Computer modelling of connectivity change suggests epileptogenesis mechanisms in idiopathic generalised epilepsy.
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 epileptogenesis is 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 modelling. 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.
['Sinha|Nishant|N|', 'Wang|Yujiang|Y|', 'Dauwels|Justin|J|', 'Kaiser|Marcus|M|', 'Thesen|Thomas|T|', 'Forsyth|Rob|R|', 'Taylor|Peter Neal|PN|']
D000328:Adult D001921:Brain D001931:Brain Mapping D003198:Computer Simulation D056324:Diffusion Tensor Imaging D004829:Epilepsy, Generalized D005260:Female D006801:Humans D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D009415:Nerve Net D009434:Neural Pathways D012640:Seizures D013788:Thalamus D066127:White Matter D055815:Young Adult
Computational model Generalised epilepsy Diagnosis Diffusion MRI Epilepsy mechanism