CerCo
Centre de Recherche Cerveau & Cognition

IMPEC-Images and models for exploring the brain

Head : Caroline FONTA

Our main approach consists of multiscale and multimodal imaging as a basis for developing statistical and modeling tools to investigate cerebral physiological and pathological processes. We explore the different brain compartments: vessel and cortical tissue, at the macro and micro-scales in nonhuman primates and rodent models of Alzheimer’s disease and epilepsy. We are developing a nonhuman primate model of the aging brain combining various imaging techniques: NMR (protocols for brain structure, myelin content, vasculature), PET (metabolism, amyloid plaques, tau protein, NMDA receptors, inflammation…), XR (microtomography). More specifically, we are exploring in the marmoset monkey (Callithrix jacchus) brain anatomical markers of neurodegenerative diseases (AD) and vascular networks that we combine to analyze their relation with the monkey cognitive abilities (collaboration inside Cerco with Florence Rémy (team MAOs) and Pascal Girard (team C3P)). Each imaging modality deals with one scale, one resolution, and one type of information. In addition to image registration, we are investigating multimodal data fusion approaches to combine anatomical and functional data in joint analysis and uncover both shared and distinct brain aging markers. Other methods (geodesic PCA merged with machine learning algorithm) are developed with IMT and ENAC collaborators to assess which optimal combination of MRI biomarkers (brain volume, diffusion indices, magnetization transfer ratio) can improve their predictive value in the context of a multi-center and multimodal Multiple sclerosis (MS) trial.
Furthermore, we contribute to a project initiated at IMFT to simulate cerebral blood flow autoregulation in its craniospinal environment. We are investigating MRI-based techniques to identify arterial and venous systems topology and geometry in the marmoset brain and flow in the blood and the CSF compartments. Such anatomical data will be used to develop and parameterize a blood flow model for the marmoset in the context of preclinical analysis. The ultimate objectives are a simulator tool and a clinical protocol, using the autoregulation time course pattern to infer the clinical status of the craniospinal system and its aging process in humans.
In collaboration with Lionel Nowak (team PAF), we develop a research program on adenosine and ectonucleotidases (more precisely on the Tissue Non-specific Alkaline Phosphatase –TNAP-) in the cerebral cortex. Adenosine, through its functions in synaptic plasticity and inflammatory processes, is likely to be involved in multiple cerebral pathologies such as epilepsy, Alzheimer’s disease, and ischemia. To study adenosine sources and functions, we develop several approaches: a « metabolomic » and a biochemical analysis using TNAP-KO mice, brain slices, and neurons in culture treated with ectonucleotidase inhibitors or overexpressing TNAP, and electrophysiological experiments using brain slices maintained in vitro.

Main external collaborators
  • Pierre Payoux, Franck Desmoulin, Anne Sophie Brun-Salabert (Tonic INSERM 1214, Toulouse)
  • Moktar Zagzoule, Patricia Cathalifaud, Franck Plouraboué (Institute of Fluid Mechanics, Toulouse)
  • Laurent Risser, Pierre Maréchal (Institute of Mathematics, Toulouse)
  • Stéphane Puechmorel (ENAC, Toulouse)
  • Denis Kouame, Adrian Basarab (IRIT, Toulouse)
  • Véronique Gilard (LSPCMIB, Biomedical NMR group; University of Toulouse)
  • David Magne (ICBMS, University of Lyon)
  • Etienne Mornet (Hospital-University Center, Versailles)
  • Jose Luis Millan (Burham Institute, La Jolla, CA, USA
  • Marcello Rosa (Department of Physiology, Monash University, Australia)

Research themes
  • Ageing brain in non human primate
  • Cerebral vascularisation
  • Ectonucleotidases, synaptic transmission, inflammation

