Projet ANR-08-MNPS-0004 – CIMOCS : Inhibition corticale et contrôle moteur dans la schizophrénie
Programme : Maladies Neurologiques et Psychiatriques (MNP) 2008
Année de financement : 2008
Coordinateur du projet : INSERM - DR PARIS V (INSERM - DR PARIS V)
Partenaires : Centre Hospitalier Sainte Anne Paris; Centre Hospitalier Sainte Anne Paris; Centre Hospitalier Sainte Anne Paris; Institut national de la santé et de la recherche médicale
Montant : 446999.0 euros
Date de début : 2009
Durée : 36 mois
Résumé : Motor areas are of special interest in SZ as there is clear evidence of motor abnormalities independent of the effects of antipsychotic medication and that precede the onset of the disorder  These abnormalities have been proposed as a valid endophenotype in SZ. We propose. Our global objective is to study the cortical motor networks in SZ,
1) Behavioural motor performance of a set of motor ¿soft¿ signs, known to be altered in SZ, will be assessed and recorded by means of inertial sensors; 2) an fMRI-guided TMS study coupled to simultaneous EEG recording will reveal the reciprocal modulatory relations between the three main cortical regions involved in motricity 3) A selected set of candidate genes for SZ involved in cortical development and GABA. This part of the investigation takes into account that a) SZ is a disorder with an important genetic, neurodevelopmental dimension and b) evidences suggesting altered GABAergic transmission in this illness. 
 Converging lines of evidence supports the hypothesis that cerebral cortical function is subtly altered in this SZ. TMS studies in SZ have confirmed the existence of a defect in cortical inhibition Cellular and molecular studies suggest that altered GABA transmission could be at the origin of this dysfunction Motor areas are of special interest in SZ as there is clear evidence of motor abnormalities independent of the effects of antipsychotic medication and that precede the onset of the disorder  These sensorimotor abnormalities have been proposed as a valid endophenotype in SZ 
Our global objective is to study the cortical motor networks in SZ, from a 1) behavioural, 2) neurophysiological and 3) genetic point of view. To this end, three different groups will be studied: a group of schizophrenic patients, a group of non-affected siblings and a group of healthy control subjects. 
1) Behavioural motor performance of a set of motor ¿soft¿ signs, known to be altered in SZ, will be assessed and recorded by means of inertial sensors; 2) an fMRI-guided TMS study coupled to simultaneous EEG recording will reveal the reciprocal modulatory relations between the three main cortical regions involved in motricity, In addition, the TMS-EEG protocol will permit the first whole ¿head mapping of cortical excitability in SZ. 3) A selected set of candidate genes for SZ involved in cortical development and GABA transmission will be studied in the three groups. This part of the investigation takes into account that a) SZ is a disorder with an important genetic, neurodevelopmental dimension and b) evidences suggesting altered GABAergic transmission in this illness. 
This research will be the first comprehensive behavioural, neurophysiological and genetic study focused on motor function
 With guided magnetic stimulation of  4 specific motor and prefrontal areas and recording of EEG and CI indices in the motor cortex, we expect to substantiate the role of  each region in the regulation of cortical excitability, a marker which appears as consistently disturbed in schizophrenia. This could bring benefits on diagnostic and therapeutic levels. 
Whereas, the most studies do not differentiate clinical subgroups of schizophrenic patients, we expect greater disturbance of CI in disorganized patients, a subgroup with higher NSS scores, major cognitive impairment and worse prognosis. We plan to apply  the most accurate subtests of our paradigm  to the identification of adolescents at risk, particularly those in the so-called prepsychotic phase studied in our group We will look for the genetic background of GABA transmission possibly predicting response to therapeutic TMS