HD-tDCS for Hallucinations

One in three patients with schizophrenia experiences hallucinations that are refractory to conventional pharmacotherapy. For refractory auditory hallucinations, transcranial direct current stimulation -tDCS- has been proposed as a novel therapeutic approach. Although promising beneficial effects on auditory hallucinations have been found by targeting the left frontal and temporoparietal cortex, the high variability observed in clinical response leaves much room for optimizing stimulation parameters. For instance, options should go beyond the left temporoparietal junction as a unique and single target of hallucinations, taking into account the personalization of the targeting based on the actual brain networks involved in hallucinations, including those beyond the auditory modality, as well as multimodal hallucinations.

The present study will take advantage of recent technological developments to propose a personalized therapeutic strategy to alleviate hallucinations in schizophrenia. This will involve:

* the simultaneous targeting of multiple brain regions with High-Definition (HD)-tDCS, which is known for its precise and longer-lasting effects compared to conventional tDCS.
* and the fMRI-capture of hallucinations, using a precise and reliable data-driven approach to identify the functional brain networks recruited during hallucinations.

The aim of the study is to assess whether repeated sessions of HD-tDCS guided using the fMRI capture of hallucinations can reduce multimodal hallucinations in patients with schizophrenia, compared to sham sessions of HD-tDCS.

The study is a multicentre, prospective, randomised, double-blind, parallel group, sham-controlled, two-arm clinical trial. Arm one is repeated active HD-tDCS guided using the fMRI-capture of hallucinations (20 sessions of stimulation over 10 days, 20 min/session). Arm two is the blinded sham repeated HD-tDCS guided by the fMRI-capture of hallucinations (20 sessions of sham stimulation over 10 days, 20 min/session).

Eligibility Criteria:
Inclusion Criteria:

* Females and males aged between 18 and 50
* Diagnosis of schizophrenia according to DSM 5.0 criteria
* Presence of dailyfrequent hallucinations (\> 2 / hour) despite the optimization of the antipsychotic dosage and molecule (based on the prescriber's judgment) for at least 6 weeks. The presence of such daily frequent refractory hallucinations will be operationalized by an interview with a trained psychiatrist.
* Patient under curatorship/guardianship or not
* Covered by a public health insurance
* Understanding French language
* Signed written informed consent after being informed about the study

Exclusion Criteria:

* Other disabling Axis Inpsychiatric conditions including a current diagnosis of a major depressive episode (uni- or bi- polar disorder) according to DSM 5, and substance use disorder (except tobacco)
* Use of hallucinogenic drugs
* Contraindications for magnetic resonance imaging or tDCS (neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes, cochlear implants, severe claustrophobia)
* Changes in the total PSAS and PANSS score of at least 15% between screening/inclusion (T0) and baseline visits (T1). This criterion will ensure the stability of symptoms before treatment.
* Pregnancy (controlled by urine pregnancy test in women of childbearing potential) or breastfeeding
* A clinical condition requiring inpatient procedure under constraint