Alby Richard, MD, PhD

, Samuel Frank, MD

Oculomotor Learning as a Biomarker in Huntingt on’s Disease (HD) patients

Despite the well-established genetic cause of Huntington’s Disease (HD), the mechanisms contributing to the progressive motor dysfunction in HD are not fully understood. In the current era of novel treatments for HD, there is a great need for a rapid and relatively non-invasive approach to track disease progression and response to treatment. The differences in motor control between pre-symptomatic individuals and non-HD controls are often subtle, and motor learning tasks offer a promising way to identify these early.

Learning a new motor action or skill requires that the musculoskeletal system gain and perfect novel movements with repeated practice (e.g., learning to play tennis). Any such action requires the coordinated activity of a number of muscles and joints, along with sensory feedback to produce the finely tuned movements leading to the desired behaviour. Previous studies of motor learning using reaching movements have revealed that HD patients are more jittery than age-matched controls, and that it takes longer to learn and consolidate a new movement sequence.

Arm movements are difficult to study as a sensitive marker of disease onset and progression however, since many factors can impact task performance and bias the results (e.g., involuntary movements, which are common in HD). By contrast, eye movements are among the best studied and understood examples of motor control in biology, and can be measured with ease and accuracy using non-invasive eye-tracking techniques. Moreover, eye movement experiments in HD have the benefit (compared to limb movement paradigms) of being less susceptible to artefact and noise from involuntary movements.

Oculomotor learning task performance in HD patients could thus potentially act as a biomarker for different disease stages, while providing new insight into the neurocircuitry of motor learning. The identified circuits may serve as targets for non-invasive neuromodulation as part of a rehabilitative strategy.