Altered cortical phase- and amplitude-coupling in Multiple Sclerosis

Multiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related functional changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. Here, we measured magnetoencephalography in 17 relapsing-remitting Multiple Sclerosis patients at an early disease stage (median EDSS = 1.5, range 0 to 3.5) and 17 healthy controls to investigate brain-wide phase- and amplitude-coupling of frequency specific neuronal activity. We developed a new analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to identify changes of brain-wide coupling in Multiple Sclerosis. We identified systematic and non-redundant changes of both phase- and amplitude-coupling. Changes included both, increased and decreased neuronal coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. Our results unravel systematic changes of large-scale neuronal coupling in Multiple Sclerosis and suggest non-invasive electrophysiological coupling measures as powerful biomarkers of Multiple Sclerosis.