Use of tDCS Applied to the Orbitofrontal Cortex to Improve Risky Decision-making in a Clinical Population (tDCSDeMOStim)

Use of tDCS (Transcranial Direct Current Stimulation) Applied to the Orbitofrontal Cortex to Improve Risky Decision-making in a Clinical Population: a Proof-of-concept Study

Decision-making is a complex cognitive function that has been the subject of extensive scientific research in the fields of cognitive and computational neuroscience. It relies on a cerebral network that encompasses cortico-subcortical pathways. The orbitofrontal cortex (OFC) plays a significant role in decision-making by assigning values to guide choices. Risky decision-making is observed in several psychiatric pathologies, including depression and bipolar disorder, and it may constitute an endophenotype of suicide. In the project presented here, we propose to use transcranial direct current stimulation (tDCS) to target decision-making in patients suffering from mood disorders.

Study Overview

• Status: Recruiting
• Conditions: Depression; Mood Disorders; Suicide
• Intervention / Treatment: Device: Active transcranial direct current stimulation (tDCS); Device: Sham transcranial direct current stimulation (tDCS)

Detailed Description

The primary objective is to assess the ability of tDCS applied to the orbitofrontal cortex to improve decision-making, as measured by the Iowa Gambling Task, compared to a placebo stimulation in patients suffering from mood disorders.

The secondary objectives are as follows:

• To assess whether the evolution of decision-making under tDCS stimulation is independent of emotional changes (sadness, anxiety).
• To evaluate if tDCS stimulation of the orbitofrontal cortex improves motor inhibition, assessed using the D2-test, compared to a placebo stimulation.
• To determine if tDCS stimulation of the orbitofrontal cortex reduces sensitivity to interference, assessed with the Stroop test, compared to a placebo stimulation.
• To evaluate if tDCS stimulation of the orbitofrontal cortex enhances cognitive inhibition, measured by the Go-no go test, compared to a placebo stimulation.

This is a prospective monocentric interventional randomised controlled trial with two parallel groups, one receiving active treatment with tDCS and the other receiving a placebo (sham tDCS). The randomization will be performed in variable-sized blocks and will be stratified based on the current mood state (current depression versus current euthymia). It is a single-blind study where the patients and the outcome assessor are blinded to the type of treatment received.

Recruitment will take place at "la Clinique des Maladies Mentales et de l'Encéphale de l'Hôpital Sainte-Anne" and will involve hospitalized patients as well as those in outpatient care. Pre-inclusion visit involve patient selection, verification of inclusion criteria, and the provision of information documents. Inclusion visit occur at least one day later, lasting for three hours. It involves the verification of both inclusion and exclusion criteria, obtaining informed consent, randomization, collecting socio-medical-demographic data, and conducting psychometric and neuropsychological assessments. Stimulation visit, also scheduled at least one day later and lasting three hours, encompass the measurement of primary and secondary evaluation criteria immediately before and after tDCS stimulation. A group guessing test concludes the study.

An interim analysis is planned, and an Independent Data Monitoring Committee (IDMC) will be established to oversee the data.

• Study Type: Interventional
• Enrollment (Estimated): 124
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michel DANON, MD; Phone Number: +33625201929; Email: m.danon@ghu-paris.fr
• Study Contact Backup: Name: Fabrice JOLLANT, MD PhD; Email: jollantf@gmail.com

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • GHU Paris Psychiatrie et Neurosciences - Hôpital Sainte-Anne - CMME
    • Contact: Michel DANON, MD; Phone Number: +33625201929; Email: m.danon@ghu-paris.fr
    • Contact: Philip GORWOOD, MD PhD; Email: p.gorwood@ghu-paris.fr
    • Principal Investigator: Michel DANON, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients under consideration should either be receiving outpatient or inpatient care.
• Patients must be between the ages of 18 and 65, inclusive.
• According to DSM-5 criteria, patients should be diagnosed with either unipolar or bipolar depressive disorder. This includes individuals currently experiencing a characterized depressive episode with mild to moderate intensity, those in partial remission, or those in full remission.
• Patients must have provided informed consent.
• Patients should be enrolled in a social security plan.

