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Computer modelling of connectivity change suggests epileptogenesis mechanisms in idiopathic generalised epilepsy

Lookup NU author(s): Nishant Sinha, Dr Yujiang WangORCiD, Professor Marcus Kaiser, Dr Rob ForsythORCiD, Dr Peter TaylorORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Patients with idiopathic generalised epilepsy (IGE) typically have normal conventional magnetic resonance imaging (MRI), hence diagnosis based on MRI is challenging. Anatomical abnormalities underlying brain dysfunctions in IGE are unclear and their relation to the pathomechanisms of epileptogenesisis poorly understood. In this study, we applied connectometry, an advanced quantitative neuroimaging technique for investigating localised changes in white-matter tissues in vivo. Analysing white matter structures of 32 subjects we incorporated our in vivo findings in a computational model of seizure dynamics to suggest a plausible mechanism of epileptogenesis. Patients with IGE have significant bilateral alterations in major white-matter fascicles. In the cingulum, fornix, and superior longitudinal fasciculus, tract integrity is compromised, whereas in specific parts of tracts between thalamus and the precentral gyrus, tract integrity is enhanced in patients. Combining these alterations in a logistic regression model, we computed the decision boundary that discriminated patients and controls. The computational model, informed with the findings on the tract abnormalities, specifically highlighted the importance of enhanced cortico-reticular connections along with impaired cortico-cortical connections in inducing pathological seizure-like dynamics.We emphasise taking directionality of brain connectivity into consideration towards understanding the pathological mechanisms; this is possible by combining neuroimaging and computational mod-elling. Our imaging evidence of structural alterations suggest the loss of cortico-cortical and enhancement of cortico-thalamic fibre integrity in IGE. We further suggest that impaired connectivity from cortical regions to the thalamic reticular nucleus offers a therapeutic target for selectively modifying the brain circuit for reversing the mechanisms leading to epileptogenesis

Publication metadata

Author(s): Sinha N, Wang Y, Dauwels J, Kaiser M, Thesene T, Forsyth R, Taylor PN

Publication type: Article

Publication status: Published

Journal: NeuroImage: Clinical

Year: 2019

Volume: 21

Online publication date: 11/01/2019

Acceptance date: 03/01/2019

Date deposited: 08/01/2019

ISSN (electronic): 2213-1582

Publisher: Elsevier BV


DOI: 10.1016/j.nicl.2019.101655


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Funder referenceFunder name
105617/Z/14/ZWellcome Trust (closed comp)
210109/Z/18/ZWellcome Trust