Functional Cognitive Control Load in Multiple Sclerosis (P4.127)

Objective: To investigate clinical, behavioural and fMRI correlates of N-back task performance in relapse-onset multiple sclerosis (MS) patients. Background: The ability to maintain current task goals and reducing additional processing of irrelevant information crucial for cognitive performance. Methods: A block-design N-back fMRI task was administered to 72 MS patients (12 clinically isolated syndromes [CIS], 38 relapsing-remitting [RR], 22 secondary progressive [SP]) and 24 age- and gender-matched healthy controls (HC). Load-dependent activations/deactivations with increasing task difficulty (0- to 3-back and LOAD contrasts) were modelled using SPM8. Correlation with clinical and behavioural measures were performed. Results: Compared to HC, MS patients had worse task performance and brain atrophy. All groups activated fronto-parietal and cerebellar regions and deactivated areas of the default-mode network (DMN). Compared to HC, MS patients had higher recruitment of right parietal cortex and fronto-mesial areas during low cognitive load conditions and decreased recruitment of posterior regions during higher load conditions. During the LOAD contrast, compared to HC and RRMS, CIS patients had increased activations of anterior brain areas and right hippocampus and decreased recruitment of left postcentral and superior temporal (STG) gyri. SPMS patients showed decreased activation of left putamen when compared to RRMS. Worse performance at attentional domain correlated with lower right precuneus recruitment, whereas higher global cognitive score was related to decreased deactivations of right STG. Conclusions: Load-dependent alterations of executive network recruitment occur in MS and vary according to disease phenotype. Increased recruitment of frontal regions was associated to early phase of MS. The modulation of regions belonging to the DMN is more evident in patients with long-lasting disease and is related to the global cognitive profile, suggesting an increased need of cognitive resources to cope with task-demand. Partially supported by grants from Italian Ministry of Health (GR-2008-1138784/GR-2009-1529671) and Fondazione Italiana Sclerosi Multipla (FISM2012/R/8).