Objective: Gait dysfunction is one of the most difficult motor signs to treat in patients with Parkinson's disease (PD). Understanding its pathophysiology and developing more effective therapies for parkinsonian gait dysfunction will require preclinical studies that can quantitatively and objectively assess the spatial and temporal features of gait. Design: We developed a novel system for measuring volitional, naturalistic gait patterns in non-human primates, and then applied the approach to characterize the progression of parkinsonian gait dysfunction across a sequence of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatments that allowed for intrasubject comparisons across mild, moderate, and severe stages. Results: Parkinsonian gait dysfunction was characterized across treatment levels by a slower stride speed, increased time in both the stance and swing phase of the stride cycle, and decreased cadence that progressively worsened with overall parkinsonian severity. In contrast, decreased stride length occurred most notably in the moderate to severe parkinsonian state. Conclusion: The results suggest that mild parkinsonism in the primate model of PD starts with temporal gait deficits, whereas spatial gait deficits manifest after reaching a more severe parkinsonian state overall. This study provides important context for preclinical studies in non-human primates studying the neurophysiology of and treatments for parkinsonian gait.
Bibliographical noteFunding Information:
This work was supported by funding from the National Institutes of Health: P50-NS123109, P50-NS098573, R01-NS037019, R01-NS058945, R37-NS077657, R01-NS094206, and R01-NS117822; Minnesota's Discovery, Research and Innovation Economy (MnDRIVE) Brain Conditions Program; Engdahl Family Foundation; and a fellowship for AD (F31-NS108625).
Copyright © 2022 Doyle, Bauer, Hendrix, Yu, Nebeck, Fergus, Krieg, Wilmerding, Blumenfeld, Lecy, Spencer, Luo, Sullivan, Brackman, Ross, Best, Verma, Havel, Wang, Johnson, Vitek and Johnson.
- Parkinson's disease
- non-human primate
- pressure walkway
PubMed: MeSH publication types
- Journal Article