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Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy?
At least one-third of all people with epilepsy have seizures that remain poorly controlled despite an increasing number of available anti-epileptic drugs (AEDs). Often, there is an initial good response to a newly introduced AED, which may last up to months, eventually followed by the return of seiz...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Academic Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581121/ https://www.ncbi.nlm.nih.gov/pubmed/30981121 http://dx.doi.org/10.1016/j.yebeh.2019.03.003 |
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author | Woldman, Wessel Cook, Mark J. Terry, John R. |
author_facet | Woldman, Wessel Cook, Mark J. Terry, John R. |
author_sort | Woldman, Wessel |
collection | PubMed |
description | At least one-third of all people with epilepsy have seizures that remain poorly controlled despite an increasing number of available anti-epileptic drugs (AEDs). Often, there is an initial good response to a newly introduced AED, which may last up to months, eventually followed by the return of seizures thought to be due to the development of tolerance. We introduce a framework within which the interplay between AED response and brain networks can be explored to understand the development of tolerance. We use a computer model for seizure generation in the context of dynamic networks, which allows us to generate an ‘in silico’ electroencephalogram (EEG). This allows us to study the effect of changes in excitability network structure and intrinsic model properties on the overall seizure likelihood. Within this framework, tolerance to AEDs – return of seizure-like activity – may occur in 3 different scenarios: 1) the efficacy of the drug diminishes while the brain network remains relatively constant; 2) the efficacy of the drug remains constant, but connections between brain regions change; 3) the efficacy of the drug remains constant, but the intrinsic excitability within brain regions varies dynamically. We argue that these latter scenarios may contribute to a deeper understanding of how drug resistance to AEDs may occur. |
format | Online Article Text |
id | pubmed-6581121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Academic Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-65811212019-06-24 Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? Woldman, Wessel Cook, Mark J. Terry, John R. Epilepsy Behav Article At least one-third of all people with epilepsy have seizures that remain poorly controlled despite an increasing number of available anti-epileptic drugs (AEDs). Often, there is an initial good response to a newly introduced AED, which may last up to months, eventually followed by the return of seizures thought to be due to the development of tolerance. We introduce a framework within which the interplay between AED response and brain networks can be explored to understand the development of tolerance. We use a computer model for seizure generation in the context of dynamic networks, which allows us to generate an ‘in silico’ electroencephalogram (EEG). This allows us to study the effect of changes in excitability network structure and intrinsic model properties on the overall seizure likelihood. Within this framework, tolerance to AEDs – return of seizure-like activity – may occur in 3 different scenarios: 1) the efficacy of the drug diminishes while the brain network remains relatively constant; 2) the efficacy of the drug remains constant, but connections between brain regions change; 3) the efficacy of the drug remains constant, but the intrinsic excitability within brain regions varies dynamically. We argue that these latter scenarios may contribute to a deeper understanding of how drug resistance to AEDs may occur. Academic Press 2019-05 /pmc/articles/PMC6581121/ /pubmed/30981121 http://dx.doi.org/10.1016/j.yebeh.2019.03.003 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Woldman, Wessel Cook, Mark J. Terry, John R. Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title | Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title_full | Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title_fullStr | Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title_full_unstemmed | Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title_short | Evolving dynamic networks: An underlying mechanism of drug resistance in epilepsy? |
title_sort | evolving dynamic networks: an underlying mechanism of drug resistance in epilepsy? |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581121/ https://www.ncbi.nlm.nih.gov/pubmed/30981121 http://dx.doi.org/10.1016/j.yebeh.2019.03.003 |
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