Novel functional imaging approaches for investigating brain plasticity in multiple sclerosis and Parkinson’s disease: from research to clinical applications

Neuronal plasticity, as the capacity of the brain to respond to external demands or to injury, has emerged as a crucial mechanism to preserve, at least in part, an adequate behavioral functioning after an injury and as the process underlying improvements in disability during rehabilitation. Brain plasticity can be detected with both structural and functional magnetic resonance imaging and more and more processing techniques have been developed to better capture the occurring changes and to better define the potential plasticity. Gait and balance are affected in patients with multiple sclerosis since the early stages of the disease with sensory deficits playing a major role in determining both balance and gait impairment. Moreover, gait disorders are one of the major causes of disability in patients with Parkinson’s disease, in particular if suffering from freezing of gait. With this work we aimed at i) investigating the functional reorganization occurring in multiple sclerosis at both early and late stages of the disease, ii) characterizing the functional pattern underlying sensory impairment in patients with early multiple sclerosis and iii) verifying the neural correlates of action observation of gait in patients with Parkinson’s disease. These different studies fit into a larger framework where neuroimaging techniques, in particular functional imaging, would support the clinicians in identifying tailored rehabilitation treatments and the patients who would better benefit from them. We found that patients with early multiple sclerosis showed a higher brain functional flexibility, expressed in terms of blood oxygen level dependent signal variability, which correlated to clinical disability, representing a possible compensatory mechanism. In patients with early multiple sclerosis we also observed subtle position sense deficits, not detectable with a standard neurological examination, and which affected still standing balance. Moreover, these deficits were related to a structural damage at the level of the corpus callosum and to functional activity patterns mainly involving the frontoparietal regions. On the contrary, patients with multiple sclerosis at the progressive stages presented with more subtle changes in the resting state functional connectivity which, nonetheless, were related to clinical disability. Lastly, the presence of freezing of gait in patients with Parkinson disease influenced the neural activation underpinning the action observation of walking. Altogether, these results offer an better insight into the pathophysiological mechanisms underlying disability in patients with multiple sclerosis and constitute a groundwork for the enhancement of rehabilitation protocols to improve gait and balance in both multiple sclerosis and Parkinson’s disease, supporting the embracing of new strategies such as sensory integration and action observation training.