A novel paradigm for modelling freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is a common cause of disability in Parkinson’s disease (PD) but its underlying pathophysiology is poorly understood. A recent hypothesis has proposed that FOG is related to a problem of set-shifting between motor, cognitive and limbic pathways. In this model, the functional convergence of these pathways on the output nuclei of the basal ganglia is believed to result in paroxysmal excessive inhibition of the thalamus and brainstem nuclei leading to freezing episodes. This hypothesis could be assessed with functional neuroimaging but would require a behavioural paradigm capable of modelling FOG. In this experiment, 12 patients with PD underwent assessment on a novel computer-based paradigm where they navigated a realistic three-dimensional environment in which cognitive and limbic load could be manipulated. Performance on this paradigm was significantly correlated with self-reported FOG symptoms assessed by a validated questionnaire. We believe this paradigm is capable of accurately modelling FOG and will have validity in future functional neuroimaging and therapeutic intervention studies.