Objective: Investigating the role of dopaminergic medication on the neural mechanisms underlying lower limb motor automaticity during fMRI in 23 patients with PD that were measured both on and off dopamine.

Background: Impairments in motor automaticity cause patients with PD to rely on attentional resources during gait¹, resulting in greater motor variability and a higher risk of falls^1-2. Although dopaminergic circuitry is known to play an important role in motor automaticity^1-2, little evidence exists on the neural mechanisms underlying the breakdown of locomotor automaticity in PD^1-2. This impedes clinical management and is in great part due to mobility restrictions that accompany the neuroimaging of gait.

Methods: Participants performed a virtual reality gait paradigm during fMRI by operating foot pedals to navigate a corridor (‘walk’ condition) or watching the screen while a researcher operated the paradigm from outside the scanner (‘watch’ condition). Step time variability during walk was used as a surrogate measure for motor automaticity (where higher variability equates to reduced automaticity).

Results: Patients demonstrated increased step time variability during the “off” state and showed increased BOLD response in the bilateral orbitofrontal cortices (walk>watch). A parametric modulator analysis revealed that patients on medication recruited the cerebellum during periods of increasing variability, whereas patients off medication instead recruited cortical regions implicated in cognitive control. Finally, a main effect of medication was found for functional connectivity within an attentional motor network and a significant condition by medication interaction for functional connectivity was found within the striatum. Furthermore, functional connectivity within the striatum correlated strongly with increasing step time variability during walk in the off state (r=0.616, p=0.002), but not in the on state (r=-0.233, p=0.284). Post-hoc analyses revealed that functional connectivity in the dopamine depleted state within an orbitofrontal-striatal limbic circuit was correlated with worse step time variability (r=0.653, p<0.001).

Conclusions: Overall, this study showed that dopamine ameliorates gait automaticity in Parkinson’s disease by altering striatal, limbic and cerebellar processing, thereby informing future therapeutic avenues for gait and falls prevention.

References:

1. Wu T, Hallett M, Chan P (2015). Motor automaticity in Parkinson’s disease. Neurobiol. Dis. Vol. 82: 226–234.
2. Bohnen NI, Jahn K. Imaging: What can it tell us about parkinsonian gait? Mov Disord. 2013; 28: 1492–1500.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-depletion-impairs-gait-automaticity-by-altering-cortico-striatal-and-cerebellar-processing-in-parkinsons-disease/