Change in motor state equilibrium explains prokinetic effect of apomorphine on locomotion in experimental Parkinsonism
Gait impairments remain an unresolved challenge in Parkinson's disease (PD). Clinical studies highlight the importance of neural oscillations underlying motor deficits. Yet, how dopaminergic medication impacts brain activity for gait therapy remains poorly understood. To address this issue, we explored the influence of apomorphine on cortical oscillations during self-initiated locomotion on a runway in the unilateral 6-OHDA rat model of PD. In this task, deficits are characterized by slow movements and repeated interruptions of the gait sequence. Our results show that apomorphine reduced akinesia, increased voluntary transitions to gait, and prolonged individual gait bouts leading to an overall increase in the travel distance on the runway. In contrast, kinematic analysis revealed that these prokinetic changes were accompanied by a reduction in leg velocity and step length. At the neural level, behavioral changes correlated with a shift from beta and low-gamma to high-gamma brain rhythms. Beta and low-gamma significantly correlated with reduced transitions to gait, while high-gamma lead to a shift away from akinesia to prokinetic motor states. Together, our results provide new insights into the cortical regulation of locomotion and reveal the potential of apomorphine to differentially regulate gait sequence execution and gait kinematics. We propose that the prokinetic effects of apomorphine are best explained by the concept of a motor state equilibrium that is defined by the observable motor states, their durations and number of state transitions. This concept provides a simplified representation of complex treatment effects and holds promise to improve data interpretation for clinical translation.