Reference Measurements of the Neuronal Integration Window and Anatomical and Functional MRI (Magnetic Resonance Imaging)

Reference Measurements of the Neuronal Integration Window and Anatomical and Functional MRI

Our studies on MRI (Magnetic resonance imaging) biomarkers in neuropsychiatric disorders rely on reference data from control subjects which are dependent from our scanner. Due to the upcoming replacement of our MR scanner, the investigators need to 'recalibrate' our current database by acquiring the same data on both the old and the new device from a small group of controls (n = 36 to 40). This will be combined with measures of cortical excitability using robotized TMS (transcranial magnetic stimulation) that will be combined to MRI biomarkers in forthcoming studies.

Therefore, the primary objective of this biomedical trial is to collect MRI and physiological measurements in normal subjects whose characteristics match to our study populations.

An inclusion period of 4 months will allow for the inclusion of the necessary subjects.

Controls will be recruited through mailings, classified ads and/or posters, adapting age, gender and education criteria as the investigators go along to match investigators's target populations.

Making contact and appointments: During the telephone contact with the subject, the investigators provide the initial information concerning the objectives, the course and the constraints of the study. An appointment will be made after checking that the main eligibility criteria have been met.

Information and selection visit (min. 24 hours before V0): This visit can be carried out by web-conference or on one of the technical platforms (iCube laboratory).

After checking that the participant meets all the eligibility criteria, the investigator will repeat the information about the protocol and its constraints and answer the subject's questions. The patient will be offered a reflection period of at least 24 hours. If the patient accepts, an appointment will be made for the inclusion visit.

Inclusion visit (V0) - MRI -1: This visit will take place on the "3Tesla MRI" technical platform. After answering any further questions, the investigator will obtain the patient's free, informed and written consent.

The investigator then connects to Hédonix®, a dedicated web application with a personal login and password. He then fills in the entry form: surname, first name, date of birth, e-mail, telephone number, address. Hédonix® automatically generates an entry identification number and a password for the subject.

The investigator uploads the scanned version of the signed consent forms to Hedonix® and collects the following information Socio-demographic data: gender, age, level of education, age of learning French, level of language proficiency, professional activity, marital status, lifestyle, parents' socio-economic level. Vascular risk factors: habitus (cigarettes, alcohol, coffee etc.), blood pressure, weight, water and fat content (impedance measurement), height, waist circumference, capillary blood sugar.

Personal medical history (including psychiatric, neurological, substance abuse, immune disorders), incidents during pregnancy (weight loss, infection), treatment, stress, term, season, delivery complication). Family history with a family tree up to the 3de degree of relatedness if possible (cousins/great grandparents), collecting as much information as possible about possible psychiatric, neurological and systemic diseases Hetero-questionnaires and cognitive tests: Psychometrics (fNART= french National Adult Reading Test). Attentional testing (TAP = Tests of Attentional Performance, continuous performance test , semantic priming ) Self-questionnaires: The subject logs in to Hedonix® with his/her login and password to complete the following self- questionnaires.

'Characterisation and screening: MRI and TMS* contraindication checklist (double-check - possible study exit if screened at this stage), Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) level 1 screening instrument (D1-DS= screening for the main psychiatric diseases), manual dominance (EHI= Edinburgh Handedness Inventory), sedation (ESS= Epworth Sleepiness Scale), screening for a bipolarity (MDQ= Mood Disorder Questionnaire), ruminations (mini-CERTS= Mini Cambridge-Exeter Repetitive Thought Scale), psychometrics (Mill-Hill, EQ= Empathy Quotient), personality traits (BFI= Big Five Inventory, TIPI=Temperament assessment, chronotype), stress exposure (past Acquired Brain Injury (ABI) or recent Life Stressor Condition (LSC)).

Current symptoms (assessed over the previous month): apathy (AES-S=Apathy Evaluation Scale ), tiredness (MFI =Multidimensional Fatigue Inventory ), physical activity (RGQ= Ricci and Gagnon Questionnaire), depression (IDS30-SR= Inventory of Depressive Symptomatology (subject rated)), anhedonia (SHAPS= Snaith-Hamilton Pleasure Scale, TEPS= Temporal Experience of Pleasure Scale).

