Motor Matters: Tackling Heterogeneity of Parkinson’s Disease in Functional MRI Studies

Abstract

To tackle the heterogeneity of Parkinson’s disease symptoms, most functional imaging studies tend to select a uniform group of subjects. We hypothesize that more profound considerations are needed to account for intra/inter-subject clinical variability and possibly for differing pathophysiological processes. Twelve patients were investigated using functional magnetic resonance imaging during visually-guided finger tapping. To account for disease heterogeneity, the motor score and individual symptom scores from the Unified Parkinson’s Disease Rating Scale (UPDRS-III) were utilized in the group-level model using two approaches either as the explanatory variable or as the effect of interest. Employment of the UPDRS-III score and symptom scores was systematically tested on the resulting group response to the levodopa challenge, which further accentuated the diversity of the diseased state of participants. Statistics revealed a bilateral group response to levodopa in the basal ganglia. Interestingly, systematic incorporation of individual motor aspects of the disease in the modelling amended the resulting activity patterns conspicuously, evidencing a manifold amount of explained variability by the particular score. In conclusion, the severity of clinical symptoms expressed in the UPDRS-III scores should be considered in the analysis to attain unbiased statistics, draw reliable conclusions and allow for comparisons between research groups studying Parkinson’s disease using functional magnetic resonance imaging.

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“…The UPDRS-III score and the hemibody, axial, akinesia, rigidity, and tremor subscores were systematically extracted from the UPDRS-III score sheets for more elaborate, symptom-driven fMRI analyses ( Holiga et al, 2013 ) (see the fMRI analyses section ). To assess changes in patients' motor symptoms severity pre- and post-implantation, the UPDRS-III score was evaluated using a repeated measures analysis of variance (rm-ANOVA).…”

“…Additionally, a linear regression group model was fitted to discover potential linear relationships between the EC maps and the particular UPDRS-III scores/sub-score (hemibody, axial, akinesia, rigidity, tremor) ( Holiga et al, 2013 ), but also edema ratings, irrespective of the stage of surgery. A dot-plot was formed to illustrate the linear relationship between adjusted EC response at a specific brain coordinate and the UPDRS-III score for each patient/stage (13 patients × 2 stages).…”

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