Section: Partnerships and Cooperations

National Initiatives

ANR

ANR HM-TC

Participants : Olivier Colliot [Correspondant] , Marie Chupin, Didier Dormont, Denis Schwartz, Dominique Hasboun, Linda Marrakchi-Kacem, Claire Cury.

• Project acronym: HM-TC

• Project title: Model of the hippocampo-cortical connectivity in “temporal consciousness” in normal and pathological memory derived from multimodal anatomical and functional brain imaging (aMRI, DT-MRI, MEG, fMRI)

• Duration: Nov 2009- Nov 2014

• Amount: 2M€

• Coordinator: Olivier Colliot (ARAMIS) and Gianfranco Dalla Barba

• Other partners: CENIR, ENS Cachan, Neurospin, Grenoble Institut des Neurosciences

• Abstract: The aim of this project is to evaluate the role of the medial temporal lobe and its connections with various cortical regions in temporal consciousness related tasks and to derive a neuro-computational model of memory processing from multimodal imaging data. Temporal consciousness is defined as the ability to specify one’s own time-location with respect to past, present and future, and is thus a more general framework than episodic memory. Based on an original cognitive model and relying on memory dysfunctions called confabulations, different groups of participants (controls, patients with Alzheimer’s disease, patients with several memory disorders) will be evaluated through cognitive tests, MEG, anatomical, functional and diffusion-tensor MRI. New signal and image processing methods will be developed for all these modalities, in order to describe in a more robust and precise way both the anatomy and the function of the medial temporal lobe. First, using in vivo ultra high field MRI acquisitions (7 Tesla), we will build a precise anatomical atlas of the hippocampus and its inner structure. This model will allow designing efficient MEG source reconstruction in these regions, and new methods to analyse anatomical and functional connectivity. Using the most recent mathematical achievements in the theory of diffeomorphic deformations, we will propose new registration and morphometry methods in order to analyze very precisely the structural alterations of the medial temporal lobe. These new methods will be applied to the neuroimaging data acquired for the project in order to analyse extensively the relationships between memory disorders and structural and functional brain alterations revealed by neuroimaging.

ANR PREV-DEMALS

Participants : Olivier Colliot [Correspondant] , Marie Chupin, Stanley Durrleman, Anne Bertrand.

• Project acronym: PREV-DEMALS

• Project title: Predict to prevent frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS)

• Duration: Avr 2015 - Avr 2019

• Amount: 487k€

• Coordinator: Isabelle Le Ber

• Other partners: ICM, AP-HP, CHR de Lille, CHU Limoges, CHU Rouen, Laboratory of Biomedical Imaging

• Abstract: The project focuses on C9ORF72, the most frequent genetic form of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Since 2006, major discoveries have helped elucidate the pathological bases and linked FTLD and ALS: 1) TDP-43 aggregates in neurons and 2) C9ORF72 mutations in both disorders. Two major pathological subtypes are now defined in FTLD, FTLD-TDP and FTLD-TAU. C9ORF72 mutations (associated to FTLD-TDP) are the most frequent genetic causes of FTLD (15%), FTLD-ALS (65%) and ALS (40%). No curative treatment actually exists, but therapeutics emerged against tau aggregation. The objectives of the project are to develop appropriate cognitive, brain imaging markers and peripheral biomarkers of the early phase of FTLD, to follow disease progression and to guide future targeted therapeutic trials. To address this questions, we will conduct a multimodal study (cognition, brain structural MRI, brain metabolism - FDG-PET) in C9ORF72 families. The cohort will be followed at 3-time points (M0, M18, M36). Longitudinal analyses will aim at characterizing the trajectory of decline across time. Brain structural changes will be evaluated by 1) morphometric analysis to assess global brain atrophy, cortical thickness and study of the cortical sulci; 2) functional connectivity analysis of resting-state MR data; 3) structural connectivity analysis of diffusion-weighted MRI. Brain metabolism will be evaluated with FDG-PET. We will use the most recent RNA sequencing technology to detect gene expression and RNA splicing alterations in lymphocytes of patients and presymptomatic carriers. The discovery of new markers involved in FTLD will have practical consequences for early and accurate diagnosis of FLD and ALS disease.

IHU

General program

Participants : Olivier Colliot, Mario Chavez, Stanley Durrleman, Marie Chupin, Didier Dormont, Dominique Hasboun, Damien Galanaud, Fabrizio de Vico Fallani.

