Distributed changes in resting-state networks functional connectivity in multiple sclerosis: correlation to SDMT performance

Background: Multiple sclerosis (MS) is a chronic, inflammatory and neurological disorder, which causes severe debilitation impacting on patient quality of life. The symptoms of MS include both physical and cognitive impairment. Different studies highlighted the presence of functional impairments of resting-state networks in this disease. Methods: In this study we investigate the resting-state brain network impairments using functional MRI (fMRI) in a cohort of 37 clinically isolated syndrome (CIS) patients in comparison to a group of 14 healthy controls (HCs), matched for age and sex. All CIS participants underwent neurological and neuropsychological evaluation, including the Symbol Digit Modalities Test (SDMT). Data were collected at the beginning of study (baseline level), and after 6, 12, and 36 months. fMRI alterations were estimated using seed-to-voxel analysis in CONN to create seed-based connectivity maps, which were subsequently used to carry out multiple group analysis of relative functional connectivity . Results: During the first scanner, significant connectivity differences between the CIS group and the HC group in different RSNs seeds located in a variety of cortical regions were found.The CIS group showed especially reduced FC compared to HC group. Then, within the CIS group, we found that an increased connectivity in all the RSNs was correlated with lower SDMT z-score, indicating worse cognitive performance on the test. Afterwards, we confronted the FC levels in the two groups at the baseline scanner and the 1 year follow-up. The MS group showed both reduction and increase in FC at 1 year follow-up compared to baseline in different RSNs. We then tested to see whether some brain regions and their connectivity at the baseline scan may be correlated with the results of the SDMT at the follow-up of 1 year. Our data shows higher connectivity between in different RSNs correlated with SDMT scores of 1 year later, meanwhile some other regions correlated negatively. Conclusions: These results suggest that functional connectivity in resting-state brain networks in the MS group is disrupted already at the first stages of the disease and it evolves over time. Our results also indicate a correlation between these alterations and cognitive impairments in MS patients.