Brain activity response to cues during gait in Parkinson’s disease: A study protocol


Various cueing strategies (internal and external) have been used to alleviate gait deficits in Parkinson’s disease (PD). However, it remains unclear which type of cueing strategy is most effective at different disease stages or with more severe walking impairment, such as freezing of gait (FOG). The underlying neural mechanisms of response to cueing are also unknown. This trial aims to: (i) determine brain activity response to cue stimulus (internal, visual, auditory or tactile) when walking in PD and; (ii) examine changes in brain activity to cues at different stages of PD. This ongoing single-site study uses an exploratory observational design, with laboratory application of cues for gait deficit. A total of 80 people with PD who meet the inclusion criteria will be enrolled. Participants are split into groups dependent on their disease stage (classified with the Hoehn and Yahr (H&Y) scale); n = 20 H&YI; n = 30 H&YII; n = 30 H&YIII. Within the H&Y stage II and III groups, we will also ensure recruitment of a sub-group of 15 individuals with FOG within each group. Participants perform walking tasks under several conditions: baseline walking without cues; randomized cued walking conditions [internal and external (visual, auditory and tactile) cues]. A combined functional near-infrared spectroscopy and electroencephalography system quantifies cortical brain activity while walking. Inertial sensors are used to assess gait. Primary outcome measures are cue-related changes in cortical brain activity while walking, including the relative change in cortical HbO 2 and the power spectral densities at alpha (8-13Hz), beta (13-30Hz), delta (0.5-4Hz), theta (4-8Hz) and gamma (30-40Hz) frequency bandwidths. Secondary outcome measures are cue-related changes in spatiotemporal gait characteristics. Findings will enhance our understanding about the cortical responses to different cueing strategies and how they are influenced by PD progression and FOG status. This trial is registered at (NCT04863560; April 28, 2021,