Objective: To establish the contribution of striatal dopamine to gait initiation in Parkinson’s disease.

Background: Gait initiation (GI) is characterized by anticipatory postural adjustments (APAs), a feedforward motor program centrally activated. Feedforward control does not rely on an external feedback and requires internal models (predictive mechanisms) to execute a motor command.

Method: We recruited 26 subjects with PD (18M, age: 61±8 yr, disease duration: 11±5 yr, UPDRS-III score: 29±10 after overnight suspension of all dopaminergic drugs [meds-off] and 10±5 at 60 min after oral intake of 200/50 mg of levodopa/benserazide [meds-on (n=13)]). We also enrolled 27 age- and gender-matched healthy controls (HC, 17M, age: 61±5 yr). APAs were described by kinematic (Smart DX, BTS) and dynamic (Kistler force plates) measurements. All patients also performed a single-photon computed tomography (SPECT) with FP-CIT, a ligand binding selectively to the dopamine reuptake transporters (DAT). The key features of the Centre of Pressure (CoP) pathway and the Centre of Mass during APAs were characterized using ad hoc Matlab algorithms. Differences between groups were analyzed with Steel-Dwass all pairs or Wilcoxon matched pairs (a pair being a subject in meds-off and -on condition) and a multivariate correlation analysis (Spearman’s ρ). FP-CIT uptake values were calculated with the Basal Ganglia Matching Tool.

Results: The most relevant finding was a significant correlation between the antero-posterior displacement of the CoP during the imbalance phase (characterized by initial displacement of the CoP backward and toward the future leading foot) and DAT binding values of the contralateral putamen (ρ=0.48, p<0.05). This measurement significantly differed between PD and HC (27±16 and 37±15 mm respectively, p<0.05) and improved after levodopa intake (35±27% average increase, p<0.01).

Conclusion: Our results suggest a selective involvement of striatal dopamine in coding the spatial properties of APAs during GI. We advance the hypothesis that dopamine modulates the output of the basal ganglia motor control system contributing to the change in body spatial coordination properties (from upright posture during stance to bipedal locomotion).

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-contribution-of-striatal-dopamine-to-feedforward-motor-control-during-gait-initiation-in-parkinsons-disease/