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Thesis defense – Ismail Koubiyr

17 September 2019 / 14:30

Venue: Salle module 2.6

Team : Glia-neuron interactions
Neurocentre Magendie

Thesis supervisor: Pr. Bruno Brochet


Cognitive impairment is frequent in multiple sclerosis (MS) but its underlying mechanisms are still poorly understood. MRI techniques have been a valuable tool to investigate the biological substrates of cognitive processes. The objective of this thesis was to better understand the pathophysiological mechanisms of cognitive functioning at the early stage of MS. We followed clinically isolated syndrome (CIS) patients for one year, using neuropsychological tests, conventional and more advanced MRI techniques. We first demonstrated a differential gray matter vulnerability at the beginning of MS with a pathological spread from the hippocampus towards the cortex. We showed that the first microstructural alterations taking place within the hippocampus were able to predict its future volume loss. After that, we were interested in the potential brain functional reorganization at this stage of the disease. Using resting-state functional MRI, we were able to demonstrate very early regional brain functional reorganization starting from the disease onset and becoming more pronounced after one year of evolution. We also noticed a preservation of cognitive performances in CIS patients, which we found was associated to more functional reorganization. These results suggested then a compensation mechanism at the first year after a CIS. However, the relationship between these functional changes and the underlying anatomy was still missing. Thus, we combined resting-state functional MRI and diffusion tensor imaging to represent both functional and structural connectivity. Using the structural-functional coupling parameter, representing the association between structural and functional connections, we showed a decoupling one year after the disease onset in three major networks (salience, visual and somatomotor networks). This decoupling was noticed while cognitive performances were preserved and functional reorganization present. These last results led us to suggest that the functional reorganization at this stage, acting as a compensation mechanism, occurs along indirect anatomical pathways. In order to confirm these results and further follow-up brain networks topology and its impact on cognition, we are currently calling back our CIS patients for their 5-year visit.

Keywords: Multiple sclerosis, MRI, clinically isolated syndrome, connectivity, functional MRI, diffusion tensor imaging.


1. Koubiyr I, Besson P, Deloire M, Charré-Morin J, Saubusse A, Tourdias T, Brochet B and Ruet A (2019) Dynamic modular-level alterations of structural-functional coupling in clinically isolated syndrome. Brain. doi: 10.1093/brain/awz270

2. Koubiyr I, Deloire M, Besson P, Coupé P, Dulau C, Pelletier J, Tourdias T, Brochet B, Ranjeva JP and Ruet A (2018) Longitudinal Study of Functional Brain Network Reorganization in Clinically Isolated Syndrome. Mult Scler. 1–13. doi: 10.1177/135245851881310814

3. Koubiyr I, Deloire M, Coupé P, Dulau C, Besson P, Moroso A, Planche V, Tourdias T, Brochet B and Ruet A (2018) Differential Gray Matter Vulnerability in the 1 Year Following a Clinically Isolated Syndrome. Front. Neurol. 9:824. doi: 10.3389/fneur.2018.00824

4. Planche V, Koubiyr I, Romero J.E, Manjon J.V, Coupé P, Deloire M, Dousset V, Brochet B, Ruet A and Tourdias T (2018) Regional hippocampal vulnerability in early multiple sclerosis: dynamic pathological spreading from dentate gyrus to CA1. Human Brain Mapping. doi: 10.1002/hbm.23970


Pr. Iris-Katharina Penner, Heinrich Heine University, Düsseldorf. Rapporteur
Dr. Menno M. Schoonheim, VU University Medical Center, Amsterdam. Rapporteur
Pr. Charles R.G. Guttmann, Harvard University, Boston. Examinateur
Dr Céline Louapre, Université Paris-Sorbonne. Examinatrice
Dr. Gwenaëlle Catheline, Université de Bordeaux. Examinatrice
Dr. Lucina Q. Uddin, University of Miami, Miami. Examinatrice invitée

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17 September 2019
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