An optimal strategy for epilepsy surgery: Disruption of the rich-club?
PLoS Computational Biology
Public Library of Science
Copyright: © 2017 Lopes 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.
Surgery is a therapeutic option for people with epilepsy whose seizures are not controlled by anti-epilepsy drugs. In pre-surgical planning, an array of data modalities, often including intra-cranial EEG, is used in an attempt to map regions of the brain thought to be crucial for the generation of seizures. These regions are then resected with the hope that the individual is rendered seizure free as a consequence. However, post-operative seizure freedom is currently sub-optimal, suggesting that the pre-surgical assessment may be improved by taking advantage of a mechanistic understanding of seizure generation in large brain networks. Herein we use mathematical models to uncover the relative contribution of regions of the brain to seizure generation and consequently which brain regions should be considered for resection. A critical advantage of this modeling approach is that the effect of different surgical strategies can be predicted and quantitatively compared in advance of surgery. Herein we seek to understand seizure generation in networks with different topologies and study how the removal of different nodes in these networks reduces the occurrence of seizures. Since this a computationally demanding problem, a first step for this aim is to facilitate tractability of this approach for large networks. To do this, we demonstrate that predictions arising from a neural mass model are preserved in a lower dimensional, canonical model that is quicker to simulate. We then use this simpler model to study the emergence of seizures in artificial networks with different topologies, and calculate which nodes should be removed to render the network seizure free. We find that for scale-free and rich-club networks there exist specific nodes that are critical for seizure generation and should therefore be removed, whereas for small-world networks the strategy should instead focus on removing sufficient brain tissue. We demonstrate the validity of our approach by analysing intra-cranial EEG recordings from a database comprising 16 patients who have undergone epilepsy surgery, revealing rich-club structures within the obtained functional networks. We show that the postsurgical outcome for these patients was better when a greater proportion of the rich club was removed, in agreement with our theoretical predictions.
MAL, MG, MPR and JRT gratefully acknowledge funding from the Medical Research Council via grant MR/K013998/1. MG, MPR and JRT further acknowledge the financial support of the EPSRC via grant EP/N014391/1. The contribution of MG and JRT was further generously supported by a Wellcome Trust Institutional Strategic Support Award (WT105618MA). MPR and EA are supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust. KS gratefully acknowledges support by the Swiss National Science Foundation (SNF 32003B_155950). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
This is the final version of the article. Available from Public Library of Science via the DOI in this record.
Data are publicly available at https://ore.exeter.ac.uk/repository/handle/10871/28196.
Vol. 13, Iss. 8, pp. e1005637 -
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