Identifying the neural correlates of voluntary stopping in people with Parkinson’s disease using a Virtual Reality gait paradigm

Freezing of Gait (FOG) is a disabling feature of Parkinson’s disease (PD). However, the neural mechanisms underlying voluntary stopping impairments remain unclear. This study used a validated Virtual Reality (VR) gait paradigm to investigate the neural correlates of cued voluntary stopping in 15 PD participants with FOG, 10 PD participants without FOG, and 12 healthy controls.

PD participants were assessed on and off dopaminergic medication. Blood-oxygen-level-dependent (BOLD) signals during voluntary stopping were compared with walking and rest periods. In the OFF state, PD participants showed impaired voluntary stopping relative to healthy controls, relying predominantly on the Supplementary Motor Area (SMA).

Dopaminergic medication restored stopping performance to levels comparable to healthy controls and was associated with broader recruitment of occipital, cerebellar, and inferior frontal regions. Freezers exhibited greater stopping deficits and relied on the SMA in both medication states. They also demonstrated reduced functional connectivity across occipital, temporal, and cerebellar regions in the ON state and recruited fewer cortical regions compared to non-freezers, particularly in the OFF state.

The findings suggest that PD participants with FOG fail to engage a disseminated voluntary stopping network. Future work should explore interactions between the stopping network and brainstem gait and balance systems. We thank all participants for their valuable support of our research.

Gülke is currently funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, 522710045). Lewis is funded by the National Health and Medical Research Council Leadership Fellowship (1195830). Parkinson’s Disease Research Clinic, Macquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia Eileen Gülke, Christopher Coppin, John Azizi, Lachlan Churchill, Yanqiu Tian & Simon J.

Lewis Department of Neurology, University Medicine Greifswald, Greifswald, Germany Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Systems Neuroscience, University Medical Center Hamburg- Eppendorf, Hamburg, Germany Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute for Medical Research, Sydney, NSW, Australia E. Gülke has no direct competing interests related to this study. Gülke received speaker honoraria for presentations at symposia sponsored by Zambon/Weser GmbH, Grifols, Kreiskrankenhaus Gummersbach, and Bial.