Gray matter atrophy is associated with functional connectivity reorganization during the Paced Auditory Serial Addition Test (PASAT) execution in Multiple Sclerosis (MS)

Background and purpose: We explored the relationship between gray matter atrophy and reorganization of functional connectivity in multiple sclerosis patients during execution of the Paced Auditory Serial Addition Test (PASAT). Materials and methods: Seventeen patients and 15 healthy controls were selected for the study. Atrophy was determined using voxel-based morphometry, and atrophy-related connectivity changes were assessed using psychophysiological interaction analysis. Group differences, and correlations with PASAT performance and radiological variables were also examined. Results: Gray matter atrophy in MS patients was circumscribed to the bilateral posterior cingulate gyrus/precuneus. Compared with controls, patients showed stronger connectivity between the left posterior cingulate gyrus/precuneus, and the left middle temporal gyrus and left cerebellum. A regression analysis in controls showed a negative correlation between PASAT scores and functional connectivity between: (1) the left posterior cingulate gyrus/precuneus, and left pre/postcentral gyri and left occipital gyrus, and (2) the right posterior cingulate gyrus/precuneus, and bilateral cerebellum and left pre/postcentral gyri. Patients showed a negative correlation between brain parenchymal fraction and functional connectivity between the left posterior cingulate gyrus/precuneus and left cerebellum. Conclusion: Patients with early MS and little brain damage presented more connectivity during PASAT execution, which may be interpreted as compensatory processes that help preserve cognitive functions. This work was supported by the Brainglot project of the CONSOLIDER-INGENIO 2010 Program (grant number CSD2007-00012), a grant from MINECO (PSI2010-20168), a grant from Universitat Jaume I (P1 · 1B2011-09), and an edu- cational grant from Biogen Idec to CA.