Investigating Stress-Induced Dopamine Release: a fMRI-PET Study

Overview

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: * 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.

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