Multiple Sclerosis (MS) is a chronic autoimmune and inflammatory disease that affects the myelin sheathing of axons, causing motor, sensory and cognitive deterioration, and is one of the world?s most common neurological disorders affecting the Central Nervous System. The loss of brain matter (atrophy) and the development of brain lesions have been extensively studied using brain imaging techniques such as Magnetic Resonance Imaging (MRI), and there is evidence that these alterations might be associated with cognitive impairment. However, the physiological outcomes of this pathology affecting neuronal activity and axonal conduction have been less explored. Given the pathophysiology of MS and the crucial role myelin plays in the fast communication between distant neuronal populations, MS is likely to affect highly coordinated neuronal activity, such as coherent cortical oscillations. These oscillations are responsible for the communication between distant brain regions, which through their concerted activity gives rise to brain networks. There is a growing interest in studies of human brain networks using resting-state functional MRI (fMRI). However, it is unclear whether brain networks measured during resting-state exhibit comparable properties during task performance. Understanding the networks? functional communication is crucial to provide important clues for the pathophysiology of the disease, as well as to detect biomarkers related to the mechanisms that are responsible for MS disease progression. We will investigate for the first time neuronal connectivity measures in patients with MS during task performance at concurrent high spatial and temporal resolution with coregistered EEG-fMRI. This is a technical and a scientific advance in this area, as there are to this date no reliable biomarkers of the disease, and a scientific challenge, that we are confident can be accomplished given our group?s technical expertise in multimodal imaging. We will investigate structural and functional neuroimaging biomarkers of connectivity between brain regions, intra- and inter-hemispherically, both during resting-state and importantly during task performance. We will take advantage of a visual motion paradigm of perceptual decision yielding long-range integration of information, which depends strongly on the communication between distant brain regions.  Our hypothesis is that the perceptual dynamics of our paradigm might be altered in patients with MS, due to changes in neuronal communication.
These functional biomarkers might be of keen interest in the investigation of alterations in brain communication with pharmacological treatment (e.g. with remyelinating factors). Another objective will be to compare functional connectivity measures in patients with MS at two different time points, before and after treatment with fingolimod, to investigate the potential improvement of network communication and its correlation with cognitive benefits.