Cognitive rehabilitation correlates with the functional connectivity of the anterior cingulate cortex in patients with multiple sclerosis

We investigated how resting state (RS) functional connectivity (FC) of the anterior cingulate cortex (ACC) correlates with cognitive rehabilitation in relapsing remitting multiple sclerosis (RRMS) patients. A neuropsychological assessment and RS fMRI at baseline and after 12 weeks were obtained from 20 RRMS patients, who were assigned randomly to undergo treatment (n = 10) (treatment group-TG), which entailed computer-assisted cognitive rehabilitation of attention/information processing and executive functions for 3 days/week, or not to receive any cognitive rehabilitation (n = 10) (control group-CG). Voxel-wise changes of ACC RS FC were assessed using SPM8. In both groups, at the two study time points, ACC activity was correlated with the bilateral middle and inferior frontal gyrus, basal ganglia, posterior cingulate cortex, cerebellum, precuneus, middle temporal gyrus, and inferior parietal lobule (IPL). At follow up, compared to baseline, the TG showed an increased FC of the ACC with the right middle frontal gyrus (MFG) and right IPL, while the CG showed a decreased FC of the ACC with the right cerebellum and right inferior temporal gyrus (ITG). A significant treatment x time interaction was found for the increased FC of the right IPL and for the decreased FC of the right ITG. In the TG only, significant correlations (p < 0.001) were found between improvement of PASAT performance and RS FC of the ACC with the right MFG (r = 0.88) and right IPL (r = 0.76). In MS, cognitive rehabilitation correlates with changes in RS FC of brain regions subserving the trained functions. fMRI might be useful to monitor rehabilitative strategies in MS.