tVNS and Approach-Avoidance Behavior in Anhedonia and Anxiety

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

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.

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.

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).

The outcome describes task-evoked neural activation (BOLD response) during the feedback phase of the effort trade-off task.

Neural activation is measured as a task-evoked BOLD response during feedback presentation.

Choices in the effort trade-off task will be assessed as a binary outcome of accept vs. reject.

The primary outcome is the association (regression coefficient) quantifying the relationship between effort discounting and neural activation (BOLD response) during the offer-phase of an effort trade-off task.

Neural activation is measured as a task-evoked BOLD response during offer presentation. Effort discounting is estimated from behavioral choices in the effort trade-off task using computational modeling.

The primary outcome is the association (regression coefficient) quantifying the relationship between effort-discounting and neural activation (BOLD response) during the feedback phase of an effort trade-off task.

Neural activation is measured as task-evoked BOLD response during feedback presentation.Effort-discounting is estimated from behavioral choices in the effort trade-off task using computational modeling.

The outcome describes effort-discounting derived from the effort trade-off task.

Effort-discounting is estimated from behavioral choices in the effort trade-off task using computational modeling.

The primary outcome is the association (regression coefficient) quantifying the relationship between individual differences in foraging during VR and task-evoked neural connectivity.

Task-evoked BOLD responses during the effort trade-off task is measured using functional magnetic resonance imaging (fMRI). Foraging in the VR task is the number of rewards collected.

The primary outcome is the association (regression coefficient) quantifying the relationship between individual differences in effort-discounting and task-evoked neural connectivity.

Task-evoked neural connectivity during the effort trade-off task is measured using functional magnetic resonance imaging (fMRI). Neural connectivity is quantified as region-of-interest-level functional connectivity. The number of rewards is measured in the VR foraging task.

The primary outcome is the comparison of time spent foraging (seconds) during the VR foraging task between stimulation conditions (tVNS vs. sham).

The primary outcome is the comparison of escape latency (seconds) during the VR foraging task between stimulation conditions (tVNS vs. sham).

The primary outcome is the comparison of heart rate increases following threat during the VR foraging task between active vs. sham tVNS.

Autonomic responses to threat are operationalized as the change in heart rate from a pre-threat baseline period (safety period preceding the trial) to the first minute following threat onset.

The primary outcome is the comparison of heart rate recovery following threat response during the VR foraging task between stimulation conditions (tVNS vs. sham).

The primary outcome is the comparison of habituation of heart rate response following threat over trials during the VR foraging task between active vs. sham tVNS.

The primary outcome is the comparison of the change in subjective metabolic state after receiving a caloric load between stimulation conditions (tVNS vs. sham).

Subjective metabolic state assessed during a VR foraging task using 0-100 Visual Analog Scales (VAS) of hunger and satiety. A metabolic state score is calculated as the difference between hunger and satiety ratings, scaled from -1 to 1 ((hunger-satiety)/100). The difference will then be compared between stimulation conditions.

The primary outcome is the comparison of affect between stimulation conditions (tVNS vs. sham).

Affective state is assessed using the Positive and Negative Affect Schedule (PANAS), administered as Visual Analog Scales (0-100). A composite affect score (positive - negative affect) is calculated from positive and negative affect ratings.

The primary outcome is the comparison of affect between metabolic state (fasted vs. postprandial) and stimulation condition (tVNS vs. sham). The primary analysis examines the interaction between metabolic state and stimulation condition.

Affective state is assessed using the Positive and Negative Affect Schedule (PANAS), administered as Visual Analog Scales (0-100). A composite affect score (positive - negative affect) is calculated from positive and negative affect ratings.

The primary outcome is the comparison of time spent foraging (seconds) during a VR foraging task between metabolic state (fasted vs. postprandial) and stimulation condition (tVNS vs. sham). The primary analysis examines the interaction between metabolic state and stimulation condition.

The primary outcome is the comparison of escape latency (seconds) during a VR foraging task between metabolic state (fasted vs. postprandial) and stimulation condition (tVNS vs. sham). The primary analysis examines the interaction between metabolic state and stimulation condition.

The outcome describes response times collected during the online task.

Response times (milliseconds) are collected in trials of the online reward learning task (10 runs with 150 each).

Choice accuracy (binary correct vs. incorrect) is derived from trials of the online reward learning task (10 runs with 150 each).

The outcome describes metacognitive calibration in a reward learning task.

Self-reported ratings are collected at the end of each run (10 runs) on a Visual Analog Scale (0-100 Visual Analog Scale) assessing subjective performance. Higher values represent better subjective performance. A metacognitive calibration score will be calculated as the difference between self-reported performance and objective task performance.

The outcome describes a mood state score calculated from data collected during the online reward learning task.

EMA questions (0-100 Visual Analog Scale) assessing mood state (happy and sad) will be asked before every run of the online task (10 runs). Mood state will be calculated as happy - sad.

The outcome describes the stress rating of participants collected during the online reward learning task.

EMA question (0-100 Visual Analog Scale) assessing subjective stress will be asked before every run of the online task (10 runs).

