Moran, RJ;
Mallet, N;
Litvak, V;
Dolan, RJ;
Magill, PJ;
Friston, KJ;
Brown, P;
(2011)
Alterations in Brain Connectivity Underlying Beta Oscillations in Parkinsonism.
PLOS COMPUT BIOL
, 7
(8)
, Article e1002124. 10.1371/journal.pcbi.1002124.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Alterations in Brain Connectivity Underlying Beta Oscillations in Parkinsonism |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pcbi.1002124 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pcbi.1002124 |
| Language: | English |
| Additional information: | © 2011 Moran et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. RJM was funded by an Award from the Max Planck Society to RJD. RJD and KJF are funded by the Wellcome Trust. NM, PJM and PB are funded by the Medical Research Council UK, Wellcome Trust, Rosetrees Trust, The Dana Foundation USA and Parkinson's UK (grant number G-0806). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | EXTERNAL GLOBUS-PALLIDUS, DYNAMIC CAUSAL-MODELS, NEURAL MASS MODEL, SUBTHALAMIC NUCLEUS, BASAL GANGLIA, CEREBRAL-CORTEX, PATHOLOGICAL SYNCHRONIZATION, FREQUENCY STIMULATION, BIFURCATION-ANALYSIS, SPECTRAL RESPONSES |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1318791 |
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