The functional substrates of deficits of executive function (EF), a relevant disabling symptom in MS patients, have been scarcely investigated.
To investigate changes of resting state (RS) functional connectivity (FC) in patients with MS and their correlation with neuropsychological measures related to EF.
High-resolution T1-weighted and RS functional MRI (fMRI) scans were acquired from 116 MS patients and 65 matched healthy controls (HC). All subjects underwent a neuropsychological evaluation, including the computerized version of the Wisconsin Card Sorting Test (WCST), a multidimensional EF assessment. MS patients also underwent a clinical evaluation, including the expanded disability status scale (EDSS). RS FC was assessed using a seed-voxel correlation analysis. Seed regions relevant for EF were derived from the literature: left (L) inferior parietal sulcus (IPS), L frontal pole (FP) and right (R) cerebellum (Crus I and II). We used SPM and voxel-wise models to compare RS FC between MS patients and HC within the identified networks. Then, associations between RS FC and age- and education-corrected WCST scores and EDSS were evaluated.
Twenty-five (21.5%) MS patients failed the WCST. Compared to HC, MS patients showed significantly decreased RS FC of the L IPS with bilateral middle frontal, L middle temporal and L cerebellar regions, as well as increased RS FC of the L IPS with bilateral thalami. MS patients also exhibited decreased RS FC between the L FP and superior parietal regions. A widespread RS FC decrease was found in MS vs HC between the R Crus I/II and bilateral cerebellar regions and fronto-parietal cortices. Significantly increased RS FC was finally detected between the R Crus I/II and the bilateral orbitofrontal cortex. In MS patients, significantly increased RS FC between the R Crus I/II regions and the orbitofrontal cortex was associated with better performance at the WCST (r=range 0.19-0.27, p=range 0.03-0.003). Conversely, decreased fronto-cerebellar and parieto-cerebellar RS FC was correlated with higher EDSS score (r=range -0.19 to -0.35, p=range 0.03-<0.001).
In an MS group relatively spared by relevant EF deficits, increased RS FC strength in EF-related functional networks was detected. The association between increased RS FC and better WCST scores suggests a compensatory role of detected RS FC abnormalities in these patients.