Objective: Visual cueing can compensate for impaired automatic gait control in Parkinson’s disease (PD) patients experiencing Freezing of Gait (FOG) by engaging goal-directed motor behaviour¹. Despite its clinical efficacy, the underlying neurophysiological mechanisms remain poorly understood. The CUPID study investigates them using a multi-modal experimental framework that integrates functional magnetic resonance imaging (fMRI), kinematic analyses, and ambulatory electroencephalography (EEG).

Background: Our group has validated a non-immersive Virtual Reality (VR) gait paradigm, in which PD patients navigate a first-person view on a laptop screen by alternating left and right foot pedals^{2, 3}. Performance on that paradigm accurately models FOG, with the percentage time spent frozen (%TF) in the VR environment correlating strongly with the %TF recorded during Timed Up and Go (TUG) tasks³. The VR gait paradigm has also been combined with fMRI to explore FOG triggers^{2, 4, 5}, while ambulatory EEG recordings during TUG has helped identify the brain dynamics of FOG⁶.

Method: CUPID aims to examine a total of 20 freezers, and to date, 5 male PD patients (73.4±5.8 years of age) are included in this preliminary analysis. Participants completed two 5-minute VR gait sessions and two minutes of overground walking, both with and without visual cues, while equipped with 5 inertial measurement units (IMUs)⁷, in both the medication OFF and ON states. Statistical analysis was performed using a two-factorial ANOVA with the factors medication state and condition.

Results: Medication state had a significant effect on modal and median foot step latency in the VR, while condition (uncued vs. cued VR walking) and their interaction did not. Kinematic analysis of overground walking confirmed major medication effects e.g. on cadence, step duration, and gait speed. However, cueing significantly affected circumduction asymmetry and showed an interaction with medication for elevation at mid-swing asymmetry and sagittal range of motion. An additive effect of medication and condition was observed for the Toe Off angle.

Conclusion: These preliminary results demonstrate a primary medication effect detected by both VR and IMUs, with IMUs proving more sensitive than VR measures in capturing cueing effects. Further insights are expected from the analysis of the full cohort, integrating ambulatory EEG and fMRI, and correlating behavioral data from VR with real walking.

References: 1. Ginis P, Nackaerts E, Nieuwboer A, Heremans E. Cueing for people with Parkinson’s disease with freezing of gait: A narrative review of the state-of-the-art and novel perspectives. Ann Phys Rehabil Med 2018;61(6):407-413.
2. Matar E, Shine JM, Naismith SL, Lewis SJ. Using virtual reality to explore the role of conflict resolution and environmental salience in freezing of gait in Parkinson’s disease. Parkinsonism Relat Disord 2013;19(11):937-942.
3. Shine JM, Matar E, Bolitho SJ, et al. Modeling freezing of gait in Parkinson’s disease with a virtual reality paradigm. Gait Posture 2013;38(1):104-108.
4. Gilat M, Shine JM, Walton CC, O’Callaghan C, Hall JM, Lewis SJG. Brain activation underlying turning in Parkinson’s disease patients with and without freezing of gait: a virtual reality fMRI study. NPJ Parkinsons Dis 2015;1:15020.
5. Shine JM, Matar E, Ward PB, et al. Freezing of gait in Parkinson’s disease is associated with functional decoupling between the cognitive control network and the basal ganglia. Brain 2013;136(Pt 12):3671-3681.
6. Cao Z, John AR, Chen HT, et al. Identification of EEG Dynamics During Freezing of Gait and Voluntary Stopping in Patients With Parkinson’s Disease. IEEE Trans Neural Syst Rehabil Eng 2021;29:1774-1783.
7. Mancini M, McKay JL, Cockx H, et al. Technology for measuring freezing of gait: Current state of the art and recommendations. J Parkinsons Dis 2025;15(1):19-40.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/unravelling-the-neural-correlates-of-visual-cueing-in-parkinsons-disease/