University Hospital Münster
Department of Neurology with Institute of Translational Neurology

Author Of 1 Presentation

Imaging Poster Presentation

P0601 - Longitudinal functional modularisation and causality dynamics during de- and remyelination (ID 1715)

Abstract

Background

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), one of its pathophysiological hallmarks is demyelination, which is known to be involved in neurodegenerative mechanisms.

Objectives

Modular architecture and its dynamic adaptation could play a critical role in achieving flexible alterations of cerebral network architecture during de- and remyelination which is still not fully elucidated.

Methods

We address dynamic adaptation to cuprizone model of general de- and remyelination and ask if network community organization can relate to the longitudinal time events. To start with baseline and then by introducing cuprizone into the diet of mice we induced full CNS demyelination by targeting oligodendrocytes, over a period of 5 weeks (two time points). A subsequent myelin synthesis was allowed over reintroduction of normal food (two time points). To identify the modular organization the resting state fMRI within the graph theory framework was analyzed from each of the five time points. The dynamic network reconfiguration was estimated by flexibility as parameter of modularity allegiance and effective connectivity analyses were applied to test the causality of network dynamics between the identified modules.

Results

We found six modules namely default mode network (DMN), hippocampus, thalamus, lateral cortical network, basal forebrain and ventral mid brain. Interestingly the dynamics of de- and remyelination was mirrored by an initial significant increase in flexibility values and a return to baseline in the hippocampus (F(4, 80) = 22.8, p < 0.001), DMN (F(4, 80) = 36.5, p < 0.001) and thalamus (F(4, 80) = 24.5, p < 0.001). The other three networks showed a reversed pattern. The strength of connections from the hippocampus to DMN was associated with the behavioral indicators of memory novel object recognition (NOR) (r2 = 0.3854, p < 0.001) and thalamus to hippocampus to locomotor activity (r2 = 0.3144, p < 0.001).

Conclusions

Taken together, our fMRI modular analyses showed that global modularity and flexibility partially compensate for demyelination. Dynamics of compensation could be identified as modular specific (i.e. hippocampus, thalamus and DMN) at different intermediate time points, supporting the hypothesis that altered thalamocortical connectivity is an early pathological hallmark of the disease. Causality dynamics also provide biomarkers for evaluating the course of MS and disease dynamics.

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