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The acute brain response to levodopa heralds dyskinesias in Parkinson disease
Author(s) -
Herz Damian M.,
Haagensen Brian N.,
Christensen Mark S.,
Madsen Kristoffer H.,
Rowe James B.,
Løkkegaard Annemette,
Siebner Hartwig R.
Publication year - 2014
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24138
Subject(s) - levodopa , dyskinesia , putamen , dopaminergic , parkinson's disease , psychology , medicine , dopamine , movement disorders , anesthesia , neuroscience , functional magnetic resonance imaging , akathisia , disease , psychiatry , schizophrenia (object oriented programming) , antipsychotic
Objective In Parkinson disease (PD), long‐term treatment with the dopamine precursor levodopa gradually induces involuntary “dyskinesia” movements. The neural mechanisms underlying the emergence of levodopa‐induced dyskinesias in vivo are still poorly understood. Here, we applied functional magnetic resonance imaging (fMRI) to map the emergence of peak‐of‐dose dyskinesias in patients with PD. Methods Thirteen PD patients with dyskinesias and 13 PD patients without dyskinesias received 200mg fast‐acting oral levodopa following prolonged withdrawal from their normal dopaminergic medication. Immediately before and after levodopa intake, we performed fMRI, while patients produced a mouse click with the right or left hand or no action (No‐Go) contingent on 3 arbitrary cues. The scan was continued for 45 minutes after levodopa intake or until dyskinesias emerged. Results During No‐Go trials, PD patients who would later develop dyskinesias showed an abnormal gradual increase of activity in the presupplementary motor area (preSMA) and the bilateral putamen. This hyperactivity emerged during the first 20 minutes after levodopa intake. At the individual level, the excessive No‐Go activity in the predyskinesia period predicted whether an individual patient would subsequently develop dyskinesias ( p < 0.001) as well as severity of their day‐to‐day symptomatic dyskinesias ( p < 0.001). Interpretation PD patients with dyskinesias display an immediate hypersensitivity of preSMA and putamen to levodopa, which heralds the failure of neural networks to suppress involuntary dyskinetic movements. Ann Neurol 2014;75:829–836