Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

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Standard

Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans. / Herz, Damian M; Haagensen, Brian N; Christensen, Mark Schram; Madsen, Kristoffer H; Rowe, James B; Løkkegaard, Annemette; Siebner, Hartwig R.

I: Brain, Bind 138, Nr. 6, 2015, s. 1658-1666.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Herz, DM, Haagensen, BN, Christensen, MS, Madsen, KH, Rowe, JB, Løkkegaard, A & Siebner, HR 2015, 'Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans', Brain, bind 138, nr. 6, s. 1658-1666. https://doi.org/10.1093/brain/awv096

APA

Herz, D. M., Haagensen, B. N., Christensen, M. S., Madsen, K. H., Rowe, J. B., Løkkegaard, A., & Siebner, H. R. (2015). Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans. Brain, 138(6), 1658-1666. https://doi.org/10.1093/brain/awv096

Vancouver

Herz DM, Haagensen BN, Christensen MS, Madsen KH, Rowe JB, Løkkegaard A o.a. Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans. Brain. 2015;138(6):1658-1666. https://doi.org/10.1093/brain/awv096

Author

Herz, Damian M ; Haagensen, Brian N ; Christensen, Mark Schram ; Madsen, Kristoffer H ; Rowe, James B ; Løkkegaard, Annemette ; Siebner, Hartwig R. / Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans. I: Brain. 2015 ; Bind 138, Nr. 6. s. 1658-1666.

Bibtex

@article{08f9a71f8ab448bf8697108e12f666a1,
title = "Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans",
abstract = "Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements.",
author = "Herz, {Damian M} and Haagensen, {Brian N} and Christensen, {Mark Schram} and Madsen, {Kristoffer H} and Rowe, {James B} and Annemette L{\o}kkegaard and Siebner, {Hartwig R}",
note = "CURIS 2015 NEXS 170",
year = "2015",
doi = "10.1093/brain/awv096",
language = "English",
volume = "138",
pages = "1658--1666",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Abnormal dopaminergic modulation of striato-cortical networks underlies levodopa-induced dyskinesias in humans

AU - Herz, Damian M

AU - Haagensen, Brian N

AU - Christensen, Mark Schram

AU - Madsen, Kristoffer H

AU - Rowe, James B

AU - Løkkegaard, Annemette

AU - Siebner, Hartwig R

N1 - CURIS 2015 NEXS 170

PY - 2015

Y1 - 2015

N2 - Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements.

AB - Dopaminergic signalling in the striatum contributes to reinforcement of actions and motivational enhancement of motor vigour. Parkinson's disease leads to progressive dopaminergic denervation of the striatum, impairing the function of cortico-basal ganglia networks. While levodopa therapy alleviates basal ganglia dysfunction in Parkinson's disease, it often elicits involuntary movements, referred to as levodopa-induced peak-of-dose dyskinesias. Here, we used a novel pharmacodynamic neuroimaging approach to identify the changes in cortico-basal ganglia connectivity that herald the emergence of levodopa-induced dyskinesias. Twenty-six patients with Parkinson's disease (age range: 51-84 years; 11 females) received a single dose of levodopa and then performed a task in which they had to produce or suppress a movement in response to visual cues. Task-related activity was continuously mapped with functional magnetic resonance imaging. Dynamic causal modelling was applied to assess levodopa-induced modulation of effective connectivity between the pre-supplementary motor area, primary motor cortex and putamen when patients suppressed a motor response. Bayesian model selection revealed that patients who later developed levodopa-induced dyskinesias, but not patients without dyskinesias, showed a linear increase in connectivity between the putamen and primary motor cortex after levodopa intake during movement suppression. Individual dyskinesia severity was predicted by levodopa-induced modulation of striato-cortical feedback connections from putamen to the pre-supplementary motor area (Pcorrected = 0.020) and primary motor cortex (Pcorrected = 0.044), but not feed-forward connections from the cortex to the putamen. Our results identify for the first time, aberrant dopaminergic modulation of striatal-cortical connectivity as a neural signature of levodopa-induced dyskinesias in humans. We argue that excessive striato-cortical connectivity in response to levodopa produces an aberrant reinforcement signal producing an abnormal motor drive that ultimately triggers involuntary movements.

U2 - 10.1093/brain/awv096

DO - 10.1093/brain/awv096

M3 - Journal article

VL - 138

SP - 1658

EP - 1666

JO - Brain

JF - Brain

SN - 0006-8950

IS - 6

ER -

ID: 137278644