Sponsors & Collaborators

• Dr. Nils B. Kroemer: lead
• University of Bonn: collaborator
• Else Kröner Fresenius Foundation: collaborator

Study Sites (1)

University Hospital Bonn, Bonn, Germany

Bonn, 53127, Germany

RECRUITING

Related Publications (1)

• Neuser MP, Teckentrup V, Kuhnel A, Hallschmid M, Walter M, Kroemer NB. Vagus nerve stimulation boosts the drive to work for rewards. Nat Commun. 2020 Jul 16;11(1):3555. doi: 10.1038/s41467-020-17344-9.

  PMID: 32678082 BACKGROUND

MeSH Terms

Conditions

Anxiety Disorders; Depressive Disorder; Depression; Anhedonia

Condition Hierarchy (Ancestors)

Mental Disorders; Mood Disorders; Behavioral Symptoms; Behavior; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Dr. Anne Kühnel

CONTACT

+49 228 28711519; akuehnel@uni-bonn.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. rer. nat.

Study Record Dates

• First Submitted: February 13, 2026
• First Posted: March 17, 2026
• Study Start: March 23, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Data will become available after an embargo period of 12 months after completion of the study.
• Access Criteria: Until the data is publicly available, researchers may contact the lead PI to gain access.

Locations

DE (1)