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The stress response is mediated by the activation of the hypothalamo-pituitary-adrenal axis and the sympathetic nervous system, leading to glucocorticoid and catecholamines release respectively. This stress response is regulated by feedback loops, involving cortical and subcortical structures.
Non-invasive brain stimulation applied over the dorsolateral prefrontal cortex modulates the subcortical dopaminergic transmission at rest and can reduce the hormonal and cognitive alterations induced by stress. This study aims to investigate the Non-invasive brain stimulation -induced modulation of dopamine transmission in an acute stress situation.
Objective: to investigate the influence of Dorsolateral Prefrontal Cortex stimulation during acute stress on the subcortical dopamine transmission in healthy subjects.
Method: 30 healthy subjects will be enrolled and randomized into 2 parallel groups. 15 participants will receive active Transcranial direct current stimulation , the other 15 participants will receive sham Transcranial direct current stimulation.
Transcranial direct current stimulation procedure: active Transcranial direct current stimulation corresponds to 30min of stimulation at 1mA intensity . The sham stimulation corresponds to 30s of real stimulation.
Stress paradigm: In order to induce moderate stress in humans in laboratory condition, the investigators will use the Maastricht Acute Stress test . This test is a combination between physical, hand immersion in cold water and cognitive calculation stress. The test will start 5 minutes after the beginning of stimulation session.
Stress measures: the stress response will be evaluated at the following levels:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active tDCS | Active Comparator | Active brain stimulation Direct current stimulation of DLPFC for 30min with an intensity of 1mA |
|
| Sham tDCS | Sham Comparator | Sham brain stimulation Direct current stimulation of DLPFC for 30sec with an intensity of 1mA |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tDCS actif | Device | Active brain stimulation |
| |
| tDCS Sham |
| Measure | Description | Time Frame |
|---|---|---|
| Dopamine transmission measured with positron emission tomography | Subcortical dopaminergic transmission will be analyzed, using [11C]raclopride PET activity (D2 receptor antagonist) | One year |
| Measure | Description | Time Frame |
|---|---|---|
| Functional brain connectivity | Resting-state functional connectivity | One year |
| Hormonal stress reactivity | ACTH level will be measured |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jérôme BRUNELIN, PhD | Vinatier Hospital PsyR2 Team | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ch Le Vinatier | Lyon | Auvergne-Rhône-Alpes | 69678 | France |
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| ID | Term |
|---|---|
| D015775 | Fractures, Stress |
| ID | Term |
|---|---|
| D050723 | Fractures, Bone |
| D014947 | Wounds and Injuries |
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In a randomized controlled double-blind study, 30 healthy subjects, will be randomly assigned to 2 groups. A group of 15 participants will receive 30 minutes of active tDCS (1mA, 30 minutes with the anode at the left DLPFC and the cathode at the right DLPFC); a group of 15 participants will receive 30 minutes of placebo stimulation. All participant will be in a PET-MRI scanner for 110min, during which they will undergo the stimulation (either active or sham). During this stimulation session, all participants will undergo a standardized stress test combining psychosocial stress and physical stress.
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The subject will be blind of the treatment he receives (active or placebo). The experimenter, caregiver and investigator will also be blinded from stimulation (active or placebo).
Each subject will be assigned a randomization code, corresponding to the code to enter the tDCS device. This system allows the person who administers tDCS and the subject receiving the stimulation to be blind.
| Device |
Sham brain stimulation |
|
| One year |
| Cognitive stress reactivity | Decision-making capacities will be measured using a computerized version of the DDT in which participants have to choose between 2 rewards. Memory capacities will be measured using a computerized task evaluating reality-memory. | One year |
| Expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples | Expression rates of genes involved in the glucocorticoid receptor signaling pathway | One year |
| Assessment of brain-derived neurotrophic factor before and after transcranial direct current stimulation. | Exploratory measure: brain-derived neurotrophic factor polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess. | One year |
| Hormonal stress reactivity | Cortisol level will be measured | One year |
| Assessment of Cytoplasmic catechol-O-methyltransferase polymorphisms before and after transcranial direct current stimulation. | Exploratory measure: Cytoplasmic catechol-O-methyltransferase polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess. | One year |