Cortical graphs and brain disconnectiont in multiple sclerosis

Abstract

Degenerative processes are considered to be more important in the progression of neurological deficit in multiple sclerosis (MS) than the isolated recurrence of inflammatory and demyelinating events. Although the accumulation of macroscopic plaques in MS is a definite marker to the establishment of MS diagnosis, the degeneration seems to have stronger correlations with atrophy and disorganization of brain connections. Conventional magnetic resonance imaging (MRI) is not capable to accurately assess the variability of cerebral cortical folding patterns and the complex anatomical organization of the brain. Furthermore, the traditional scale used to measure disability in MS, the Expanded Disability Status Scale (EDSS), is strongly weighted through locomotor disability and do not precisely describe the whole spectrum of neurological impairment in the disease, being insufficient to characterize the clinical status associated to brain disconnection.Recently, advanced neuroimaging techniques are being developed to study anatomical and functional connectivity, developing models of neuronal networks, aiming to reconstruct the human connectome. Resting State functional functional MRI (fMRI) have observed synchronous spontaneous low-frequency blood oxygenation level dependent (BOLD) fluctuations that have been taken to reflect functional connectivity in the human brain. In the same way, there are coordinated patterns of cortical morphology that can be described as graphs. In this model, the cortical nodes are considered to be connected when they covary in thickness or volume.Using diffusion tensor imaging (DTI), it is possible to characterize the white matter networks associated to the nodes of functional synchronization or anatomic similarities between cortical areas, helping to reconstruct a global map of brain connections. As far as we know, the different methods of MRI suited to perform connectivity studies are being studied isolated, being poorly understood if these network analysis convert in similar results. The aim of this study is to perform a multiparametric approach of brain connectivity in MS, with functional and structural information, applying graph analysis in resting state fMRI and high resolution structural MRI (cortical graphs), combined with DTI tractography and correlating with detailed cognitive and clinical measurements. With this approach we believe that is possible to provide innovative data unraveling critical features enrolled in the degenerative processes and neurological decline in MS.