Abstract
ABSTRACTBackgroundLevodopa‐induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood.ObjectivesThis study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting‐state cortico‐striatal connectivity.MethodsTwelve PD patients with peak‐of‐dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication. All patients received a single dose of fast‐acting soluble levodopa and then underwent resting‐state functional magnetic resonance imaging before any dyskinesias emerged. Levodopa‐induced modulation of cortico‐striatal resting‐state connectivity was assessed between the putamen and the following 3 cortical regions of interest: supplementary motor area, primary sensorimotor cortex, and right inferior frontal gyrus. These functional connectivity measures were entered into a linear support vector classifier to predict whether an individual patient would develop dyskinesias after levodopa intake. Linear regression analysis was applied to test which connectivity measures would predict dyskinesia severity.ResultsDopaminergic modulation of resting‐state connectivity between the putamen and primary sensorimotor cortex in the most affected hemisphere predicted whether patients would develop dyskinesias with a specificity of 100% and a sensitivity of 91% (P < .0001). Modulation of resting‐state connectivity between the supplementary motor area and putamen predicted interindividual differences in dyskinesia severity (R 2 = 0.627, P = .004). Resting‐state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity.ConclusionsThe results corroborate the notion that altered dopaminergic modulation of cortico‐striatal connectivity plays a key role in the pathophysiology of dyskinesias in PD. © 2016 International Parkinson and Movement Disorder Society
Highlights
Levodopa-induced dyskinesias (LID) are a common and disabling side effect of levodopa treatment of PD
Dopaminergic modulation of resting-state connectivity between the putamen and primary sensorimotor cortex in the most affected hemisphere predicted whether patients would develop dyskinesias with a specificity of 100% and a sensitivity of 91% (P < .0001)
Resting-state connectivity between SM1 and the putamen increased after levodopa intake in No-LID patients, it decreased in LID patients
Summary
Levodopa-induced dyskinesias (LID) are a common and disabling side effect of levodopa treatment of PD. The main risk factors are disease duration, levodopa dose, and age at onset.[1,2] Yet these factors alone cannot predict whether an individual patient will develop LID. Functional magnetic resonance imaging (fMRI) is a widely used method to study disease-related changes in functional connectivity while patients are at rest and without engaging in a specific task.[3,4] In PD, fMRI-based measures of resting-state connectivity can distinguish patients from healthy controls.[5] Movement Disorders, Vol 31, No 4, 2016
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