Cortical reorganization in multiple sclerosis (MS) is defined as a compensatory mechanism which requires MS patients to overactivate specific brain areas in order to perform the task as controls. To investigate this process with the Paced Auditory Serial Addition Test (PASAT) task, we selected 15 MS patients who performed the PASAT task within-normal limits and 10 healthy controls. Once selected, we used functional magnetic resonance imaging (fMRI) to investigate brain areas involved in PASAT performance in both groups. Results showed that the task activated the left frontal (BA6 and 9) and parietal cortex (BA7 and 40) in both groups, but MS patients showed a stronger activation in the left prefrontal cortex (BA9, 44 and 45) when compared with controls. These results confirmed those obtained post hoc by Audoin et al. [Audoin, B., Ibarrola, D., Ranjeva, J.P., Confort-Gouny, S., Malikova, I., Ali-Chérif, A.M., Pelletier, J., Cozzone, P., et al., 2003. Compensatory cortical activation observed by fMRI during cognitive task at the earliest stage of MS. Hum. Brain Mapp. 20, 51-58], and we interpreted this as showing true cortical reorganization.