Virtual reality walking and dopamine: Opening new doorways to understanding freezing of gait in Parkinson's disease

• FOG can be provoked by environmental cues such as passing through doorways.
• Virtual reality environments have been shown to be useful for exploring FOG.
• Dopamine is found to improve motor-associated motor output by doorways in freezers.
• Results implicate dopaminergic pathways in pathology underlying doorway-evoked FOG.
• Combining VR with fMRI may delineate neural correlates of doorway provoked FOG.

Freezing of gait (FOG) is a disabling form of gait disturbance that is common in the advanced stages of Parkinson's disease (PD). Despite its prevalence, methods of studying and assessing FOG are limited. We have previously shown that a virtual reality paradigm was able to distinguish between those who report FOG (“freezers”) and those who do not report FOG (“non-freezers”). In this paradigm, ‘freezers’ were found to have prolonged footstep latency in response to known triggers of FOG including doorways, sliding doors and dual-tasking. In this study, we employed the same paradigm to assess performance of 27 freezers and 14 non-freezers in their clinical ‘on’ and ‘off’ medication states. In this study, only participants in the freezing group demonstrated statistically significant increases in latencies experienced in the ‘off’ state compared to the ‘on’ state in response to wide and narrow doorways and the opening of a sliding door. By contrast, these behavioral differences were not apparent in non-freezers. Furthermore the delay was specific to environmental cues and was not due to generalized slowing in the ‘off’ state. The findings suggest that this motor delay when processing environmentally salient cues is specific to freezers and is partially mediated by dopamine-dependent neurocircuitry.