UNITE-PD: Unraveling the Neural Mechanisms underlying Compensation Strategies for Gait Impairments in Parkinson*s Disease: a Transnational, Multimodal Approach

Gait impairments are common in Parkinson*s disease (PD) and significantly
impact mobility, independence and quality of life. The application of
compensation strategies - such as external or internal cueing - is an essential
and evidence-based element of gait rehabilitation in PD. Cueing can be highly
effective in improving mobility, but not every patient benefits equally from
the same cueing strategy. A one-size-fits-all approach to gait rehabilitation
therefore does not suffice. At present, the underlying working mechanisms of
cueing strategies are poorly understood, and it is unknown how the efficacy of
different modes of cueing changes longitudinally. Improving the understanding
of the key mechanisms underlying compensation at the neurological systems level
will help to refine cueing strategies and their timely delivery for a hallmark
impairment in PD.

This study aims to achieve 4 goals: (1) to identify the brain network involved
in mediating the effects of cueing as an important compensation strategy; (2)
to identify differences in brain connectivity patterns elicited by internal
versus external cueing, so as to identify shared and dissimilar neural
circuitries; (3) to compare brain connectivity patterns between patients who
benefit from cues versus those who do not, to identify the key effective
components of the compensatory networks in the brain; and (4) to identify the
temporal network changes elicited by long-term use of cueing in order to
ascertain how adaptation to cueing manifests in the brain.

This study is a case-control study with a six month follow-up period.

At baseline, the efficacy of both external and internal cueing strategies will
be determined. Responders will be instructed to apply the effective cueing
strategies in daily life as much as possible when needed during the follow-up
period of six months. Furthermore, they will use an application that runs on a
smartphone that presents a rhythmic auditory stimulus, and records actual use
during gait.

Benefit: We expect responders to potentially benefit from either the external
or internal cueing strategies, which may result in improved gait control and
reduced fall risk.

Burden: Subjects are invited to complete at least one baseline visit to our
laboratory, lasting approximately four hours. If a subject is a responder or
non-responder to cueing, she/he will revisit the laboratory shortly after the
baseline visit and after approximately six months, both lasting approximately
four hours.

Risks: Patients with PD and gait impairments are generally exposed to an
increased risk of falls compared to age-matched controls. Based on previous
literature on compensation strategy or *cueing* training, we do not expect
participation in this study to aggravate the risk of falls. Therefore, we do
not expect potential issues of concern within this study.