Resting-state connectivity predicts levodopa-induced dyskinesias in Parkinson's disease

TY - JOUR

T1 - Resting-state connectivity predicts levodopa-induced dyskinesias in Parkinson's disease

AU - Herz, Damian M

AU - Haagensen, Brian N

AU - Nielsen, Silas H

AU - Madsen, Kristoffer H

AU - Løkkegaard, Annemette

AU - Siebner, Hartwig R

N1 - © 2016 International Parkinson and Movement Disorder Society.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connectivity. Methods: Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication.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. Results: 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). Modulation of resting-state connectivity between the supplementary motor area and putamen predicted interindividual differences in dyskinesia severity (R2 = 0.627, P = .004). Resting-state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity. Conclusions: The results corroborate the notion that altered dopaminergic modulation of cortico-striatal connectivity plays a key role in the pathophysiology of dyskinesias in PD.

AB - Background: Levodopa-induced dyskinesias are a common side effect of dopaminergic therapy in PD, but their neural correlates remain poorly understood. Objectives: This study examines whether dyskinesias are associated with abnormal dopaminergic modulation of resting-state cortico-striatal connectivity. Methods: Twelve 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. Results: 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). Modulation of resting-state connectivity between the supplementary motor area and putamen predicted interindividual differences in dyskinesia severity (R2 = 0.627, P = .004). Resting-state connectivity between the right inferior frontal gyrus and putamen neither predicted dyskinesia status nor dyskinesia severity. Conclusions: The results corroborate the notion that altered dopaminergic modulation of cortico-striatal connectivity plays a key role in the pathophysiology of dyskinesias in PD.

KW - Aged

KW - Antiparkinson Agents

KW - Connectome

KW - Dyskinesia, Drug-Induced

KW - Female

KW - Humans

KW - Levodopa

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Parkinson Disease

KW - Prefrontal Cortex

KW - Prognosis

KW - Putamen

KW - Sensorimotor Cortex

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/mds.26540

DO - 10.1002/mds.26540

M3 - Journal article

C2 - 26954295

SN - 0885-3185

VL - 31

SP - 521

EP - 529

JO - Movement Disorders

JF - Movement Disorders

IS - 4

ER -