A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.

People with Alzheimer's disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. Leading hypotheses largely consider hyperexcitability of local cortical tissue as primarily responsible for increased seizure prevalence in AD. However, in the general populati...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Luke Tait, Marinho A Lopes, George Stothart, John Baker, Nina Kazanina, Jiaxiang Zhang, Marc Goodfellow
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fb4fefbd8bd04886954db0583ba7e548
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fb4fefbd8bd04886954db0583ba7e548
record_format	dspace
spelling	oai:doaj.org-article:fb4fefbd8bd04886954db0583ba7e5482021-12-02T19:58:06ZA large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.1553-734X1553-735810.1371/journal.pcbi.1009252https://doaj.org/article/fb4fefbd8bd04886954db0583ba7e5482021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009252https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358People with Alzheimer's disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. Leading hypotheses largely consider hyperexcitability of local cortical tissue as primarily responsible for increased seizure prevalence in AD. However, in the general population of people with epilepsy, large-scale brain network organization additionally plays a role in determining seizure likelihood and phenotype. Here, we propose that alterations to large-scale brain network organization seen in AD may contribute to increased seizure likelihood. To test this hypothesis, we combine computational modelling with electrophysiological data using an approach that has proved informative in clinical epilepsy cohorts without AD. EEG was recorded from 21 people with probable AD and 26 healthy controls. At the time of EEG acquisition, all participants were free from seizures. Whole brain functional connectivity derived from source-reconstructed EEG recordings was used to build subject-specific brain network models of seizure transitions. As cortical tissue excitability was increased in the simulations, AD simulations were more likely to transition into seizures than simulations from healthy controls, suggesting an increased group-level probability of developing seizures at a future time for AD participants. We subsequently used the model to assess seizure propensity of different regions across the cortex. We found the most important regions for seizure generation were those typically burdened by amyloid-beta at the early stages of AD, as previously reported by in-vivo and post-mortem staging of amyloid plaques. Analysis of these spatial distributions also give potential insight into mechanisms of increased susceptibility to generalized (as opposed to focal) seizures in AD vs controls. This research suggests avenues for future studies testing patients with seizures, e.g. co-morbid AD/epilepsy patients, and comparisons with PET and MRI scans to relate regional seizure propensity with AD pathologies.Luke TaitMarinho A LopesGeorge StothartJohn BakerNina KazaninaJiaxiang ZhangMarc GoodfellowPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 8, p e1009252 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Luke Tait Marinho A Lopes George Stothart John Baker Nina Kazanina Jiaxiang Zhang Marc Goodfellow A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
description	People with Alzheimer's disease (AD) are 6-10 times more likely to develop seizures than the healthy aging population. Leading hypotheses largely consider hyperexcitability of local cortical tissue as primarily responsible for increased seizure prevalence in AD. However, in the general population of people with epilepsy, large-scale brain network organization additionally plays a role in determining seizure likelihood and phenotype. Here, we propose that alterations to large-scale brain network organization seen in AD may contribute to increased seizure likelihood. To test this hypothesis, we combine computational modelling with electrophysiological data using an approach that has proved informative in clinical epilepsy cohorts without AD. EEG was recorded from 21 people with probable AD and 26 healthy controls. At the time of EEG acquisition, all participants were free from seizures. Whole brain functional connectivity derived from source-reconstructed EEG recordings was used to build subject-specific brain network models of seizure transitions. As cortical tissue excitability was increased in the simulations, AD simulations were more likely to transition into seizures than simulations from healthy controls, suggesting an increased group-level probability of developing seizures at a future time for AD participants. We subsequently used the model to assess seizure propensity of different regions across the cortex. We found the most important regions for seizure generation were those typically burdened by amyloid-beta at the early stages of AD, as previously reported by in-vivo and post-mortem staging of amyloid plaques. Analysis of these spatial distributions also give potential insight into mechanisms of increased susceptibility to generalized (as opposed to focal) seizures in AD vs controls. This research suggests avenues for future studies testing patients with seizures, e.g. co-morbid AD/epilepsy patients, and comparisons with PET and MRI scans to relate regional seizure propensity with AD pathologies.
format	article
author	Luke Tait Marinho A Lopes George Stothart John Baker Nina Kazanina Jiaxiang Zhang Marc Goodfellow
author_facet	Luke Tait Marinho A Lopes George Stothart John Baker Nina Kazanina Jiaxiang Zhang Marc Goodfellow
author_sort	Luke Tait
title	A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
title_short	A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
title_full	A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
title_fullStr	A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
title_full_unstemmed	A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.
title_sort	large-scale brain network mechanism for increased seizure propensity in alzheimer's disease.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/fb4fefbd8bd04886954db0583ba7e548
work_keys_str_mv	AT luketait alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT marinhoalopes alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT georgestothart alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT johnbaker alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT ninakazanina alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT jiaxiangzhang alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT marcgoodfellow alargescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT luketait largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT marinhoalopes largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT georgestothart largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT johnbaker largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT ninakazanina largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT jiaxiangzhang largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease AT marcgoodfellow largescalebrainnetworkmechanismforincreasedseizurepropensityinalzheimersdisease
_version_	1718375817867689984

A large-scale brain network mechanism for increased seizure propensity in Alzheimer's disease.

Ejemplares similares