rTMS of Limbic Circuitry in Stress Modulation in Healthy Volunteers
- Conditions
- StressHealthy
- Interventions
- Drug: Placebo oral tabletDevice: medial prefrontal cortex rTMSDevice: sham rTMS
- Registration Number
- NCT04180969
- Lead Sponsor
- Wayne State University
- Brief Summary
This study will be conducted with healthy male and female participants. Aim 1 will determine during sham repetitive transcranial magnetic stimulation (rTMS) how a drug stressor combination (yohimbine + hydrocortisone) relative to placebo alters : (1a) impulsivity; (1b) mood; and (1c) physiology. Aim 2 will determine whether active rTMS over the medial prefrontal cortex alters the effects of stress-exposure on (2a) decision-making, (2b) mood, and (2c) biomarkers of stress.
- Detailed Description
This study will use a double-blind, within-subjects randomized crossover design. Each participant will complete 4 sessions in this two-factor (2x2) combinatorial design: 1Hz medial prefrontal cortex (mPFC) vs. sham repetitive transcranial magnetic stimulation (rTMS) X pharmacological stressor (yohimbine 54mg + hydrocortisone 20mg) vs. placebo, with each session separated by at least 1 week. Participants will be asked not to use alcohol or drugs for 24-hr before arriving at the lab. We expect to complete screen at least 20 individuals to complete 12 individuals in this study. Candidates will first undergo psychiatric and medical screening to rule out contraindications to participation. Once enrolled, each participant will complete, in randomized order, the 4 conditions above. Periodic measures will be collected before and after the rTMS/sham and stress/placebo interventions. These measures will include subjective, behavioral and physiological assessments, as well as saliva and blood samples.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Age 21-60 yr
- Right-handed
- Males and non-pregnant/non-lactating females
- Cognitively intact (total IQ score >80 on Shipley Institute of Living Scale)
- Screening cardiovascular indices must be within ranges that allow for safe use of stressor: resting HR 50-90 bpm, systolic BP 90-140 mmHg, and diastolic BP 50-90 mmHg
- Use alcohol and/or marijuana <3 times/week; each "time" should consist of <1 marijuana "joint" equivalent and <3 alcoholic drinks
- Under influence of any substance during session
- Past 7-day use of illicit drugs (excluding marijuana) based on Timeline Followback interview
- Urine positive for opioids, cocaine metabolites, benzodiazepines, barbiturates, amphetamines or pregnancy
- Medical conditions prohibiting use of rTMS (e.g. seizure history; using validated rTMS screening instrument)
- Lifetime diagnosis of: psychotic disorder, bipolar disorder, generalized anxiety disorder, obsessive compulsive disorder, or major depression that is not substance-induced
- Past-year substance use disorder
- Medical conditions making it unsafe for participation (e.g. neurological, cardiovascular, pulmonary, or systemic diseases)
- Lactose intolerance (placebo dose)
- Any prohibited medications: medications that lower seizure threshold, psychiatric medications, prescription pain medications, or blood pressure medications
- Chronic head or neck pain
- Taken part in any research studies in the past month
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description placebo stressor, sham rTMS Placebo oral tablet placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil placebo stressor, sham rTMS sham rTMS placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil placebo stressor, active rTMS medial prefrontal cortex rTMS placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex placebo stressor, active rTMS Placebo oral tablet placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex active stress, sham rTMS sham rTMS active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil active stress, sham rTMS yohimbine + hydrocortisone active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil active stress, active rTMS yohimbine + hydrocortisone active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex active stress, active rTMS medial prefrontal cortex rTMS active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex
- Primary Outcome Measures
Name Time Method Monetary Incentive Delay Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) number of rewards received, measure of motivation
Delay Discounting Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) rate of monetary discounting
Color-Word Stroop Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) reaction time (msec) measure of cognitive interference
Wisconsin Card Sorting Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) number of correct items, measure of ability to shift set and assesses cognitive flexibility
Digit Span Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) number of digits recalled, measure of verbal working memory
State-Trait Anxiety Inventory change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) questionnaire subscale that measures state anxiety
Effort Choice Task change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) number of progressive ratio (PR) choices vs. fixed ratio (FR) choices
Positive and Negative Affect Schedule (PANAS) positive affect change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) 10-item questionnaire sub scale that measures positive affect
Positive and Negative Affect Schedule (PANAS) negative affect change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) 10-item questionnaire sub scale that measures negative affect
Blood pressure change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Blood pressure (mm Hg)
Heart rate change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Heart rate (beats/min)
Plasma BDNF level change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Plasma brain derived neurotrophic factor level (pg/mL)
Saliva cortisol level change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Saliva cortisol level (µg/mL)
Saliva alpha-amylase level change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Saliva alpha-amylase level (U/mL)
Plasma prolactin level change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) Plasma prolactin level (pg/mL)
- Secondary Outcome Measures
Name Time Method