Present and future of fMRI in multiple sclerosis.

Studies with functional MRI (fMRI) of the motor, visual and cognitive networks have consistently demonstrated functional cortical changes in the major multiple sclerosis (MS) clinical phenotypes. Compared with healthy subjects, these fMRI modifications are characterized by an altered recruitment of regions normally devoted to the performance of a given task, recruitment of additional areas, different resting state activity and disrupted connectivity. Studies that applied fMRI longitudinally have shown that such abnormalities vary over the course of the disease, not only after an acute relapse but also in clinically stable patients. fMRI and structural MRI abnormalities of the MS brain are correlated. Movement- and cognitive-associated fMRI changes were found to correlate with the amount of damage to brain normal-appearing white and gray matter and to the spinal cord. This suggests that, at least in some phases of the disease, increased recruitment of 'critical' central nervous system regions might contribute to limiting the functional impact of MS-related injury. fMRI has recently been applied to the assessment of functional modifications in the cervical cord of patients with MS. Evidence to date shows that cervical cord fMRI can reliably identify regions involved with tactile and proprioceptive stimulation in MS patients and different clinical phenotypes. As shown in brain studies, these investigations have detected increased recruitment in MS patients compared with healthy controls. At present, fMRI is a useful research tool, and reliable analysis and display methods have been developed. Future perspectives include development of fMRI paradigms for patients with MS-related disability and application of this technique in longitudinal studies to define the temporal evolution of functional cortical changes in different MS phenotypes as well as the effects of various therapeutic approaches on central nervous system plasticity.