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Although functional connectivity has been extensively studied in MS, robust estimates of both stationary (static connectivity at the time) and dynamic (connectivity variation across time) functional connectivity has not been commonly evaluated and neither has its association to cognition. In this study, we focused on interhemispheric connections as previous research has shown links between anatomical homologous connections and cognition. We examined functional interhemispheric connectivity (IC) in MS during resting-state functional MRI using both stationary and dynamic strategies and related connectivity measures to processing speed performance. Twenty-five patients with relapsing-remitting MS and 41 controls were recruited. Stationary functional IC was assessed between homologous Regions of Interest (ROIs) using correlation. For dynamic IC, a sliding window approach was used to quantify changes between homologous ROIs across time. We related IC measures to cognitive performance with correlation and regression. Compared to control subjects, MS demonstrated increased IC across homologous regions, which accurately predicted performance on the symbol digit modalities test (SDMT) ( R  2  = 0.96) and paced auditory serial addition test (PASAT) ( R  2  = 0.59). Dynamic measures were not different between the 2 groups, but dynamic IC was related to PASAT scores. The associations between stationary/dynamic connectivity and cognitive tests demonstrated that different aspects of functional IC were associated with cognitive processes. Processing speed measured in SDMT was associated with static interhemispheric connections and better PASAT performance, which requires working memory, sustain attention, and processing speed, was more related to rigid IC, underlining the neurophysiological mechanism of cognition in MS.

Both Stationary and Dynamic Functional Interhemispheric Connectivity Are Strongly Associated With Performance on Cognitive Tests in Multiple Sclerosis