  Patients with idiopathic generalised epilepsy (IGE) typically have normal
conventional magnetic resonance imaging (MRI), hence MRI based diagnosis 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
tissue. Analysing white matter structures of 32 subjects we incorporated our
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.
