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Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges

Vaudano, AE; Laufs, H; Kiebel, SJ; Carmichael, DW; Hamandi, K; Guye, M; Thornton, R; ... Lemieux, L; + view all (2009) Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges. PLOS ONE , 4 (8) , Article e6475. 10.1371/journal.pone.0006475. Green open access

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Abstract

Background: Generalised spike wave (GSW) discharges are the electroencephalographic ( EEG) hallmark of absence seizures, clinically characterised by a transitory interruption of ongoing activities and impaired consciousness, occurring during states of reduced awareness. Several theories have been proposed to explain the pathophysiology of GSW discharges and the role of thalamus and cortex as generators. In this work we extend the existing theories by hypothesizing a role for the precuneus, a brain region neglected in previous works on GSW generation but already known to be linked to consciousness and awareness. We analysed fMRI data using dynamic causal modelling (DCM) to investigate the effective connectivity between precuneus, thalamus and prefrontal cortex in patients with GSW discharges.Methodology and Principal Findings: We analysed fMRI data from seven patients affected by Idiopathic Generalized Epilepsy (IGE) with frequent GSW discharges and significant GSW-correlated haemodynamic signal changes in the thalamus, the prefrontal cortex and the precuneus. Using DCM we assessed their effective connectivity, i.e. which region drives another region. Three dynamic causal models were constructed: GSW was modelled as autonomous input to the thalamus (model A), ventromedial prefrontal cortex (model B), and precuneus (model C). Bayesian model comparison revealed Model C (GSW as autonomous input to precuneus), to be the best in 5 patients while model A prevailed in two cases. At the group level model C dominated and at the population-level the p value of model C was -1.Conclusion: Our results provide strong evidence that activity in the precuneus gates GSW discharges in the thalamo(fronto) cortical network. This study is the first demonstration of a causal link between haemodynamic changes in the precuneus - an index of awareness - and the occurrence of pathological discharges in epilepsy.

Type: Article
Title: Causal Hierarchy within the Thalamo-Cortical Network in Spike and Wave Discharges
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0006475
Publisher version: http://dx.doi.org/10.1371/journal.pone.0006475
Language: English
Additional information: © 2009 Vaudano 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. This work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. The work was partly funded through grants European Federation of Neurological Society (EFNS) (to AEV), Medical Research Council (MRC grant number G0301067 to AEV, DC, RR and RT), the Wellcome Trust (grant number 067176 to KH; grant number 056750 to KF and SK), the Deutsche Forschungsgemeinschaft (LA 1452/3-1 to HL) and Bundesministerium für Bildung und Forschung (01 EV 0703 to HL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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 > Clinical and Experimental Epilepsy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Imaging Neuroscience
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
URI: https://discovery.ucl.ac.uk/id/eprint/152387
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