The neurophysiological deficits that underlie gait impairments in premanifest and manifest Huntington's disease (HD) are not known. By using electroencephalography (EEG) to measure movement related potentials (MRPs) in brain activity during gait initiation, we gained insight into the temporal abnormalities of the basal ganglia (BG)-supplementary motor area (SMA) interaction. This provides a bridge between functional deficits and neuropathology in the progression of HD, and has the potential to both impact clinical practice and inform the development of new non-invasive biomarkers.
Identifying biomarkers, either invasive or non-invasive, remains a critical goal in HD research. Non-invasive biomarkers will allow clinicians to more easily identify pre-manifest and early-stage individuals that are close to the manifestation of symptoms, ultimately optimizing clinical management. MRPs in brain activity during gait initiation have the potential to be one such low-cost non-invasive biomarker in HD. Although disturbances in gait initiation begin in the premanifest stages and continue through disease progression, little is known about the neural mechanisms underlying these disturbances. MRPs can provide direct neurophysiological evidence of malfunction of BG-SMA interaction in gait disturbances, and provide a sensitive and non-invasive biomarker for HD.
Furthermore, MRPs could extend the opportunity to better diagnose movement impairments in people with HD, as well as potential utilization as a marker of intervention effectiveness for exercise and locomotor training studies. A biomarker established through this modality would provide a direct view of the underlying pathophysiology of motor function, and therefore is highly likely to be a sensitive measure of disease progression. Therefore, the task to understand neurophysiological mechanisms that underlie gait impairments in HD remains critical.