tVNS Effects on Motivation in Depression

Study Overview
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Brief Summary
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Attaining goals or rewards commonly entails response costs. In light of cost and benefits, how do participants decide what effort should be put in to give it a shot? Figuratively, you may go with your gut, but the literal contribution of the gut-brain axis in allocating effort is poorly understood to date. Here, the investigators propose to investigate non-invasive transcutaneous vagal nerve stimulation (tVNS) as a potential modulator of energy metabolism and response vigor. Since the neural mechanisms causing the diverse cognitive and behavioral effects of the stimulation remain largely elusive, the investigators will use computational modeling of instrumental behavior and determine the primary metabolic effects of the stimulation. The investigators hypothesize that tVNS will lead to activation of afferent targets in the brain. In turn, the elicited brain activation is expected to mediate the cognitive effects of the stimulation. This may affect both sides of the utility equation because anti-depressive effects may correspond to boosting the benefit of effort whereas anti-nociceptive effects may reduce perceived costs of effort. Collectively, dissecting the cognitive effects of non-invasive tVNS in healthy individuals may facilitate the more widespread use as a treatment in mental disorders that are characterized by metabolic alterations such as depression.

Official Title
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The Effects of Transcutaneous Vagus Nerve Stimulation on Motivation in Major Depressive Disorder

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Device: transcutaneous vagus nerve stimulation
* Device: sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 30 kg/m^2 > BMI > 18.5 kg/m^2 Exclusion Criteria: lifetime brain injury coronary heart disease and occurred apoplexy schizophrenia bipolar disorder implants (e.g., cochlea implant) asthma 12 month severe substance use disorders (DSM-V), except tobacco obessive compulsive disorder somatic symptom disorder eating disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-depressed control participants: sham first, active taVNS second<br>Non-depressed control participants receive sham stimulation in the first session (biphasic stimulation with a frequenyc of 25 Hz, 30s OFF/30s ON at the earlobe (sham) for 1.5 h). In a second identical session, they receive active stimulation with the same parameters (at the cymba conchae). | Device: transcutaneous vagus nerve stimulation<br>* Non-invasive brain stimulation technique that is used to stimulate vagal afferent projections to the nucleus of the solitary tract. Invasive VNS has been approved for the treatment of treatment-resistant depression.<br>* Other names: transcutaneous auricular vagus nerve stimulation;Device: sham stimulation<br>* Sham procedure for active transcutaneous vagus nerve stimulation<br>* Other names: transcutaneous stimulation of the earlobe;|
| Experimental: Patients with major depressive disorders: sham first, active taVNS second<br>participants with depression receive sham stimulation in the first session (biphasic stimulation with a frequenyc of 25 Hz, 30s OFF/30s ON at the earlobe (sham) for 1.5 h). In a second identical session, they receive active stimulation with the same parameters (at the cymba conchae). | Device: transcutaneous vagus nerve stimulation<br>* Non-invasive brain stimulation technique that is used to stimulate vagal afferent projections to the nucleus of the solitary tract. Invasive VNS has been approved for the treatment of treatment-resistant depression.<br>* Other names: transcutaneous auricular vagus nerve stimulation;Device: sham stimulation<br>* Sham procedure for active transcutaneous vagus nerve stimulation<br>* Other names: transcutaneous stimulation of the earlobe;|
| Experimental: Patients with major depressive disorders: active taVNS first, sham second<br>participants with depression receive active stimulation in the first session (biphasic stimulation with a frequenyc of 25 Hz, 30s OFF/30s ON at the cymba conchae (active) for 1.5 h). In a second identical session, they receive sham stimulation with the same parameters (at the earlobe). | Device: transcutaneous vagus nerve stimulation<br>* Non-invasive brain stimulation technique that is used to stimulate vagal afferent projections to the nucleus of the solitary tract. Invasive VNS has been approved for the treatment of treatment-resistant depression.<br>* Other names: transcutaneous auricular vagus nerve stimulation;Device: sham stimulation<br>* Sham procedure for active transcutaneous vagus nerve stimulation<br>* Other names: transcutaneous stimulation of the earlobe;|
| Experimental: Non-depressed control participants: active taVNS first, sham second<br>Non-depressed control participants receive active stimulation in the first session (biphasic stimulation with a frequenyc of 25 Hz, 30s OFF/30s ON at the cymba conchae (active) for 1.5 h). In a second identical session, they receive sham stimulation with the same parameters (at the earlobe). | Device: transcutaneous vagus nerve stimulation<br>* Non-invasive brain stimulation technique that is used to stimulate vagal afferent projections to the nucleus of the solitary tract. Invasive VNS has been approved for the treatment of treatment-resistant depression.<br>* Other names: transcutaneous auricular vagus nerve stimulation;Device: sham stimulation<br>* Sham procedure for active transcutaneous vagus nerve stimulation<br>* Other names: transcutaneous stimulation of the earlobe;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Food reward ratings | Operationalized via visual analogue scale ratings of liking [-100 - 100] and wanting [0-100] in a food cue reactivity task | during stimulation (compared to sham) | 
| Motivation to work for rewards: frequency of button presses to gain food an monetary rewards | Operationalized via the relative frequency of button presses on an Xbox controller in an effort allocation task during either the first seconds of each trial (invigoration) or each complete trial (maintenance) | during stimulation (compared to sham) | 
| Reward learning: correct choices | Operationalized via number of correct value-based choices in a valenced go/no-go learning task | during stimulation (compared to sham) | 
| Positive and negative mood | Operationalized via visual analogue ratings (0-100) of positive and negative affect schedule mood items | Pre stimulation and 20 minutes post stimulation (compared to sham) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anhedonia, vigor, vagus nerve stimulation, food reward, reward learning, mood