Investigating Stress-Induced Dopamine Release: a fMRI-PET Study (ISIDORE)

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.

Study Overview

• Status: Completed
• Conditions: Stress Response
• Intervention / Treatment: Device: tDCS actif; Device: tDCS Sham

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Rhone Alpes
    • Lyon, Rhone Alpes, France, 69678
      • CH Le Vinatier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active tDCS; Active brain stimulation Direct current stimulation of DLPFC for 30min with an intensity of 1mA	Device: tDCS actif; Active brain stimulation
Sham Comparator: Sham tDCS; Sham brain stimulation Direct current stimulation of DLPFC for 30sec with an intensity of 1mA	Device: tDCS Sham; Sham brain stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional brain connectivity	Resting-state functional connectivity	One year
Hormonal stress reactivity	ACTH level will be measured	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

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Investigators: Study Director: Jérôme BRUNELIN, PhD, Vinatier Hospital PsyR2 Team

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Actual): October 24, 2024
• Study Completion (Actual): October 24, 2024

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 4, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2022-A00907-36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No