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.
Highlights
Motor symptoms are variably expressed in patients with Parkinson’s disease (PD), i.e. patients with identical summary motor scale scores may express large heterogeneity in specific motor subscores
The total UPDRS-III score significantly correlated with the functional responses in the basal ganglia regardless of the treatment condition (‘in’ approach, yellow clusters on Figure 2b), completely suppressed the activity corresponding to treatment contrast (ON-OFF), when used as a nuisance variable (‘out’ approach, no red clusters on Figure 2b)
We revealed the responses to dopaminergic treatment in the basal ganglia, in accordance with previous functional magnetic resonance imaging (fMRI) work from Kraft et al [12], Holiga et al [11] and a positron emission tomography study by Feigin et al [13]
Summary
Motor symptoms are variably expressed in patients with Parkinson’s disease (PD), i.e. patients with identical summary motor scale scores may express large heterogeneity in specific motor subscores. The common practice in functional magnetic resonance imaging (fMRI) studies analysing intra- and inter-individual variability in PD patients is to unify the investigated group by involving subjects with a homogenous, narrow distribution of their demographic and clinical characteristics (e.g. age, gender, disease duration, disease laterality, clinical scores). We considered the variability of PD motor symptoms using the motor part of the Unified Parkinson’s Disease Rating Scale (UPDRS-III) from two different perspectives. In the UPDRS-III ‘in’ approach, the analysis is aimed on revealing potential linear relationships between the particular scores and movement-related brain activity, by detecting the brain regions whose activity correlated with the severity of separate motor symptoms, and further illustrating the general impact of characteristic disease aspects on the fMRI brain responses
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