Dopaminergic modulation of timing control and variability in the gait of Parkinson's disease

Abstract

The basal ganglia have been implicated in timing control, yet the nature of timing disturbances in Parkinson's disease (PD) is poorly understood. We evaluated the influence of timing cues on spatiotemporal aspects of gait control and its variability, and the impact of dopaminergic treatment on timing. Three separate groups: 19 PD (OFF state); 24 PD (ON state); and 30 control participants were tested. Participants walked on a computerized carpet at four randomized and metronome-controlled rates: self-paced, 60, 80, or 100 steps/min. To our knowledge, this is the first study to demonstrate that medicated PD patients had poorer timing control than patients withdrawn from medication and healthy participants when modulating timing to an external stimulus. Increased step-to-step timing variability and deficits in mean temporal gait characteristics revealed that the medicated PD group (in contrast to nonmedicated PD group) performed least like healthy participants. This was observable in externally-cued conditions, but not during self-paced gait. Similar to previous research, step length contributed to overall slowness in PD, while temporal characteristics of gait did not. Interestingly, healthy participants increased stride length with each increase in cue rate, whereas both PD groups locked their step length regardless of temporal demand. Step-to-step variability differences between PD and healthy (e.g. step and double-support time measurements) may be indicative of specific basal ganglia involvement in temporal control of gait.