Rewiring movement in Parkinson's disease: exercise, neuromodulation, and motor control - bridging neuroplasticity, gait biomechanics, and fatigue management for advanced rehabilitation

This doctoral thesis investigates the effects of physical exercise and combined motor–cognitive interventions on motor, neuromuscular, and neuroplastic outcomes in individuals with Parkinson’s disease (PD), adopting a multi-level and mechanism-informed perspective. The work integrates evidence from systematic reviews, an umbrella review, and an experimental study to examine how exercise characteristics and task demands influence functional performance and underlying neural mechanisms in PD. First, a systematic review and meta-analysis examined changes in brain-derived neurotrophic factor (BDNF) following different exercise protocols in PD, showing that higher exercise intensity is positively associated with increases in BDNF levels, supporting a potential role of exercise-induced neuroplasticity. Second, a systematic review on dual-task walking highlighted consistent biomechanical gait alterations in PD, including reduced stride length, gait speed, and increased variability, accompanied by compensatory prefrontal cortex activation, indicating a shift from automatic to cognitively controlled locomotion. Third, an experimental randomized controlled study explored baseline neuromuscular and corticospinal function of the upper limb in early-stage PD, revealing preserved muscle structure and corticospinal excitability, with functional asymmetries suggesting central, rather than structural, mechanisms underlying motor impairment. Finally, an umbrella review of systematic reviews synthesized the broader effects of physical exercise in PD, demonstrating that fitness-oriented exercise produces global motor and physical benefits, while motor–cognitive training more effectively targets balance and dual-task gait deficits; combined interventions may further potentiate neuroplastic adaptations. Overall, the findings support a shift toward targeted, mechanism-based exercise prescription in PD, emphasizing the role of exercise intensity, task complexity, and combined approaches to optimize motor function, cognitive–motor integration, and neuroplastic potential.