Striatal Dopamine Denervation Impairs Gait Automaticity in Drug‐Naïve Parkinson's Disease Patients

Abstract

BackgroundGait automaticity, which is impaired in patients with Parkinson's disease (PD), can be quantified by gait variability analysis. Among the 3 regions of the striatum (sensorimotor, executive, and limbic), the sensorimotor region may play a crucial role in motor automaticity in healthy individuals. However, neural correlates of impaired gait automaticity are poorly investigated in PD.ObjectiveWe aimed to examine the relationship between gait automaticity and striatal dopaminergic depletion in drug‐naïve PD patients.MethodsA total of 21 drug‐naïve PD patients and 12 healthy controls were enrolled. Gait parameters were measured via wearable inertial sensors under fast‐paced gait or cognitive dual‐task conditions, and their respective coefficient of variation (CV) and dual‐task cost were calculated. The extent of striatal dopaminergic depletion was evaluated by dopamine transporter (DAT) imaging with single‐photon emission computed tomography using N‐ω‐fluoropropyl‐2β‐carbomethoxy‐3β‐(4‐[123I]iodophenyl)nortropane. Correlation between DAT uptake and gait variables was analyzed using the region‐of‐interest analysis for the 3 right or left striatal regions and voxel‐based analysis.ResultsPD had higher mean bilateral CV and dual‐task cost of stride length than healthy controls. The mean bilateral CV of stride length was negatively correlated with DAT uptake in the bilateral executive regions of the striatum. Voxel‐based analysis revealed a negative correlation between the mean bilateral CV of stride length and DAT uptake in the anteromedial striatum.ConclusionsDopaminergic denervation in the anteromedial striatum, a part of the executive region, is associated with impaired gait automaticity in drug‐naïve PD patients. This region may compensate for the posterior sensorimotor striatum, maintaining gait automaticity. © 2020 International Parkinson and Movement Disorder Society

The Adapted Resistance Training with Instability Randomized Controlled Trial for Gait Automaticity

“…3C). A possible explanation may be that dopaminergic pathways 61 regulate speed, but dopaminergic pathways may not regulate stride length because DTC on stride length is not associated with dopaminergic denervation 17 . Thus, improvement in DTC on stride length may be cholinergic dependent.…”

“…A possible explanation may be that dopaminergic pathways 61 regulate speed, but dopaminergic pathways may not regulate stride length because DTC on stride length is not associated with dopaminergic denervation. 17 Thus, improvement in DTC on stride length may be cholinergic dependent. As the cerebellum receives cholinergic inputs from the brainstem locomotor center 20 and cholinergic dysfunction contributes to reduced stride length 18 and FOG, 19 only changes in DTC on stride length were associated with changes in CLR activation.…”

“…These findings suggest that freezers may fail to adequately recruit cerebellar networks, as the cerebellum plays a role in maintaining locomotor automaticity, 7,14,15 even when freezers are assessed in on state of medication 16 . Although dopaminergic medication improves gait automaticity (ie, lower variability of step time) in freezers and nonfreezers, 16 DTC on stride length is not associated with dopaminergic denervation 17 . Cholinergic dysfunction contributes to reduced stride length 18 and gait speed 18 and increases FOG severity 19 .…”

“…16 Although dopaminergic medication improves gait automaticity (ie, lower variability of step time) in freezers and nonfreezers, 16 DTC on stride length is not associated with dopaminergic denervation. 17 Cholinergic dysfunction contributes to reduced stride length 18 and gait speed 18 and increases FOG severity. 19 As the cerebellum receives cholinergic inputs from the brainstem locomotor center, 20 the cerebellum likely plays important roles in gait automaticity in freezers.…”

Efeitos dos treinamentos multimodal e mat Pilates na marcha e equilíbrio de pessoas com doença de Parkinson: um ensaio clínico randomizado unicego

“…Para manter a habilidade motora, a prática é essencial para transformar este processo em automação e refinar a habilidade, alcançando a marcha eficiente/funcional, que exige menor gasto energético e pouca variabilidade (HIRATA et al, 2020;VANSWEARINGEN;STUDENSKI, 2014).…”