To investigate resting state (RS) functional connectivity (FC) changes in multiple sclerosis (MS) and their correlation with executive function (EF) neuropsychological measures.

EF dysfunction is a relevant disabling symptom in MS, potentially associated with brain functional reorganization.

3D T1-weighted and RS fMRI 3.0T scans were acquired from 116 MS patients and 65 healthy controls (HC). Subjects underwent neuropsychological and clinical evaluation, including computerized Wisconsin Card Sorting Test (WCST) and the Expanded Disability Status Scale (EDSS) score. RS FC was assessed using seed-voxel correlation analysis with following EF-relevant seeds: left (L) and right (R) intraparietal sulcus (IPS), frontal pole (FP) and cerebellum (Crus I and II). SPM voxel-wise models were used for RS FC between-group comparisons. Then, associations of RS FC with WCST (age- and education-corrected) and EDSS scores were evaluated.

Twenty-five (21.5%) MS patients failed at the WCST. Compared to HC, MS patients showed significantly decreased RS FC of the bilateral IPS with bilateral middle frontal, L middle temporal and L cerebellar regions, as well as increased RS FC with bilateral thalami. MS patients also exhibited decreased RS FC between L-FP and superior parietal regions. A widespread RS FC decrease was found in MS vs HC between L- and R-Crus I/II and bilateral cerebellar regions and fronto-parietal cortices. Significantly increased RS FC was finally detected between L- and R-Crus I/II and bilateral orbitofrontal cortex. In MS, significantly increased RS FC between R-Crus I/II regions and the orbitofrontal cortex was associated with better WCST performances (r=range 0.19/0.27, p=range 0.03-0.003), while decreased fronto-cerebellar and parieto-cerebellar RS FC was correlated with a higher EDSS score (r=range -0.19/-0.35, p=range 0.01-<0.001).

In an MS group relatively spared by EF deficits, increased RS FC in EF-related networks was associated with better WCST scores, suggesting a compensatory role of RS FC abnormalities.