Vagus Nerve Stimulation and Approach-Avoidance Behavior in Anhedonia and Anxiety
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Stimulation-induced changes in the number of rewards collected under threat (VR foraging task)
研究概览
简要总结
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.
详细描述
The overarching goal of this project is to investigate the potential of modulating internal signals in patients with mood and anxiety disorders to improve the balance between approach and avoidance behavior. To this end, tVNS (vs. sham) will be used to alter foraging behavior under threat.
To address the inherent heterogeneity of symptoms, it is planned to recruit participants with anxiety symptoms (ANX), anhedonia symptoms (ANH), both anxiety and mood symptoms (ANX+ANH), and healthy control participants (HCP). The groups will be matched for the group-average and distribution of age, sex, and BMI (age: 18 to 40 years, BMI 18.5 - 30 kg/m²). After an online assessment, diagnostic visit, and MRl-based phenotyping, internal signals are targeted with tVNS and a caloric load to shift the approach-avoidance behavior. In a randomized crossover study, participants will receive stimulation (tVNS or sham) in a hungry state (>4 h after the last meal at a time when they would typically have their next meal) and complete a VR-based foraging task under threat. They will then receive a standardized caloric load (milkshake containing ~400 kcal) and repeat the task with the same stimulation in a different metabolic state (postprandial). Crucially, participants can move freely during the task so that behavioral adaptations in response to threats (e.g., escaping a panther) as well as physiological adaptations (e.g., heart rate) and their recovery can be measured.
The study is split into three parts:
- Online screening and behavioral characterization At least 250 participants (≥150 with clinically relevant symptoms; STICSA > 43 and/or SHAPS > 29.5) will complete baseline questionnaires (anhedonia (SHAPS, TEPS, and DARS), anxiety (STICSA and STAI), depression (BDI), substance abuse) and an approx. two weeks online reinforcement learning task (10 runs). Behavioral indices (choices, response times) and computational modeling parameters (e.g., learning rates, reward sensitivity, decision noise) will be derived. At the end of each run, participants provide metacognitive performance ratings, enabling assessment of deviations between subjective and objective performance.
- Neural correlates of approach-avoidance (phenotyping) A subset of participants (high anxiety, high anhedonia, combined, and healthy controls (STICSA < 40 and/or SHAPS < 23.5); ~26 per group) will undergo laboratory-based testing. Assessments include diagnostic interviews, fasting blood samples (glucose, insulin, triglycerides, cortisol), and fMRI during an effort trade-off task comparing the effort to gain rewards and to avoid punishments.
- tVNS intervention The same participants will then complete a randomized, sham-controlled crossover trial. Participants will perform a VR foraging task under threat in two metabolic states: hungry (>4 h fasted) and postprandial (following a standardized caloric load ~400kcal). During both states, participants will receive either active or sham tVNS. Behavioral outcomes will be combined with physiological measures (e.g., heart rate) to assess the effects of vagal stimulation on approach-avoidance trade-offs.
Hypotheses:
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 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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)
- •contraindications for MRI (metal implants or claustrophobia)
- •for female individuals if they are pregnant or nursing at the time,
- •impaired movement ability or hearing
- •impaired, uncorrected vision (need contact lenses)
- •contraindications for tVNS hearing aids or diseased skin on the right ear.
研究组 & 干预措施
Healthy Controls
The healthy control group will include participants without clinically relevant symptoms of anxiety or anhedonia. Inclusion criteria are a STICSA total score below 40 and a SHAPS total score below 23.5. Participants in this group must not meet the criteria for a current psychiatric diagnosis defined in the exclusion criteria, as confirmed by the Structured Clinical Interview for DSM (SCID).
干预措施: tVNS (Device)
Healthy Controls
The healthy control group will include participants without clinically relevant symptoms of anxiety or anhedonia. Inclusion criteria are a STICSA total score below 40 and a SHAPS total score below 23.5. Participants in this group must not meet the criteria for a current psychiatric diagnosis defined in the exclusion criteria, as confirmed by the Structured Clinical Interview for DSM (SCID).
干预措施: Sham (Device)
Anxiety
The anxiety group will include participants with elevated anxiety symptoms, defined as a STICSA total score greater than 43. All participants must meet diagnostic criteria for a current anxiety disorder or/and current depressive disorder, confirmed by the SCID.
干预措施: tVNS (Device)
Anxiety
The anxiety group will include participants with elevated anxiety symptoms, defined as a STICSA total score greater than 43. All participants must meet diagnostic criteria for a current anxiety disorder or/and current depressive disorder, confirmed by the SCID.
干预措施: Sham (Device)
Anhedonia
The anhedonia group will include participants with elevated anhedonia symptoms, defined as a SHAPS total score greater than 29.5. All participants must meet diagnostic criteria for a current depressive disorder or/and current anxiety disorder, confirmed by the SCID.
干预措施: Sham (Device)
Anhedonia
The anhedonia group will include participants with elevated anhedonia symptoms, defined as a SHAPS total score greater than 29.5. All participants must meet diagnostic criteria for a current depressive disorder or/and current anxiety disorder, confirmed by the SCID.
