• Gianna C Riccitelli, Elisabetta Pagani, Mariaemma Rodegher, Bruno Colombo, Paolo Preziosa, Andrea Falini, Giancarlo Comi, Massimo Filippi, and Maria A Rocca.
• Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy.
• Mult. Scler. 2019 Feb 1; 25 (2): 204-216.

ObjectivesTo map the regional patterns of white matter (WM) microstructural abnormalities and gray matter (GM) atrophy exclusively associated with reduced performance in the Symbol Digit Modalities Test (SDMT) and Paced Auditory Serial Addition Test (PASAT) in relapsing-remitting (RR) multiple sclerosis (MS) patients.MethodsIn all, 177 RRMS patients and 80 healthy controls (HC) were studied. WM microstructural abnormalities were investigated on diffusion tensor images using tract-based spatial statistics analysis, and regional GM atrophy was estimated on three-dimensional (3D) T1-weighted images using voxel-based morphometry.ResultsCompared to HC, RRMS patients showed the expected pattern of cortical-subcortical GM atrophy and WM microstructural abnormalities. In patients, diffusivity abnormalities of supratentorial WM tracts correlated with both SDMT and PASAT scores. Lower SDMT performance was also associated with WM damage in several infratentorial WM tracts. Lower SDMT scores correlated with atrophy of the right anterior cingulate cortex, left postcentral gyrus, and right middle temporal gyrus, whereas lower PASAT scores correlated with atrophy of the deep GM nuclei, bilaterally, and several fronto-temporo-occipital regions.ConclusionIn RRMS patients, regional damage of different neural systems helps explaining reduced performance in SDMT and PASAT. WM microstructural damage typified reduced SDMT performance, whereas atrophy of several GM regions distinguished reduced PASAT performance.

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