Exclusion Criteria:

• Patient unwilling to participate in the research.
• Non-French-speaking individuals.
• Individuals deprived of liberty by judicial or administrative decision, such as those under guardianship or curatorship or involuntarily hospitalized.
• Pregnant or breastfeeding women.
• Current hypomanic or manic episode as per DSM-5 criteria due to motor agitation issues.
• Ongoing electroconvulsive therapy (ECT) treatment or within the last 6 months.
• Patients with active implantable medical devices.
• Epilepsy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tDCS active comparator; Active transcranial Direct Current Stimulation (tDCS): Stimulation of 1.5 mA for 30 minutes.	Device: Active transcranial direct current stimulation (tDCS); Description of the tDCS session: Placement of conductive electrodes, attached to the scalp. The electrodes are placed in individual sponge cases moistened with a saline solution. A sponge towel is placed on the patient's shoulders to prevent any clothing from becoming damp. The electrodes are held in place by a dedicated net.; The anode is placed in the left supraorbital region (site Fp1 EEG 10/20 system). The cathode was placed in the right supraorbital region (site Fp2 EEG 10/20 system).; Patients received 1.5 mA stimulation for 30 minutes.
Sham Comparator: tDCS sham comparator; Sham transcranial Direct Current Stimulation (tDCS): Effective stimulation of 1.5 mA for 30 seconds, then the current is switched off. The complete session lasts 30 minutes, with 29 minutes and 30 seconds without stimulation.	Device: Sham transcranial direct current stimulation (tDCS); Description of the tDCS session: Placement of conductive electrodes, attached to the scalp. The electrodes are placed in individual sponge cases moistened with a saline solution. A sponge towel is placed on the patient's shoulders to prevent any clothing from becoming damp. The electrodes are held in place by a dedicated net.; The anode is placed in the left supraorbital region (site Fp1 EEG 10/20 system). The cathode was placed in the right supraorbital region (site Fp2 EEG 10/20 system).; Patients received effective stimulation of 1.5 mA for 30 seconds, after which the current was switched off. The entire session lasted 30 minutes, with 29 minutes and 30 seconds without stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The study aims to assess the effectiveness of tDCS applied to the orbitofrontal cortex in enhancing decision-making abilities, as measured by the Iowa Gambling Task, when compared to placebo stimulation in patients with mood disorders.	The primary outcome measure is the net score on the Iowa Gambling Task over 100 selections. This score represents the difference between the number of selections from low-risk and long-term advantageous decks and the number of selections from high-risk and long-term disadvantageous decks during 100 selections. This score ranges from -100 to 100, and the lower the score, the riskier the decision-making. This measurement will be taken immediately before and after tDCS stimulation.	Day 1 (end of study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess whether tDCS stimulation of the OFC improves reduces susceptibility to interference compared to placebo stimulation.	Emotional stroop task : Difference in reaction time. The higher the score, the greater the susceptibility to interference. This measurement will be taken immediately before and after tDCS stimulation.	Day 1 (end of study)
To assess whether tDCS stimulation of the OFC improves cognitive inhibition compared to placebo stimulation.	Go-no go task : Commission error rate. The lower the score, the more effective cognitive inhibition is. This measurement will be taken immediately before and after tDCS stimulation.	Day 1 (end of study)
To assess whether the change in decision-making under tDCS stimulation is independent of emotional changes (sadness).	PANAS : Positive and Negative Affect Schedule. Positive Affect Score range from 10 - 50, with higher scores representing higher levels of positive affect Negative Affect Score range from 10 - 50, with lower scores representing lower levels of negative affect.	Day 1 (end of study)
To assess whether the change in decision-making under tDCS stimulation is independent (STAI:State-Trait Anxiety Inventory)	STAI score range from 20 to 80. STAI scores are commonly classified as "no or low anxiety" (20-37), "moderate anxiety" (38-44), and "high anxiety" (45-80). These measurements will be taken immediately before and after tDCS stimulation.	Day 1 (end of study)
To assess whether tDCS stimulation of the OFC improves motor inhibition compared to placebo stimulation (Sustained-Attention test: d2-test)	d2-test: the test taker is required to scan the lines and cross out all occurrences of the letter 'd' with two dashes while ignoring all other characters. During the test, the subject must delete as many 'd2' as possible in 20 seconds per line (there are 14 lines on the sheet). This measurement will be taken immediately before and after tDCS stimulation.	Day 1 (end of study)

Collaborators and Investigators

• Sponsor: Centre Hospitalier St Anne
• Investigators: Principal Investigator: Michel DANON, MD, GHU Paris Pyschiatrie & Neurosciences

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2021
• Primary Completion (Estimated): May 15, 2024
• Study Completion (Estimated): May 15, 2024

Study Registration Dates

• First Submitted: October 19, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 31, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Transcranial Direct Current Stimulation; Cognition; Endophenotype
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Self-Injurious Behavior; Suicide; Mood Disorders
• Other Study ID Numbers: D20-P041

Drug and device information, study documents

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