New paradigms are developed in magnetic resonance imaging for the advanced diagnosis of neurodegenerative diseases. In particular, multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) preclinical research poorly focuses on functional connectivity in brain. Available animal models of MS and ALS are extensively used for analysis such drug testing and discovery of underlying mechanisms of pathogenesis. These diseases present, since neuronal lesions formation and neuroinflammation, a multilevel heterogeneity in mechanism of neurodegeneration and brain connectivity still not well understood. Moreover, they play a key role in pharmacological research, from the identification of a therapy target to the in vivo validation of the efficacy. More recently alterations in synchronized brain activity at rest in MS patients have been reported. At the best of our knowledge, functional imaging has not been applied yet in the assessment of new therapies in the preclinical models for MS and ALS. In this study, we aim to develop an innovative platform based on functional MRI in the resting state (rsfMRI), for the pre-clinical evaluation of new markers in MS and ALS. Moreover, the advancing in MRI techniques could assess new criteria of sensitivity and specificity in diagnosis; an additional analysis on diffusion MRI outcomes in MS preclinical models is added to this study