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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| placebo stressor, sham rTMS | Placebo Comparator | placebo stressor is lactose, and sham rTMS is inactive figure of 8 coil |
|
| placebo stressor, active rTMS | Experimental | placebo stressor is lactose, and active rTMS is 1Hz stimulation over the medial prefrontal cortex |
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| active stress, sham rTMS | Experimental | active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and sham rTMS is inactive figure of 8 coil |
|
| active stress, active rTMS | Experimental | active stressor is the combination of yohimbine 54mg + hydrocortisone 20mg, and active rTMS is 1Hz stimulation over the medial prefrontal cortex |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| yohimbine + hydrocortisone | Drug | yohimbine 54mg + hydrocortisone 20mg oral |
|
| Measure | Description | Time Frame |
|---|---|---|
| Color-Word Stroop Task | reaction time (msec) measure of cognitive interference | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Digit Span Task | number of digits recalled, measure of verbal working memory | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Wisconsin Card Sorting Task | number of correct items, measure of ability to shift set and assesses cognitive flexibility | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Monetary Incentive Delay Task | number of rewards received, measure of motivation | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Delay Discounting Task | rate of monetary discounting | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Effort Choice Task | number of progressive ratio (PR) choices vs. fixed ratio (FR) choices | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Positive and Negative Affect Schedule (PANAS) positive affect |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Mark K Greenwald, PhD | Wayne State University | Study Director |
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Full sharing plan is being developed.
Materials will only become available after the study is completed and the first manuscript from this project is published.
Qualified investigators may apply in writing to Dr. Greenwald
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| ID | Term |
|---|---|
| D015016 | Yohimbine |
| D006854 | Hydrocortisone |
| ID | Term |
|---|---|
| D046948 | Secologanin Tryptamine Alkaloids |
| D026121 | Indole Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
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Double-blind, 1Hz mPFC (vs. sham) rTMS X stressor (vs. placebo), 4-session, within-subjects, randomized crossover design
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sham (inactive) figure of 8 coil for rTMS, and placebo for pharmacological stressor
| medial prefrontal cortex rTMS | Device | 1 Hz mPFC rTMS |
|
| Placebo oral tablet | Drug | placebo stressor |
|
| sham rTMS | Device | sham mPFC rTMS |
|
10-item questionnaire sub scale that measures positive affect
| change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Positive and Negative Affect Schedule (PANAS) negative affect | 10-item questionnaire sub scale that measures negative affect | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| State-Trait Anxiety Inventory | questionnaire subscale that measures state anxiety | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Blood pressure | Blood pressure (mm Hg) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Heart rate | Heart rate (beats/min) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Saliva cortisol level | Saliva cortisol level (µg/mL) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Saliva alpha-amylase level | Saliva alpha-amylase level (U/mL) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Plasma prolactin level | Plasma prolactin level (pg/mL) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| Plasma BDNF level | Plasma brain derived neurotrophic factor level (pg/mL) | change from pre- to post-intervention in each of the 4 sessions (through study completion, about 1 month total) |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D054836 | Indolizidines |
| D007212 | Indolizines |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D015062 | 11-Hydroxycorticosteroids |
| D006889 | Hydroxycorticosteroids |
| D000305 | Adrenal Cortex Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D015065 | 17-Hydroxycorticosteroids |