Biomechanical and Neural Factors Associated with Gait Dysfunction and Freezing in People with Parkinson Disease

Parkinson disease: PD) is a progressive neurological disorder with no known cure, affecting one million Americans. Half of those with PD experience freezing of gait: FOG), manifested as an inability to complete effective stepping. Gait dysfunction and FOG are associated with falls, severe injury, and reduced quality of life, and are among the most disabling and distressing symptoms of PD. The causes of FOG and gait dysfunction are not well understood. Further, FOG is notoriously difficult to elicit in a laboratory setting, making efforts to track or identify individuals at risk for freezing difficult. An important first step in determining the mechanism of gait dysfunction and FOG is to identify factors associated with these symptoms. Therefore, the overall goal of this project was to better understand how pathologies of movement and brain function are associated with gait dysfunction and FOG. To this end we conducted three experiments: chapters 2-4). In experiment 1: chapter 2), we assessed the relationship between coordination of steps and freezing of gait. Results suggested that individuals with PD who freeze exhibit worse coordination than those who do not freeze, and further, that tasks related to freezing: turning and backward walking) resulted in worse coordination than forward walking. Finally, there was a significant positive correlation between freezing severity and global coordination of steps. These results together support the hypothesized relationship between coordination of steps and freezing. In experiment 2: chapter 3), we investigated neural signals associated with gait dysfunction: measured via blood oxygen level dependent [BOLD] signal) in those with PD compared to healthy adults. We found that during complex gait tasks, those with PD activated the supplementary motor area more than healthy adults. In addition, we observed reduced activity in the globus pallidus in people with PD. Finally, PD exhibited consistent positive correlations between a measure of gait function: overground walking velocity) and brain activation such that those with higher brain activity exhibited better gait function. In experiment 3: chapter 4), we investigated the neural underpinnings of freezing of gait. Specifically, we looked at gait imagery in those with PD who do experience freezing: freezers) and those who do not: non-freezers). We found those who experience freezing exhibited reduced BOLD signal in the cerebellar locomotor region, suggesting dysfunctional activity in this region may play a role in freezing. BOLD response within freezer and non-freezer groups were not consistently correlated to functional gait measures such as overground gait speed or freezing severity. Together these results better elucidate how pathologies of movement: i.e. coordination of steps) and neural function are related to gait dysfunction and freezing. Specifically, we found that coordination of steps and activity of the cerebellar locomotor regions may be related to freezing. Further, altered activation of the globus pallidus may be related to gait dysfunction in those with PD, and generally, larger BOLD response is correlated to improved overground gait function