Multiple sclerosis reduces synchrony of the magnocellular pathway

Abstract

Multiple Sclerosis (MS) is an autoimmune demyelinating disease that damages the insulation of nerve cell fibers in the brain and spinal cord. In the visual system, this demyelination results in a robust delay of visually evoked potentials (VEPs), even in the absence of overt clinical symptoms such as blurred vision. VEPs, therefore, offer an avenue for early diagnosis, monitoring disease progression, and, potentially, insight into the differential impairment of specific pathways. A primary hypothesis has been that visual stimuli driving the magno-, parvo-, and konio-cellular pathways should lead to differential effects because these pathways differ considerably in terms of myelination. Experimental tests of this hypothesis, however, have led to conflicting results. Some groups reported larger latency effects for chromatic stimuli, while others found equivalent effects across stimulus types. We reasoned that this lack of pathway specificity could, at least in part, be attributed to the relatively coarse measure of pathway impairment afforded by the latency of a VEP. We hypothesized that network synchrony could offer a more sensitive test of pathway impairments. To test this hypothesis, we analyzed the synchrony of occipital electroencephalography (EEG) signals during the presentation of visual stimuli designed to bias activity to one of the three pathways. Specifically, we quantified synchrony in the occipital EEG using two graph-theoretic measures of functional connectivity: the characteristic path length (L; a measure of long-range connectivity) and the clustering coefficient (CC; a measure of short-range connectivity). Our main finding was that L and CC were both smaller in the MS group than in controls. Notably, this change in functional connectivity was limited to the magnocellular pathway. The effect sizes (Hedge’s g) were 0.89 (L) and 1.26 (CC) measured with magno stimuli. Together, L and CC define the small-world nature of a network, and our finding can be summarized as a reduction in the small-worldness of the magnocellular network. We speculate that the reduced efficiency of information transfer associated with a reduction in small-worldness could underlie visual deficits in MS. Relating these measures to differential diagnoses and disease progression is an important avenue for future work.