Keeping Mind and Body in Sync: Non-invasive Vagus Nerve Stimulation as a Tool to Modulate Stomach-Brain Coupling in Depression
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 入组人数
- 80
- 试验地点
- 2
- 主要终点
- Stimulation-induced mid-term changes in gastric motility
研究概览
简要总结
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.
详细描述
It is planned to conduct a randomized cross-over study including two neuroimaging sessions to assess the effect of acute tVNS (vs. sham) on stomach-brain coupling using concurrent fMRI and EGG. Furthermore, to evaluate potential medium-term effects of repeated applications of tVNS (vs. sham), changes across two weeks in gastric myoelectric frequency and interoception/somatic sensations as well as metabolic and mood states will be evaluated using a combination of lab-based with ecological momentary assessments (EMA).
Consequently, three major hypotheses will be tested:
Hypothesis 1: Participants suffering from MDD show altered stomach-brain coupling compared to matched healthy control participants; inter-individual differences in interoceptive measures/somatic sensations correlate with stomach-brain coupling.
Hypothesis 2: tVNS enhances stomach-brain coupling in a vagal afferent network.
Hypothesis 3: In participants suffering from MDD, tVNS influences interoception/somatic sensations and normalizes gastric myoelectric frequency over an extended stimulation period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Stimulation-induced mid-term changes in gastric motility
时间窗: 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
时间窗: 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 acute neural changes in food cue reactivity
时间窗: 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 changes in stomach-brain coupling
时间窗: 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
时间窗: 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 somatic symptoms
时间窗: 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
时间窗: 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 behavioral changes in invigoration
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Stimulation-induced mid-term changes in blood parameters(Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period))
- Stimulation-induced mid-term changes in motivation(Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period))
- Stimulation-induced mid-term changes in physical activity(During extended stimulation period (up to approx. 2 weeks))
- Stimulation-induced mid-term changes in heart rate(During extended stimulation period (up to approx. 2 weeks))
- Stimulation-induced mid-term changes in positive and negative affect(During extended stimulation period (up to approx. 2 weeks))
- Stimulation-induced mid-term changes in self-reported interoception(Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period))
- Stimulation-induced acute changes in blood parameters(Before and after stimulation/MRI scan (up to three hours))
- Stimulation-induced mid-term changes in composition of microbiome(Pre- and post comparison after approx. 2 weeks (beginning and end of extended stimulation period))
研究者
Dr. Nils B. Kroemer
Prof. Dr. rer. nat.
University of Bonn