干预措施: tVNS (Device)
Comorbid anhedonia and anxiety
The combined group will include participants with both elevated anxiety and anhedonia symptoms, defined as STICSA > 43 and SHAPS > 29.5, respectively. All participants must meet diagnostic criteria for a current anxiety disorder or/and a current depressive disorder, confirmed by the SCID.
干预措施: tVNS (Device)
Comorbid anhedonia and anxiety
The combined group will include participants with both elevated anxiety and anhedonia symptoms, defined as STICSA > 43 and SHAPS > 29.5, respectively. All participants must meet diagnostic criteria for a current anxiety disorder or/and a current depressive disorder, confirmed by the SCID.
干预措施: Sham (Device)
结局指标
主要结局
Stimulation-induced changes in the number of rewards collected under threat (VR foraging task)
时间窗: During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks)
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)
时间窗: Collected during fMRI session (single session throughout study completion ~35min per participant)
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
时间窗: Online task performance assessed online before lab-visits (approximately 10 days)
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)
时间窗: During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks)
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).
次要结局
- Choice accuracy in the online task(Assessed online before lab-visits (approximately 10 days))
- BOLD response during the effort-trade-off task (feedback-phase)(Collected during fMRI session (single session throughout study completion ~35min per participant))
- Choices in the effort trade-off task(During a single fMRI session throughout study completion (approximately 3 weeks))
- Association between BOLD response during the effort-trade-off task (offer-phase) and effort discounting(During a single fMRI session throughout study completion (approximately 3 weeks))
- Association between BOLD response during the effort-trade-off task (feedback phase) and effort-discounting(During a single fMRI session throughout study completion (approximately 3 weeks))
- Effort-discounting(During a single fMRI session throughout study completion (approximately 3 weeks))
- Association between BOLD responses during effort trade-offs and number of rewards during VR(Neural data: During a single fMRI session throughout study completion (approximately 3 weeks); Behavioral data: During sham stimulation session throughout study completion (approximately 3 weeks))
- Association between neural connectivity and number of rewards during VR(Neural data: During a single fMRI session throughout study completion (approximately 3 weeks); Behavioral data: During sham stimulation sessions throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in time spent foraging under threat (VR foraging task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in escape latency under threat (VR foraging task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in threat-evoked heart rate increase (VR foraging task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in heart rate recovery following threat (VR foraging task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in habituation of heart rate responses following threat (VR foraging task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in subjective metabolic state (VR foraging task)(During each stimulation session (tVNS vs. sham) throughout study completion (approximately 3 weeks))
- Stimulation-induced changes in affect (PANAS)(During each stimulation session (tVNS vs. sham) throughout study completion (approximately 3 weeks))
- Metabolic state x stimulation-induced changes in affect (PANAS)(During each stimulation session (tVNS vs. sham) throughout study completion (approximately 3 weeks))
- Metabolic state x stimulation-induced changes in time spent foraging under threat (VR task)(During each stimulation session (active and sham) throughout study completion (approximately 3 weeks))
- Metabolic state x stimulation-induced changes in escape latency under threat (VR task)(During each stimulation session (tVNS and sham) throughout study completion (approximately 3 weeks))
- Response times in the online task(Assessed online before lab-visits (approximately 10 days))
- Metacognitive calibration (performance-rating coupling)(Assessed online before lab-visits (approximately 10 days))
- Ecological Momentary Assessments (EMA) for mood(Assessed online before lab-visits (approximately 10 days))
- Ecological Momentary Assessments (EMA) for stress(Assessed online before lab-visits (approximately 10 days); EMA data: Collected before every online session (x 10))
- Association between Ecological Momentary Assessments (EMA) and response times in the online task(Assessed online before lab-visits (approximately 10 days))
- Association between BOLD response during the effort-trade-off task and tVNS-induced changes in the number of rewards collected(Neural markers: Collected during fMRI session (single session, ~30 min per participant); Behavioral data: Collected during VR sessions with two visits per participant (throughout study completion, approx. 3 weeks))
- Association between neural connectivity and tVNS-induced changes in number of rewards collected(Neural markers: Collected during fMRI session (single session, ~30 min per participant); Behavioral data: Collected during VR sessions with two visits per participant (throughout study completion, approx. 3 weeks))
- Associations between baseline cortisol and neural activation(Blood draw: Collected before the MRI session; Neural activation: During a single MRI session throughout study completion (approx. 3 weeks))
- Association between baseline cortisol and tVNS-induced changes in the number of rewards collected(Blood draw: Collected before the MRI session, Behavioral data: Collected during VR sessions with two visits per participant (throughout study completion, approx. 3 weeks))
- Association between insulin resistance and BOLD response during the effort-trade-off task(Blood samples and neural activation assessed during a single MRI session throughout study completion (approximately 3 weeks))
- Association between insulin resistance and tVNS-induced changes in number of rewards collected(Behavioral outcomes and biomarker measures assessed throughout study completion (approximately 3 weeks))
- BMI (Body-Mass-Index)(Collected throughout study completion (approximately 3 weeks))
- Association between Ecological Momentary Assessments (EMA) and reward learning in the online task(Assessed online before lab-visits (approximately 10 days))
研究者
Dr. Nils B. Kroemer
Prof. Dr. rer. nat.
University of Bonn