It is well known that exercise improves motor and cognitive symptoms in patients with Parkinson's disease (PD), suggesting that exercise may slow down disease progression. However, the mechanisms of such beneficial effects remain elusive. Circumstantial evidence suggests that exercise may increase plasticity-related processes and may counteract neurodegeneration mechanisms. Therefore, our working hypothesis is that a program of intensive and repeated exercise, which is known to induce behavioral improvements in PD, may promote plastic changes both at functional and structural levels in the cortex and in the spinal cord. In particular, we expect improvements in memory formation and sleep quality that are impaired in Parkinson's disease. We also postulate that restored plasticity will induce changes in the sleep architecture.

The project will be articulated in three aims:

Aim 1: We will test the effects of intensive exercise on functional and structural cortical plasticity.

Aim 2: We will test if intensive exercise may also impact spinal cord circuits by looking at muscle synergies and spatiotemporal organization of the spinal motoneuronal output during gait and reaching movements.

Aim 3: We will study post-exercise changes of the sleep pattern, as sleep plays a crucial role in the definition of plasticity-related phenomena. Considering that sleep is important in memory formation, we expect that the increase of plasticity and sleep may improve skill acquisition and retention in PD.

The present project relates specifically to Focus Area FY18 PRP Investigator-Initiated Research as part of the Parkinson's Research Program 2018. The results of these studies will be crucial to determine the mechanisms underlying the beneficial effects of a well-established rehabilitation program for patients with Parkinson. A better comprehension of the mechanism of action of exercise on cortical and spinal plasticity at the system level in humans will be useful to empower rehabilitation tools to slow down disease progression and disability. We do believe that this project will generate, in the next 3 years, breakthrough data on the mechanisms of exercise, novel biomarkers to monitor efficacy of treatments, thus leading to better restorative, disease-modifying, and symptomatic therapies for PD.