tVNS and Approach-Avoidance Behavior in Anhedonia and Anxiety

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.

The overarching goal of this project is to investigate the potential of modulating internal signals in patients with mood and anxiety disorders to improve the balance between approach and avoidance behavior. To this end, tVNS (vs. sham) will be used to alter foraging behavior under threat. To address the inherent heterogeneity of symptoms, it is planned to recruit participants with anxiety symptoms (ANX), anhedonia symptoms (ANH), both anxiety and mood symptoms (ANX+ANH), and healthy control participants (HCP). The groups will be matched for the group-average and distribution of age, sex, and BMI (age: 18 to 40 years, BMI 18.5 - 30 kg/m²). After an online assessment, diagnostic visit, and MRl-based phenotyping, internal signals are targeted with tVNS and a caloric load to shift the approach-avoidance behavior. In a randomized crossover study, participants will receive stimulation (tVNS or sham) in a hungry state (\>4 h after the last meal at a time when they would typically have their next meal) and complete a VR-based foraging task under threat. They will then receive a standardized caloric load (milkshake containing \~400 kcal) and repeat the task with the same stimulation in a different metabolic state (postprandial). Crucially, participants can move freely during the task so that behavioral adaptations in response to threats (e.g., escaping a panther) as well as physiological adaptations (e.g., heart rate) and their recovery can be measured. The study is split into three parts: 1. Online screening and behavioral characterization At least 250 participants (≥150 with clinically relevant symptoms; STICSA \>= 43 and/or SHAPS \> 29.5) will complete baseline questionnaires (anhedonia (SHAPS, TEPS, and DARS), anxiety (STICSA and STAI), depression (BDI), substance abuse) and an approx. two weeks online reinforcement learning task (10 runs). Behavioral indices (choices, response times) and computational modeling parameters (e.g., learning rates, reward sensitivity, decision noise) will be derived. At the end of each run, participants provide metacognitive performance ratings, enabling assessment of deviations between subjective and objective performance. 2. Neural correlates of approach-avoidance (phenotyping) A subset of participants (high anxiety, high anhedonia, combined, and healthy controls (STICSA \<= 40 and SHAPS \< 23.5); \~26 per group) will undergo laboratory-based testing. Assessments include diagnostic interviews, fasting blood samples (glucose, insulin, triglycerides, cortisol), and fMRI during an effort trade-off task comparing the effort to gain rewards and to avoid punishments. 3. tVNS intervention The same participants will then complete a randomized, sham-controlled crossover trial. Participants will perform a VR foraging task under threat in two metabolic states: hungry (\>4 h fasted) and postprandial (following a standardized caloric load \~400kcal). During both states, participants will receive either active or sham tVNS. Behav trial.show_full_description

Inclusion Criteria: * 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. Exclusion Criteria: * 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.