The primary outcome is the association (regression coefficient) quantifying the relationship between mood state and response times.

Response times (seconds) are derived from trials of the online reward learning task (10 runs with 150 trials each). EMA questions (0-100 Visual Analog Scale) assessing mood (happy - sad) are asked before every run of the online task (10 runs).

The primary outcome is the association (regression coefficient) quantifying the relationship between neural activity and behavioral tVNS response.

tVNS response is defined as the within-subject change in the number of rewards collected during VR foraging under active vs sham tVNS. Neural activation is measured as task-evoked BOLD response.

The primary outcome is the association (regression coefficient) quantifying the relationship between neural connectivity and behavioral tVNS response.

Behavioral response is defined as the within-subject change in the number of rewards collected during VR foraging under tVNS vs sham. Neural connectivity markers derived from fMRI-testing will be used to assess how neural connectivity explains interindividual variability in behavioral tVNS response.

The primary outcome is the association (regression coefficient) quantifying the relationship between cortisol and BOLD response during the effort-trade-off task.

Morning serum cortisol will be collected after an overnight fast at the laboratory visit immediately before the MRI session and quantified in nmol/L (expected range approx. 140-690nmol/L). Neural activation is measured as task-evoked BOLD response.

The primary outcome is the association (regression coefficient) quantifying the relationship between cortisol and behavioral tVNS response.

Morning serum cortisol will be collected after an overnight fast at the laboratory visit immediately before the MRI session and quantified in nmol/L (expected range approx. 140-690nmol/L). Behavioral response is defined as the within-subject change in number of rewards collected during VR foraging under active vs sham tVNS.

The primary outcome is the association (regression coefficient) quantifying the relationship between the value of insulin resistance and neural activation (BOLD responses) during an effort-trade-off-task.

Neural activation is measured as task-evoked BOLD response.

Insulin resistance is assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting plasma insulin and glucose concentrations obtained from morning blood samples.

The primary outcome is the association (regression coefficient) quantifying the relationship between insulin resistance and behavioral stimulation response during a VR foraging task.

Behavioral response to tVNS is measured as the change in the number of rewards collected under threat during a VR foraging task. Insulin resistance is assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting plasma insulin and glucose concentrations obtained from morning blood samples.

Body mass index will be included as a covariate in analyses involving metabolic, neural, and behavioral outcomes.

The primary outcome is the association (regression coefficient) quantifying the relationship between mood state and reward learning.

Reward learning is measured in the online reward learning task (10 runs with 150 trials each). EMA questions (0-100 Visual Analog Scale) assessing mood (happy - sad) are asked before every run of the online task (10 runs).

Self-report questionnaire assessing anhedonia severity. Used for grouping participants and associated with behavioral and neural outcomes.

Total scores range from 14 to 56 with higher scores reflecting higher anhedonia.

Questionnaire measuring anticipatory and consummatory pleasure. This outcome will be associated with behavioral and neural outcomes.

Total scores range from 18 to 108 with subscales scoring between 10-60 (anticipatory) and 8-48 (consummatory). Higher scores indicate greater hedonic capacity (lower anhedonia) while lower scores represent higher anhedonia symptoms.

Questionnaire assessing multiple facets of anhedonia. This outcome will be associated with behavioral and neural outcomes.

Total scores range from 0 to 68, with subscales scoring between 0-16 (hobbies, food, and social) and 0-20 (sensory). Higher scores indicate greater hedonic capacity (lower anhedonia) while lower scores represent higher anhedonia symptoms.

Self-report questionnaire assessing trait anxiety. This outcome will be associated with behavioral and neural outcomes.

Total scores range from 20 to 80 with higher scores indicating higher anxiety.

Questionnaire assessing depressive symptoms. Used as an additional symptom dimension. Total scores range from 0 to 63, with higher scores indicating greater depressive symptom severity.

Five questions (0-100 Visual Analog Scale) evaluating self-rated performance, self-rated performance compared to the days before, self-rated performance compared to others. Higher scores indicate better self-rated performance.

Ecological Momentary Assessments (EMA) using 0-100 Visual Analog Scale, administered repeatedly across online-task and lab sessions to capture current internal states (distraction, satisfaction, physical state, mental well-being, caloric intake, thirst, motivation).

Waist-to-hip ratio will be included as a covariate in analyses involving metabolic, neural, and behavioral outcomes.

Morning serum cortisol will be collected after an overnight fast at the laboratory visit immediately before the MRI session and quantified in nmol/L (expected range approx. 140-690nmol/L).

Cortisol will be included as a covariate in analyses involving metabolic, neural, and behavioral outcomes.

Insulin resistance is assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), calculated from fasting plasma insulin and glucose concentrations obtained from morning blood samples. A higher score indicates less insulin sensitivity.

HOMA-IR will be included as a covariate in analyses involving metabolic, neural, and behavioral outcomes.

Questionnaire measuring state and trait anxiety. Used for grouping participants and associated with behavioral and neural outcomes.

Total scores range from 21 to 84, with subscales scoring between 11-44 (somatic anxiety) and 10-40 (cognitive anxiety). Higher scores indicate higher anxiety.