Stress Response
Conditions
Brief summary
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.
Detailed description
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: * Neurochemical level: dopamine transmission measured with positron emission tomography * Functional brain connectivity: resting-state networks measured with functional magnetic resonance imaging * Hormonal level: adrenocorticotropic hormone and cortisol levels measured with blood samples * Cognitive level: decision-making and memory assessed with delay-discounting task and reality-monitoring task, respectively * Molecular level: expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples Exploratory measure: Brain-Derived Neurotrophic Factor and cytoplasmic catechol-O-methyltransferase polymorphisms of participants involved in differential Transcranial direct current stimulation response will be assessed.
Interventions
DEVICEtDCS actif
Active brain stimulation
DEVICEtDCS Sham
Sham brain stimulation
Sponsors
Hôpital le Vinatier
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
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.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* \- Men and women aged between 18- and 30-year-old * Non-smoker * Non-psychotropic user
Exclusion criteria
* \- Have a psychiatric or somatic disorder * Have a first-degree family history of a psychiatric disorder * Pregnant or nursing women * Be on medication, with the exception of oral contraceptives * Contraindications to tDCS or MRI examination * Participants with pacemaker or cardiac or cerebral implant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dopamine transmission measured with positron emission tomography | One year | Subcortical dopaminergic transmission will be analyzed, using \[11C\]raclopride PET activity (D2 receptor antagonist) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hormonal stress reactivity | One year | ACTH level will be measured |
| Cognitive stress reactivity | One year | 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. |
| Functional brain connectivity | One year | Resting-state functional connectivity |
| Assessment of brain-derived neurotrophic factor before and after transcranial direct current stimulation. | One year | Exploratory measure: brain-derived neurotrophic factor polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess. |
| Assessment of Cytoplasmic catechol-O-methyltransferase polymorphisms before and after transcranial direct current stimulation. | One year | Exploratory measure: Cytoplasmic catechol-O-methyltransferase polymorphisms of participants, involved in differential Transcranial direct current stimulation response, will be assess. |
| Expression of genes involved in the glucocorticoid receptor signaling pathway measured through blood samples | One year | Expression rates of genes involved in the glucocorticoid receptor signaling pathway |
Countries
France
Outcome results
None listed