Stress, Healthy
Conditions
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.
Interventions
yohimbine 54mg + hydrocortisone 20mg oral
DEVICEmedial prefrontal cortex rTMS
1 Hz mPFC rTMS
DRUGPlacebo oral tablet
placebo stressor
DEVICEsham rTMS
sham mPFC rTMS
Sponsors
Wayne State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
sham (inactive) figure of 8 coil for rTMS, and placebo for pharmacological stressor
Intervention model description
Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| 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) |
| 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) |
Outcome results
None listed