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

Y1 - 2016/4

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connectivity.METHODS: Twelve PD patients with peak-of-dose dyskinesias and 12 patients without dyskinesias were withdrawn from dopaminergic medication.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 (R(2) = 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 (R(2) = 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

VL - 31

SP - 521

EP - 529

JO - Movement Disorders

JF - Movement Disorders

SN - 0885-3185

IS - 4

ER -