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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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Parkinson’s disease (PD) is associated with a loss of central dopaminergic pathways in the brain leading to an abnormality of movement, including saccades. In PD, analysis of saccadic latency distributions, rather than mean latencies, can provide much more information about how the neural decision process that precedes movement is affected by disease or medication. Subject to the constraints of intersubject variation and reproducibility, latency distribution may represent an attractive potential biomarker of PD. Here we report two studies that provide information about these parameters, and demonstrate a novel effect of dopamine on saccadic latency, implying that it influences the neural decision process itself. We performed a detailed cross-sectional study of saccadic latency distributions during a simple step task in 22 medicated patients and 27 age-matched controls. This revealed high intersubject variability and an overlap of PD and control distributions. A second study was undertaken on a different population specifically to investigate the effects of dopamine on saccadic latency distributions in 15 PD patients. l-dopa was found to prolong latency, although the magnitude of the effect varied between subjects. The implications of these observations for the use of saccadic latency distributions as a potential biomarker of PD are discussed, as are the effects of l-dopa on neural decision making, where it is postulated to increase the criterion level of evidence required before the decision to move is made. [ABSTRACT FROM AUTHOR]