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Freezing of gait is a challenging sign of Parkinson's disease associated with disease severity and progression and involving the mesencephalic locomotor region. No predictive factor of freezing has been reported so far. The primary objective of this study was to identify predictors of freezing occurrence at 5 years. In addition, we tested whether functional connectivity of the mesencephalic locomotor region could explain the oculomotor factors at baseline that were predictive of freezing onset. We performed a prospective study investigating markers (parkinsonian signs, cognitive status and oculomotor recordings, with a particular focus on the antisaccade latencies) of disease progression at baseline and at 5 years. We identified two groups of patients defined by the onset of freezing at 5 years of follow-up; the 'Freezer' group was defined by the onset of freezing in the ON medication condition during follow-up (n = 17), while the 'non-Freezer' group did not (n = 8). Whole brain resting-state functional MRI was recorded at baseline to determine how antisaccade latencies were associated with connectivity of the mesencephalic locomotor region networks in patients compared to 25 age-matched healthy volunteers. Results showed that, at baseline and compared to the non-Freezer group, the Freezer group had equivalent motor or cognitive signs, but increased antisaccade latencies (P = 0.008). The 5-year course of freezing of gait was correlated with worsening antisaccade latencies (P = 0.0007). Baseline antisaccade latencies was also predictive of the freezing onset (χ2 = 0.008). Resting state connectivity of mesencephalic locomotor region networks correlated with (i) antisaccade latency differently in patients and healthy volunteers at baseline; and (ii) the further increase of antisaccade latency at 5 years. We concluded that antisaccade latency is a predictive marker of the 5-year onset of freezing of gait. Our study suggests that functional networks associated with gait and gaze control are concurrently altered during the course of the disease., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Several experiments have shown that smooth pursuit and saccades interact while tracking an object moving across the visual scene. It was proposed two decades ago that the amplitude of saccades triggered during smooth pursuit ('catch-up saccades') were corrected by a delayed sensory signal to account for the ongoing target displacement during catch-up saccades. However, recent studies used targets with non-constant velocity profiles and suggested that the correction of catch-up saccade amplitude must be done through an internal model of target motion. It is widely accepted that an internal model of target motion is also used by the central nervous system (CNS) to cancel inherent delays between visual input and smooth pursuit motor output, ensuring accurate tracking of moving targets. Our study proposes a new paradigm in which the target switches unexpectedly from one target with a non-constant periodic velocity profile to another with a non-constant aperiodic velocity profile. Our results confirm the hypothesis that the CNS uses an internal model of target motion to correct catch-up saccade amplitude. In addition, we reconcile the sensory delayed and the internal model of target motion hypotheses and show that a common internal model of target motion is shared within the CNS to control smooth pursuit and to correct catch-up saccade amplitude. [ABSTRACT FROM AUTHOR]