Permanent research staff
  • Isabelle BERRY
  • Caroline FONTA
  • Muriel MESCAM
PhD student
  • Farah BAZZI
  • Adrien MARQUE
Post-doc fellow
  • Germain ARRIBARAT
Recent representative publications
  • Bessueille L, Briolay A, Como J, Mebarek S, Mansouri C, Gleizes M, El Jamal A, Buchet R, Dumontet C, Matera EL, Mornet E, Millan JL, Fonta C, Magne D. (2020). Tissue-nonspecific alkaline phosphatase is an anti-inflammatory nucleotidase. Bone. 133:115262. doi: 10.1016/j.bone.2020.115262.
  • De Jager EJ, Van Schoor AN, Hoffman JW, Oettle AC, Fonta C, Mescam M, Risser L, Beaudet A (2019). Sulcal pattern variation in extant human endocasts. Journal of Anatomy 235(4):803-810. http://doi.org/10.1111/joa.13030.
  • Risser L, Sadoun A, Mescam M, Strelnikov K, Lebreton S, Boucher S, Girard P, Vayssière N, Rosa MGP, Fonta C. (2019). In vivo localization of cortical areas using a 3D computarized atlas of the marmoset. Brain Struct Funct 224(5):1957-1969. doi: 10.1007/s00429-019-01869-x.
  • Bazzi F, Mescam M, Basarab A, Kouame D. On Single-Image Super-Resolution in 3D Brain Magnetic Resonance Imaging. Annu Int Conf IEEE Eng Med Biol Soc. 2019 Jul;2019:2840-2843. doi: 10.1109/EMBC.2019.8857959. PMID: 31946484.
  • Rodriguez-Callejas JDD, Cuervo-Zanatta D, Rosas-Arenallo A, Fonta C, Fuchs E, Perez Cruz C. 2019. Loss of ferritin-positive microglia relates to increased iron, RNA oxidation and dystrophic microglia in brain of aged male marmoset. American Journal of Primatology e22956.doi: 10.1002/ajp.22956.
  • Perrier S, Gleizes M, Fonta C, Nowak L. 2019. Effect of adenosine on short-term synaptic plasticity in mouse piriform cortex in vitro: adenosine acts as a high-pass filter. Physiological Reports, 7 (3), e13992, https://doi.org/10.14814/phy2.13992.
  • Sadoun A, Rosito M, Fonta C, Girard P. 2019. Key periods of cognitive decline in a nonhuman primate model of cognitive aging, the common marmoset (Callithrix jacchus). Neurobiology of Aging 74:1-14.
  • Rebbah S, Delahaye D, Puechmorel S, Maréchal P, Nicol F, Berry I. (2019). Classification of Multiple Sclerosis patients using a histogram-based K-Nearest Neighbors algorithm. OHBM 2019, 25th annual meeting of Organization for Human Brain Mapping, Jun 2019, Rome, Italy.
  • Rebbah S, Delahaye D, Puechmorel S, Nicol F, Maréchal P, Berry I. (2018). A combined MRI biomarker approach using a non-standard multiple factor analysis. CISP-BMEI 2018, 11th International Congress on Image and Signal Processing, BioMedical Engineering and Informatics18, Beijing, China. pp.art. no. 8633261
  • Kennel P, Fonta C, Guibert R, Plouraboué F. 2017. Analysis of vascular homogeneity and anisotropy on high-resolution primate brain imaging. Human Brain Mapping 38(11):5756-5777.
  • Cruz T, Gleizes M, Balayssac S, Mornet E, Marsal G, Millán JL, Malet-Martino M, Nowak LG, Gilard V, Fonta C. 2017. Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis. J Neurochem 140:919-940.
  • Sadoun A, Strelnikov K, Bonté E, Fonta* C, Girard* P 2015. Cognitive impairment in a young marmoset reveals lateral ventriculomegaly and a mild hippocampal atrophy: a case report. Scientific Reports Nov 3;5:16046. doi: 10.1038/srep16046. *equal contribution.
  • Salabert AS, Fonta C, Fontan C, Adel D, Alonso M, Pestourie C, Belhadj-Tahar H, Tafani M, Payoux P. 2015. Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors. Nuclear Medicine and Biology 42: 643-653.
  • Book : Caroline Fonta and László Négyessy (Eds) 2015. Neuronal Tissue-Nonspecific Alkaline Phosphatase (TNAP), Subcellular Biochemistry, Vol. 76. Springer ISBN 978-94-017-7196-2, DOI 10.1007/978-94-017-7197-9. 350pp