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Abstract:
Previous studies investigating the effect of dopaminergic medication on neural response in Parkinson's disease (PD) using functional magnetic resonance imaging (fMRI) have produced conflicting results. Not accounting for intra-subject asymmetry and inter-subject variability of the disease in the statistical analyses further accentuated by repeated sessions for levodopa intervention might have been a potential source for discrepancy in interpretations of aforementioned studies. We hypothesized that personalizing the fMRI modeling by means of individual movement performance and Unified PD Rating Scale (UPDRS) scores needs to be considered to attain unbiased inferences and reveal the ‘true' response of patients to levodopa.
Twelve right-handed male patients with advanced akinetic-rigid type PD (Hoehn-Yahr stages II-III, age: 45-64 years) were measured during visuo-motor fMRI (a) after overnight withdrawal of levodopa (OFF) and (b) one hour after administration of 250mg of levodopa/25mg carbidopa (ON). Individual-level fMRI models were enhanced with movement performance of participants recorded with MR-compatible sensory gloves. The effect of adding a specific aspect of motor part of the UPDRS scores (UPDRS-III) in the group-level model (ON-OFF) was systematically inspected.
Parametric maps revealed bilateral group response to levodopa in basal ganglia, in accordance with recent studies supporting the normalizing effect of levodopa in putamen in circuits of the current patophysiological model of PD. Interestingly, models incorporating individual movement performance accounting for intra-subject variability provided significantly higher amplitude and extent of activity compared to commonly used generic models. Furhtermore, considering the intra-subject variability by employing particular items of UPDRS-III varied the degree of activity substantially. Akinesia and rigidity subscores described the highest amount of unexplained variability, i.e. equalized the group's clinical picture most appropriately, thus delivered the most sensitive group response to levodopa. We advocate personalizing the statistical evaluations of PD fMRI motor studies and remove the inter/intra-subject variability to draw trustworthy conclusions.
