Alterations in brain connectivity underlying beta oscillations in Parkinsonism.

Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis...

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Main Authors: Rosalyn J Moran, Nicolas Mallet, Vladimir Litvak, Raymond J Dolan, Peter J Magill, Karl J Friston, Peter Brown
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-08-01
Series:PLoS Computational Biology
Online Access:https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002124&type=printable
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author Rosalyn J Moran
Nicolas Mallet
Vladimir Litvak
Raymond J Dolan
Peter J Magill
Karl J Friston
Peter Brown
author_facet Rosalyn J Moran
Nicolas Mallet
Vladimir Litvak
Raymond J Dolan
Peter J Magill
Karl J Friston
Peter Brown
author_sort Rosalyn J Moran
collection DOAJ
description Cortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis remains unclear. Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned rat model of PD to examine the effective connectivity underlying these spectral abnormalities. We acquired auto-spectral and cross-spectral measures of beta oscillations (10-35 Hz) from local field potential recordings made simultaneously in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic nucleus (STN), and used these data to optimise neurobiologically plausible models. Chronic dopamine depletion reorganised the cortico-basal ganglia-thalamocortical circuit, with increased effective connectivity in the pathway from cortex to STN and decreased connectivity from STN to GPe. Moreover, a contribution analysis of the Parkinsonian circuit distinguished between pathogenic and compensatory processes and revealed how effective connectivity along the indirect pathway acquired a strategic importance that underpins beta oscillations. In modelling excessive beta synchrony in PD, these findings provide a novel perspective on how altered connectivity in basal ganglia-thalamocortical circuits reflects a balance between pathogenesis and compensation, and predicts potential new therapeutic targets to overcome dysfunctional oscillations.
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spelling doaj-art-cbbfca784d0b46eb8d9d73514d4fedf52025-08-20T02:22:37ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-08-0178e100212410.1371/journal.pcbi.1002124Alterations in brain connectivity underlying beta oscillations in Parkinsonism.Rosalyn J MoranNicolas MalletVladimir LitvakRaymond J DolanPeter J MagillKarl J FristonPeter BrownCortico-basal ganglia-thalamocortical circuits are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically exaggerated beta oscillations. Abnormal rhythms, found in several circuit nodes are correlated with movement impairments but their neural basis remains unclear. Here, we used dynamic causal modelling (DCM) and the 6-hydroxydopamine-lesioned rat model of PD to examine the effective connectivity underlying these spectral abnormalities. We acquired auto-spectral and cross-spectral measures of beta oscillations (10-35 Hz) from local field potential recordings made simultaneously in the frontal cortex, striatum, external globus pallidus (GPe) and subthalamic nucleus (STN), and used these data to optimise neurobiologically plausible models. Chronic dopamine depletion reorganised the cortico-basal ganglia-thalamocortical circuit, with increased effective connectivity in the pathway from cortex to STN and decreased connectivity from STN to GPe. Moreover, a contribution analysis of the Parkinsonian circuit distinguished between pathogenic and compensatory processes and revealed how effective connectivity along the indirect pathway acquired a strategic importance that underpins beta oscillations. In modelling excessive beta synchrony in PD, these findings provide a novel perspective on how altered connectivity in basal ganglia-thalamocortical circuits reflects a balance between pathogenesis and compensation, and predicts potential new therapeutic targets to overcome dysfunctional oscillations.https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002124&type=printable
spellingShingle Rosalyn J Moran
Nicolas Mallet
Vladimir Litvak
Raymond J Dolan
Peter J Magill
Karl J Friston
Peter Brown
Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
PLoS Computational Biology
title Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
title_full Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
title_fullStr Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
title_full_unstemmed Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
title_short Alterations in brain connectivity underlying beta oscillations in Parkinsonism.
title_sort alterations in brain connectivity underlying beta oscillations in parkinsonism
url https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1002124&type=printable
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