• Project acronym: IHU-A-ICM

• Project title: Institute of Translational Neuroscience

• Founded in 2011

• General Director: Bertrand Fontaine

• The IHU-A-ICM program was selected, in 2011, in a highly competitive national call for projects. A 10-year, 55M€ program, has been implemented by a recently created foundation for scientific cooperation. Based on the clinical and scientific strenghts of the ICM and the hospital Department of Nervous System Diseases, it mainly supports neuroscience research, but is also invested in improving care and teaching. ARAMIS is strongly involved in the IHU-A-ICM project, in particular in WP6 (neuroimaging and electrophysiology), WP7 (biostatistics), WP2 (Alzheimer) and WP5 (epilepsy). We have started collaborations with the new bioinformatics/biostatistics platform (IHU WP7, head: Ivan Moszer), in particular through a joint project on the integration of imaging and genomics data.

Internal Research projects

Participants : Mario Chavez, Fabrizio de Vico Fallani.

• Project title: Non-invasive manipulation of brain synchrony to enhance brain function and rehabilitate faulty cognition in humans: A proof of concept

• Founded in 2014

• Coordinator: Antoni Valero Cabre

• The long-term goal of this project is to develop the use of non-invasive manipulation of abnormal cerebral oscillations underlying cognitive activity to restore brain function in neurological patients. Cognitive functions emerge from large distributed networks organized in space and time. The short-term goal of this application is to study the causal role played by oscillatory activity in visual awareness and test whether their manipulation by non-invasive brain stimulation has the potential to restore its function in stroke patients.

CATI (Alzheimer Plan)

Participants : Olivier Colliot [Correspondant] , Marie Chupin [Correspondant] , Stanley Durrleman, Didier Dormont, Chabha Azouani, Ali Bouyahia, Johanne Germain, Xavier Badé, Sonia Djobeir, Hugo Dary, Ludovic Fillon, Takoua Kaaouana, Alexandre Routier, Sophie Lecomte, Mathieu Dubois.

• Project acronym: CATI

• Project title: Centre d'Acquisition et de Traitement des Images

• Founded in 2011

• Amount: 9M€

• Coordinator: Jean-François Mangin

• Other partners: Neurospin, CENIR, Inserm U678, IM2A

• Abstract: The CATI project (funded by the National Alzheimer Plan for 9M€, 2.1M€ for ARAMIS) aims at creating a national platform for multicenter neuroimaging studies. CATI aims to be a national resource for the scientific, medical and industrial research community and will provide a wide range of services: access to a national acquisition network, standardization of acquisitions, image quality control, image analysis, databasing/archiving, meta-analyses. Through CATI, our team coordinates a large network composed of over 30 image acquisition centers. CATI already supports over 15 multicenter projects including the national cohort MEMENTO (2300 subjects). CATI is integrated with France Life Imaging (PI: F. Lethimonnier) and the Neugrid for you (N4U, PI: G. Frisoni) network.

National Networks

• GdR Statistics and Medicine - http://gdr.statsante.fr/Accueil.html

Other National Programs

Programme Hospitalier de Recherche Clinique (PHRC)

Participants : Olivier Colliot, Marie Chupin, Stanley Durrleman, Didier Dormont, Damien Galanaud.

• PHRC PredictPGRN, co-funding by Alzheimer Plan, Caractérisation multimodale prospective de la démence frontotemporale dûe à des mutations du gène PGRN à un stade symptomatique et présymptomatique. (Coordinator : A. Brice)

• PHRC ImaBio3, co-funding by Roche (pharmaceutical industry), Rôle des réactions cellulaires sanguines, inflammatoires et immunitaires anti-amyloïde centrales et périphériques dans la maladie d’Alzheimer débutante. (Coordinator : M. Sarazin)

• PHRC CAPP, Caractérisation linguistique, anatomique/métabolique et biologique des différentes formes d'aphasie primaire progressive : vers le rationnel pour des essais pharmacologiques et des rééducations du langage ciblées. (Coordinator: M. Teichmann)

Institut Universitaire d’Ingénierie pour la Santé (IUIS)

Participants : Mario Chavez, Xavier Navarro.

• Project acronym: DYSPEV

• Project title: Dépistage de la dyspnée par potentiels évoqués visuels

• Founded in 2014

• Amount: 38K€

• Coordinator: Thomas Similowski

• Other partners: UPMC, Inserm UMR 1158

• Abstract: Steady state visual evoked potentials (SSVEP) have been widely utilized in brain computer interfacing (BCI) in last years. In this project, we explore the possibilities of SSVEP to manage the communication between patients suffering from respiratory disorders and health care providers. By imposing different breathing constraints, we use a SSVEP-based brain computer interface to help those subjects to communicate their breathing sensations (breathing well/breathing bad).