Externalization and Stimulation (STUPEFIX)

Modulation of Auditory Externalization Abilities by Transcranial Stimulation of the Brain Area Specifically Involved

The distinction between self-generated and external information is impaired in patients with schizophrenia, who are assumed to confuse imagination with real perceptions. To better understand the underlying mechanisms of these abnormalities, the investigator will investigate the brain mechanisms supporting auditory externalization. Auditory externalization is the ability to perceive whether a sound comes from inside or outside oneself. Our study, in healthy participants, will use functional brain imaging to identify the brain areas involved in the externalization of sound sources and to test whether neuromodulation of this area can modify this ability and provide a therapeutic lead in pathological populations

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Procedure: High-definition transcranial direct current (HD-tDCS), active condition; Procedure: High-definition transcranial direct current (HD-tDCS), placebo condition

Detailed Description

30 healthy participants will be included. The participants will undergo three separate visits. During the first one, the participants will listen to sounds coming from either internal or external sources while undergoing an fMRI session. This will allow us to identify the brain region involved in externalizing abilities with the highest activity. In the second and third visits, this specific region will be targeted by HD-tDCS (a non-invasive high-definition neuromodulation technique whose precision is enhanced by individual data) to modulate its activity and test its causal involvement in externalization processes. Each participant will receive both active and placebo stimulation, with the order counterbalanced. During the stimulation, participants will complete an externalization task, followed by a reality monitoring task and a self-agency task. Additionally, the investigator will gather socio-demographic and psychometric data.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marine MONDINO, PhD; Phone Number: +33 0437915565; Email: marine.mondino@ch-le-vinatier.fr
• Study Contact Backup: Name: Lydie SARTELET; Phone Number: +33 0437915531; Email: lydie.sartelet@ch-le-vinatier.fr

Study Locations

• France
  • Bron, France, 69678
    • Recruiting
    • Centre Hospitalier le Vinatier
    • Contact: Marine Mondino; Phone Number: +33 0437915565; Email: marine.mondino@ch-le-vinatier.fr
    • Contact: Jérôme Brunelin; Phone Number: +33 0437915297; Email: jerome.brunelin@ch-le-vinatier.fr
    • Sub-Investigator: Jerome Brunelin
    • Principal Investigator: Marine Mondino
    • Sub-Investigator: Frédéric Haesebaert

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Having given their written informed consent
• Affiliated with a social security scheme
• French speakers and readers

Exclusion Criteria:

• With contraindication to HD-tDCS stimulation or fMRI
• With a history of or current hearing problems, including tinnitus
• Taking medication (except contraceptives)
• With a history of or current psychiatric diagnosis (DSM-5 criteria)
• First-degree relatives with a diagnosis of schizophrenia spectrum disorder or bipolar disorder (DSM5)
• Have a personal history of neurological disorders or head trauma with loss of consciousness
• With an intellectual disability (Raven's Matrices)
• With developed musical abilities (i.e., regular practice of a musical instrument for at least 10 years with assiduity or at a music school or conservatory)
• Pregnant or nursing
• Being in a period of exclusion and/or having exceeded the annual indemnity ceiling (€4,500) for other clinical research.
• Under guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 15 healthy participants active then placebo; 15 healthy participants will receive a session of active HD-tDCS and then a session of placebo HD-tDCS.	Procedure: High-definition transcranial direct current (HD-tDCS), active condition; Participants will receive a session of active HD-tDCS at a current intensity of 2 mA for a duration of 25min. The placement of electrodes will be determined to specifically target the brain area that has been identified as being involved in the process of externalization, as evidenced by fMRI. During the stimulation, participants will be engaged in a computer-based externalization task.; Procedure: High-definition transcranial direct current (HD-tDCS), placebo condition; Participants will receive a session of placebo HD-tDCS, which will be delivered following the same procedures as active HD-tDCS but the intensity of the current will be set at 2mA during the 30 first seconds at the beginning of the 25-min period of the stimulation, and equal to 0 mA for the reminding period of stimulation to simulate the tingling sensation often experienced by individuals during active stimulation. The placement of electrodes will be determined to specifically target the brain area that has been identified as being involved in the process of externalization, as evidenced by fMRI. During the stimulation, participants will be engaged in a computer-based externalization task
Placebo Comparator: 15 healthy participants placebo then active; 15 healthy participants will receive a session of placebo HD-tDCS and then a session of active HD-tDCS.	Procedure: High-definition transcranial direct current (HD-tDCS), active condition; Participants will receive a session of active HD-tDCS at a current intensity of 2 mA for a duration of 25min. The placement of electrodes will be determined to specifically target the brain area that has been identified as being involved in the process of externalization, as evidenced by fMRI. During the stimulation, participants will be engaged in a computer-based externalization task.; Procedure: High-definition transcranial direct current (HD-tDCS), placebo condition; Participants will receive a session of placebo HD-tDCS, which will be delivered following the same procedures as active HD-tDCS but the intensity of the current will be set at 2mA during the 30 first seconds at the beginning of the 25-min period of the stimulation, and equal to 0 mA for the reminding period of stimulation to simulate the tingling sensation often experienced by individuals during active stimulation. The placement of electrodes will be determined to specifically target the brain area that has been identified as being involved in the process of externalization, as evidenced by fMRI. During the stimulation, participants will be engaged in a computer-based externalization task

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Externalization abilities	proportion of sounds perceived as coming from an external source in the externalization task (range 0-100%)	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reality monitoring performance	Scores obtained at the reality monitoring task (Brunelin et al., 2006) (accuracy, range = 0-100%)	one year
Self-agency	Percentage of voice deviation in the self-agency task (Subramaniam et al., 2018) (pitch perturbation and variability in peak deviation in cents, cents(t) = 1200 log2 (Hertz(t )/HertzRef), mean pitch perturbation response tracks = ±100 and ± 400)	one year
Psychometric characteristics that may influence externalization abilities and stimulation effects	Launay-Slade Hallucinations Scale scores between 0 and 64 (LSHS; Launay and Slade)	baseline
Psychometric characteristics that may influence externalization abilities and stimulation effects	Plymouth Sensory Imagery Questionnaire (PSIQ).Scores between 0 and 70.	baseline
Side effects of stimulation	Scores at the questionnaire on side effects of stimulation. Scores between 10 and 44 (higher scores mean worse outcome)	1 time before (baseline) and within 1 hour after stimulation
Mood	Mood self-questionnaire. Scores between 0 and 100 (higher scores mean worse outcome)	1 time before (baseline) and within 1 hour after stimulation

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier
• Investigators: Principal Investigator: Marine MONDINO, Phd, hospital le vinatier

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2024
• Primary Completion (Estimated): January 16, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: June 16, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: stimulation; auditory processing; reality-monitoring; externalization; HD-TDCS
• Other Study ID Numbers: 2023-A00452-43

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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