For normative purposes: ECJM (Moral Choice and Judgment Evaluation) IRM-1 : On the same day, the MRI-1 will be performed on the 3T Vério Siemens MRI of the iCube laboratory's iBiSA-labelled (Infrastructures in Biology, Health, and Agronomy (a French national label for high-level scientific platforms) IRIS platform (Research Infrastructure for Imaging and Health, a French platform for advanced biomedical imaging).

Visit V1 (week1 to week 8) - MRI - 2: MRI 2 will be performed on the 3T Vério Siemens MRI of the IRIS platform of the iCube laboratory.

Visit V2 (w2 to w12) - Mapping and excitability of motor cortex: Physiological measurements will be carried out at CEMNIS (Centre de neuro-Modulation Non-Invasive de Strasbourg), a "robotic rTMS" (repetitive Transcranial Magnetic Stimulation) platform.

The subject will begin by performing psychophysical tests measuring the window of perception of simultaneity in visual, auditory and bimodal modalities.

Then the mapping and measurement of excitability, inhibition and "temporal integration window" parameters will be performed using our robotic TMS device under neuro-navigation.

Visit V3 (w20 to w28) - MRI-1: This visit will take place on the "3T MRI" technical platform of the IRIS platform (iCube laboratory). The subject logs in to Hedonix® with his/her login and password to fill in the following self- questionnaires concerning current symptoms (assessed over the previous month): apathy (AES-S), tiredness (MFI), physical activity (RGQ), depression (IDS30-SR), anhedonia (SHAPS, TEPS).

The MRI-1 will be performed on the new 3T Vida Siemens MRI of the IRIS platform of the iCube laboratory. The sequences will have the same purpose and use the same parameters as the MRI-1. The functional novelty will be the ability to record EEG (electroencephalogram) activity at the same time, which will allow the effects of changes in alertness to be assessed, something that could not be coupled with pre-therapy MRI on our previous MRI without a change of antenna

Visit V4 (w21 to w32) - MRI-2: This visit should be at least one week later than the previous one. MRI-2 (n°4) will be performed on the new 3T Vida Siemens MRI and the dedicated EEG of the IRIS platform of the iCube laboratory. The sequences will have the same purpose and will use the same parameters as the MRI-2. Most of the sequences are functional, but the acceleration of acquisition times will not result in a significant reduction of the total examination time as the latter will be used to increase the number of volumes acquired.

Inclusion Criteria:

• Men or women aged 18 to 86 inclusive;
• Affiliated to a social health insurance scheme
• Able to understand the objectives and risks of the research and to give dated and signed informed consent;
• B2 or above level of French language according to the European Framework of Reference for Languages;
• No personal or family psychiatric history of endogenous psychosis, including substance abuse (excluding moderate tobacco, alcohol and caffeine use);
• No chronic pathology requiring treatment (mainly diabetes, hypertension, hyperlipidemia or cholesterolemia);
• Matched on age, gender and education level of the patients included in our different studies
• Woman of childbearing age: negative urine pregnancy test at the inclusion visit and effective contraception throughout the study (intrauterine device, sterilisation, oestrogen or progestin per os, injectable or as an implant or ring).

Exclusion Criteria:

• Contraindication to MRI or rTMS: presence of a non-removable ferromagnetic foreign body, prosthesis, pacemaker, medication delivered by an implanted pump, vascular clip or stent, heart valve or ventricular bypass, epilepsy;
• History that may affect brain anatomy or be related to an abnormality (neurosurgery, epilepsy, stroke, head injury with loss of consciousness for more than 15 minutes and mental retardation - Intelligence Quotient (IQ) < 70 on the fNART);
• History of potentially affecting brain function (general anaesthesia or Electroconvulsive Therapy (ECT) < 3 months prior to inclusion);
• Breastfeeding women ;
• Pregnant women ;
• Serious or unstabilised somatic pathology ;
• Chronic intake of a treatment related to an ongoing disease;
• Deprived of liberty, in forced care or under legal protection ;
• Under guardianship or curatorship ;
• Emergency or life-threatening situation) ;
• Exclusion period (determined by a previous or current study).