Objective: To study the neural activity related to real-time walking in people with Parkinson’s (PwP) using a novel [¹⁸F]fluorodeoxyglucose (FDG)-Positron Emission Tomography (PET) protocol and compare to older adults.

Background: Impaired mobility is one of the most debilitating and treatment-resistant features of Parkinson’s. The neural control of gait involves a distributed locomotor network spanning cortical, subcortical and brainstem structures. It remains unclear which components of this network contribute to gait impairments in PwP representing a major barrier to therapeutic innovation. Advanced methodology to study the neural control of gait is needed.

Method: Nineteen PwP (67.3±5.6y, 13m) with mild-moderate PD were recruited. Fifteen older adults (65.7±3.9y, 5m) were available.¹ Participants underwent FDG-PET/MR brain imaging following two tasks in a single session: 15-minutes standing and 15-minutes walking, each preceded by an intravenous injection of FDG. To eliminate signal from the first injection (PET_STAND) in the second scan (PET_WALK), we applied a novel ‘dose-correction’.¹ Per-participant contrast images were computed by subtracting the PET scans. Whole brain statistical analyses compared glucose consumption between groups, correcting for multiple comparisons.

Results: Within PwP, the walking—standing comparison elicited significant metabolic increases in a distributed brain network encompassing frontal, sensorimotor, parietal, and visual regions cortically, and cerebellar and thalamic regions subcortically. This is in line with previous findings^2,3. The novelty of our study is the comparison of neural activation patterns during real-time walking between groups. This showed that PwP exhibit hypometabolism in the left caudate in addition to areas important for cognitive control (orbitofrontal cortex), visual motion perception (temporal gyrus) and processing (cuneus, angular and fusiform gyri), and the integration of vestibular signals (posterior insula).

Conclusion: PD-specific impairment in neural activity during real-time gait were identified. Our findings suggest that the neural control of gait in PwP is not characterised by the absence of locomotor network engagement, rather by reduced task-dependent up-regulation of distributed sensory-associative networks required for adaptive gait. These insights offer a foundation for developing interventions to improve mobility, empowering PwP to maintain independence for longer.

References: [1] Sigurdsson, et al. 2024 PMID: 38331333.
[2] Hanakawa, et al. 1999 PMID: 10388793
[3] Pellegrini, et al. 2023 PMID: 39186320

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neural-control-of-real-time-walking-in-people-with-parkinsons-disease/