Title: Neurophysiological correlates of gait initiation in individuals with Huntington’s and Parkinson’s disease
Description: Background: Huntington’s disease (HD) and Parkinson’s disease (PD) are neurodegenerative diseases causing dysfunction and death of cells within the basal ganglia, and thus disruption of pathways with resultant impairment of cognition, motor function, and behavior. These impairments result in decreasing independence in activities of daily living and quality of life even from relatively early in the disease. Among the many motor deficits in HD and PD, impaired gait initiation is a cardinal motor characteristic in both diseases. However, the neurophysiological deficits that underlie gait impairments in people with HD and PD are not well understood. Movement related potentials derived from EEG may insight into the dynamics of areas of the brain involved in motor planning in people with HD and PD. Findings from this study provide a bridge between functional deficits and neuropathology in the progression of HD and has the potential to impact mechanistic understanding of gait initiation in basal ganglia disorders, and inform the development of clinical outcome measures and potential non-invasive biomarkers.

The aims of this study were to: 1) identify the differences in movement-related potentials in individuals with manifest HD and mid-stage PD, and non-neurological peers, 2) verify kinetic differences in gait initiation reflective of postural stability in HD and PD, 3) determine force modulation impairments during gait initiation in the mediolateral (ML) and anteroposterior (AP) direction in HD and PD, and 4) determine the tolerance of a high repetition gait initiation protocol. Methods: EEG data were collected for participants for 5 blocks of 15 trials of gait initiation. Kinetic data was collected using an embedded force plate. EEG was time-locked with kinetic data in real-time. RPs amplitudes and latencies, and CNV amplitudes and latencies were determined prior to the onset of the first APA and heel-off. Center of pressure (COP) displacement averages and excursions were determined in the mediolateral (ML) and anteroposterior (AP) direction as measures of postural stability. COP accelerations and coefficient of variance (COV) of force were derived from gait initiation windows in the ML and AP direction as measures of force modulation.

Tolerability of the protocol was determined by assessing fatigue from changes in COP averages and excursions from the first block of gait as compared to the last block of gait. Mean values, standard deviations, and mean differences between HD and PD were determined for individual and group data. Results: Three individuals with HD and three with PD were recruited with mean ages of 52.67 and 74.3 respectively. Mean differences and effect sizes indicated that HD participants had a greater average COP in the x direction and greater COP max excursions in the y direction relative to PD participants. PD displayed greater COP max excursions in the y direction relative to HD. There were no differences among COP max measures in the x direction. Similarly, there were no differences between HD and PD participants for CNV amplitudes and latencies, and RP amplitudes and latencies prior to APA onset and heel-off. Among impulse values, there were no differences in ML APA impulse between HD and PD participants, however PD participants exhibited a larger impulse in the AP APA.

Lastly, participants were able to tolerate the high repetition protocol as indicated by COP values over three blocks of trials. Discussion: Results confirmed previous findings for kinetic parameters and validated the methodology in its ability to measure movement-related potentials prior to gait initiation in people with HD and PD. No study to date has used wireless EEG technology to measure neural signal in real-time during gait initiation in PD and HD. The values obtained from this system and methods were similar to the results determined in wired and tethered systems. The MRP amplitudes present in the PD participants, along with latencies of MRPs between HD and PD, may indicate potential specificity of MRP responses according to disease-stage and medication-state. Future work will explore the use of MRPs in larger cross-sectional studies and for the development of a meaningful clinical outcome measure.