Studies with conventional magnetic resonance imaging (MRI) indicate that cognitive impairment in multiple sclerosis (MS) patients is not fully explained by the burden of T2-visible lesions in the brain. Other non-conventional MRI techniques with increased specificity to the more destructive aspects of MS pathology, such as magnetization transfer MRI, diffusion-weighted MRI and proton magnetic resonance spectroscopy, have recently been applied to MS cognitive studies. The results suggest that the presence and extent of "occult" MS pathological features in the normal-appearing brain tissue and the location of lesions in eloquent sites play a central role in the pathogenesis of MS neuropsychological impairment.