Virtual visual cues to reduce freezing in Parkinson*s disease: an explorative study

Freezing of gait (FOG) is a particularly disturbing and potentially harmful
symptom occurring in a majority of people with Parkinson*s Disease (PD) over
the course of disease. External cues, such as a metronome or bars on the floor,
aid in timing and scaling of automatized movement, thereby facilitating
initiation and continuation of gait. The mechanism behind visually cued
movement has not been fully elucidated. The cerebellar-thalamo-cortical (CTC)
network is likely involved in synchronizing movement with an external rhythm,
but has not been studied in patients with PD and FOG (PD-FOG). In this study,
we aim to validate a paradigm to be used in future neuroimaging studies
investigating the neuronal networks underlying visually cued movement. In
addition, this behavioural experiment explores whether moving visual cues in a
virtual reality (VR) environment can improve motor timing and reduce freezing
in persons with PD-FOG.

The main objective of this study is to validate a VR foot pedalling paradigm to
study visual cueing and freezing of gait in patients with PD-FOG, to allow for
its use in future neuroimaging studies. The secondary objective is to assess
the influence of virtual visual cues on freezing and motor timing ability in
persons with PD and FOG.

This is an exploratory behavioral study. Experiments are conducted during a
single visit to the University of Twente while patients are in their
dopaminergic OFF-state (>12 hours after last dopaminergic medication intake).
The study visit consists of reception and explanation about the study (15
minutes), overground walking (42 minutes), VR foot pedalling experiment (33
minutes), questionnaires (45 minutes), and an exit interview (15 minutes),
totaling to about 2.5 hours in a single visit. During the overground walking
test, participants walk along a corridor and are signaled to stop and resume
walking in the presence and absence of equally spaced bars on the floor. To
increase cognitive load and thereby increase the likelihood of eliciting FOG,
the start and stop signals are given as an adjusted auditory Stroop task.
During the VR foot pedalling experiment, participants press foot pedals to
navigate through a virtual reality (VR) environment. Three different conditions
(without visual cues, with transverse bars, and with a staircase displayed in
the VR environment) are repeated 12 times per condition, with rests in between
blocks. Again, the adjusted auditory Stroop task is applied to increase
cognitive load and induce freezing. The questionnaires are used to describe the
demographics of the participants. In the exit interview, participants are asked
for their feedback on their experience with the VR foot pedalling paradigm.
This information is used both to strengthen the interpretation of current
results, and to improve future study set-ups with a similar paradigm.

Participants perform two tasks in a single visit: an overground walking test
and a virtual reality (VR) foot pedalling experiment.

During the overground walking test, participants walk along a corridor and are
signaled to stop and resume walking in the presence and absence of equally
spaced bars on the floor.

During the VR foot pedalling experiment, participants press foot pedals to
navigate through a virtual reality (VR) environment. Three different conditions
(without visual cues, with transverse bars, and with a staircase displayed in
the VR environment) are repeated 12 times per condition, with rests in between
blocks.

All procedures are non-invasive. Experiments are conducted while participants
are in their *OFF* state (>12 hours after last intake of dopaminergic
medication). This is expected to cause more FOG (increasing the power of the
study, requiring less participants) and an increase of PD symptoms which will
resolve upon medication intake after the experiments. Studies in the *OFF*
state are common in PD research and do not pose a risk to participants.
Physical tiredness which might occur during the overground walking test is
minimalized by allowing participants to rest as often and long as needed.
Persons with PD, and especially those with FOG, are, due to the nature of their
disease, at risk for falling. To reduce this risk of falling, a researcher will
continuously accompany the participant during walking. The VR foot pedalling
experiment is performed lying supine, only requiring foot movements. There are
no risks associated with the VR experiment and the burden is considered low.
The questionnaires are widely used in medical research and are considered to
place little burden on the participants.