Distinct mechanisms of altered cerebral activation in patients with multiple sclerosis

Cognitive impairment in multiple sclerosis is common and affects patients early in the course of the disease. Cerebral plasticity may limit the effects of CNS tissue damage on cognition. Here we compared fMRI activation patterns in a group of 19 mildly disabled MS patients and 19 matched control subjects during performance of a delayed recognition task. Moreover, we investigated the relationship between brain activation and neuropsychological test results as well as structural MR measures of disease severity. Results were analyzed using a random effects analysis (SPM2). Patients overall showed more activation than control subjects in left inferior frontal gyrus (IFG) and a tendency towards more activation in left mid-frontal gyrus (MFG), insula and inferior parietal cortex (IPL). A subgroup of patients with high performance on the PASAT, a comprehensive measure of cognitive function and reference task for the cognitive evaluation of MS-patients, exhibited significantly more activation than matched control subjects in all these regions, whereas activation patterns for patients with low performance and their matched controls did not differ. In a multiple regression analysis of the patient group, including white matter lesion volume and cortical volume as regressors, white matter lesion volume as well as cortical volume correlated positively with brain activation in a similar network of prefrontal, frontal medial wall and parietal regions. Control subjects did not show an association between cortical volume and cerebral activation. White matter lesion volume did not correlate with cortical volume in the patient group. Contrary to white matter lesion volume, cortical volume showed a correlation with performance on the PASAT. These results suggest that changes in brain activation in MS-patients reflect distinct disease-mediated factors. Cerebral plasticity may reduce the effects of focal white matter tissue damage and thus help preserve cognitive function in MS-patients. Cortical atrophy, however, might limit the capacity for cortical reorganization even at early stages of the disease.