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.
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.
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)
Crossover
tVNS
DeviceThe 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.
Sham
DeviceThe 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.
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).
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.
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.
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).
BOLD response during the effort-trade-off task (feedback-phase)
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
Choices in the effort trade-off task will be assessed as a binary outcome of accept vs. reject.
Association between BOLD response during the effort-trade-off task (offer-phase) and effort discounting
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.
Association between BOLD response during the effort-trade-off task (feedback phase) and effort-discounting
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.
SHAPS (Snaith-Hamilton Pleasure Scale)
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.
TEPS (Temporal Experience of Pleasure Scale)
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.
DARS (Dimensional Anhedonia Rating Scale)
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.
STAI (State-Trait Anxiety Inventory)
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.
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Dr. Nils B. Kroemer
Lead sponsor
University of Bonn
Sponsor institution
University of Bonn
Collaborator
Else Kröner Fresenius Foundation
Collaborator
