Structural and functional MRI correlates of cognitive impairment in patients with multiple sclerosis

Cognitive impairment in MS is common and tends to affect executive functions, working memory and attention. The mechanisms of cognitive impairment and the significance of compensatory processes in the central nervous system (CNS) in MS-patients are not well understood. In the current study, we analyzed mildly disabled patients with relapsing-remitting MS and matched control subjects with a neuropsychological test battery, voxel-based morphometry (VBM) and functional MRI. Patients showed reduced performance compared to healthy control subjects on tests of working memory and executive function. Performance on the fMRI delayed recognition task was similar in the two groups. Contrary to T2 lesion load, cortical atrophy correlated with performance on the PASAT, reference test for the evaluation of cognitive function in MS. Cortical volume was reduced in the patient group overall in left prefrontal and temporal cortex compared with the control group. In a subgroup of patients with low cognitive performance, cortical atrophy was more extensive in bilateral frontal and temporal cortex as well as bilateral parietal cortex indicating a close association between cortical atrophy and cognitive impairment. During performance of the fMRI task, patients overall exhibited more activation in left parietal cortex than healthy controls. The subgroup of patients with normal cognitive performance exhibited more activation in left prefrontal and parietal cortex and greater task-related deactivation in medial prefrontal cortex and left hippocampus than matched control subjects. Both cortical atrophy and T2 lesion load were associated with enhanced activation in dorsolateral prefrontal cortex; T2 lesion load also correlated with activation in left parietal cortex, whereas cortical atrophy was associated with enhanced activation in dorsal anterior cingulate cortex (ACC)as well as with reduced task-related deactivation in rostral ACC/superior frontal gyrus and left hippocampus. The finding that both structural damage and high performance were associated with increased prefrontal activation indicates that structural damage elicits compensatory processes in MS-patients, though cortical atrophy appears to limit the capacity for compensation even at early stages of the disease.