Consistent Decreased Functional Connectivity Among the Main Cortical and Subcortical Functional Networks in MS: Relationship With Disability and Cognitive Impairment (P6.133)

OBJECTIVE: To explore resting state (RS) functional connectivity (FC) abnormalities within the main cortical/subcortical brain networks in a large cohort of patients with MS with different clinical phenotypes. BACKGROUND: Previous RSFC studies in healthy individuals have identified seven major functional “hubs”, each associated with a functional brain network: there are four cortical networks (default mode, dorsal attention, visual and somatosensory) and three subcortical networks (associated with thalamus, amygdala and cerebellum). DESIGN/METHODS: RS fMRI and a complete neuropsychological evaluation were obtained from 202 MS patients (118 relapsing-remitting [RR], 43 secondary progressive [SP], 28 benign and 13 primary progressive MS) and 98 healthy controls. RSFC analysis was done using a seed-voxel correlation with seven major cortical/subcortical hubs (posterior cingulum, inferior parietal cortex, cuneus, postcentral gyrus, cerebellum, thalamus, and amygdala). Between-group differences of RSFC and correlations with clinical/neuropsychological scores were evaluated (SPM8). RESULTS: Compared to controls, MS patients showed a widespread reduction of RSFC in all cortical/subcortical networks. In the visual and somatosensory networks, RSFC decrease was mainly found in bilateral parietal and superior occipital regions. RSFC decrease within the default and dorsal attention network involved the bilateral precuneus and superior/middle frontal regions. Decreased cerebellar RSFC was observed in the dorsal attention, thalamic and cerebellar networks. A decreased RSFC between the thalamus and frontal regions was also detected. Compared to RRMS, SPMS patients showed reduced RSFC in the somatosensory and thalamic networks. Decreased cerebellar RSFC was correlated with higher EDSS. Decreased RSFC in frontal regions of the dorsal attention and default networks correlated with worse cognitive performances. CONCLUSIONS: Cortical/subcortical RSFC is consistently reduced in MS patients and is clinically relevant, since it correlates with disability and cognitive impairment. Study Supported by: Partially supported by a grant from Italian Ministry of Health (GR-2009-1529671).