Transcutaneous non-invasive vagus nerve stimulation (tVNS): Participants receive tVNS during the neuroimaging sessions and the extended stimulation period. To stimulate vagal afferents, the electrode will be placed at the cymba conchae of the right ear using a previously established, conventional stimulation protocol (25 Hz, 30s on/30s off cycle; NEMOS device, Cerbomed, Erlangen, Germany). To improve blinding, the stimulations intensities will be adjusted to correspond to a mild pricking sensation for tVNS and sham.
The extended stimulation period in the experimental group involves six sessions with at least 1.5h of stimulation (stimulation in the lab or at home with home device using the same stimulation protocol as during the neuroimaging sessions; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany).
Sham stimulation: The control intervention consists of a sham stimulation. In the neuroimaging session the electrode will be placed upside down to stimulate the earlobe, which is not innervated by vagal afferent fibers. To improve blinding, the same stimulation protocol as for the tVNS will be applied (25 Hz, 30s on/30s off cycle; NEMOS device, Cerbomed, Erlangen, Germany) and stimulation intensities will be adjusted to correspond to a mild pricking sensation.
During the extended stimulation period, the electrode will be placed at the cymba conchae, but only receive a low-intensity stimulation below the perception threshold (0.1mA). To ensure blinding, participants will be instructed that the extended stimulation period will examine the effects of a low- vs. high-intensity tVNS protocol. Each repeated stimulation period will involve six sessions with at least 1.5h of low-intensity stimulation (stimulation in the lab or at home with home device; tVNS R device, tVNS Technologies GmbH, Erlangen, Germany).
Study summary
The overarching goal of the project is to determine whether differences in stomach-brain coupling contribute to key symptoms of major depressive disorder (MDD) and whether transcutaneous non-invasive vagus nerve stimulation (tVNS) may serve as a non-invasive intervention to improve aberrant interoceptive signaling in participants suffering from MDD.
Eligibility
Sex
ALL
Min age
18 Years
Max age
55 Years
Healthy volunteers
Accepted
Inclusion Criteria:
* Between 18 and 55 years of age
* BMI between 18.5 and 30kg/m\^2
* Legally valid declaration of consent
* MDD group: current major depressive episode based on DSM V criteria
Exclusion Criteria:
* Current or past diagnosis of brain injury, epilepsy, schizophrenia, bipolar disorder, severe substance use disorder (exception: tobacco), coronary heart disease, stroke
* Following diagnosis within 12 months before start of experiment: obsessive compulsive disorder, somatic symptom disorder, eating disorder
* Contraindications for MRI (e.g. metal implants, claustrophobia) or tVNS (e.g. piercings, sore or diseased skin areas on the outer right ear)
* Pregnant and breastfeeding women are not included
* Unclear ability to give consent
Primary outcome measure(s)
Stimulation-induced acute changes in stomach-brain coupling — During MRI scan (up to 120 minutes) Stomach-brain coupling will be assessed using phase-locking values (PLV) at baseline and during tVNS/sham stimulation concurrent to electrogastrogram (EGG) measurements in the MRI. PLV will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham) with a focus on core regions of the gastric network (postcentral gyrus, cingulate gyrus, precuneus, occipital cortex, fusiform gyrus, inferior frontal gyrus, inferior and superior parietal lobe, thalamus, and inferior cerebellum) and the vagal afferent pathway (nucleus of the solitary tract (NTS), ventral tegmental area (VTA), substantia nigra, hypothalamus, amygdala, putamen, caudate, nucleus accumbens, hippocampus, insula, ventromedial prefrontal cortex, lateral orbitofrontal cortex, dorsal anterior cingulate cortex). PLV will be correlated with self-reported interoception, somatic symptoms, and depressive symptoms (see below).
Stimulation-induced acute changes in gastric motility — During MRI scan (up to 120 minutes) The gastric myoelectric frequency will be assessed during the MRI sessions at baseline and during tVNS and sham stimulation using an EGG. Acute changes in gastric peak frequency will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced mid-term changes in gastric motility — Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period) The gastric myoelectric frequency will be assessed at the beginning and end of the extended stimulation periods using an EGG. Data will be collected at baseline and during tVNS and sham stimulation and mid-term changes in gastric peak frequency from the beginning to the end of the extended stimulation periods will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced mid-term changes in self-reported interoception — Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period) Interoception is assessed by using the Multidimensional Assessment of Interoceptive Awareness questionnaire, version 2 (MAIA-2). Changes in awareness of bodily sensations will be assessed from the beginning to the end of the extended stimulation period and compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced mid-term changes in somatic symptoms — Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period) The Patient Health Questionnaire-15 (PHQ-15) will be used as self-report measurements to assess changes in severity of somatic symptoms from the beginning to the end of the extended stimulation periods. Changes across time will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced mid-term changes in depressive symptoms — Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period) The Beck's Depression Inventory (BDI-II) will be used to assess changes in depressive symptoms from the beginning to the end of the extended stimulation periods. Changes across time will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced acute neural changes in food cue reactivity — During MRI scan of a food bidding task (~13 minutes) Brain activity (BOLD signal) in response to food stimuli (contrasted with office supplies) and during exerting effort on a grip force device will be analyzed by focusing on brain regions associated with the vagal afferent pathway. Brain activity will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced acute behavioral changes in invigoration — During MRI scan of a food bidding task (~13 minutes) Invigoration related to food stimuli (contrasted with office supplies) will be operationalized via the relative effort exerted on a grip force device. Invigoration will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced acute neural changes during foraging — During MRI scan of a foraging task (~25 minutes) Brain activity (BOLD signal) during a foraging task will be analyzed by focusing on brain regions associated with the vagal afferent pathway. Brain activity will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham).
Stimulation-induced acute behavioral changes in foraging decisions — During MRI scan of a foraging task (~25 minutes) Decisions to accept or reject an offered option during a foraging task will be compared between groups (HC, MDD) and stimulation conditions (tVNS, sham). Analyses will focus on acceptance rates during different environments (poor and rich environment) for options differing in the effort needed to accept the option and the earned outcome and learning parameters based on trial-to-trial choices.
Trial sites (1)
Facility
City
Region
Status
Section of Medical Psychology, Department of Psychiatry & Psychotherapy, Faculty of Medicine, University of Bonn
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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