Multiple subcortical and subcortico-cortico dynamic network reconfigurations characterize focal-to-bilateral tonic-clonic seizures.

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on inter-ictal resting state fMRI data. A complex set of subcortio-cortico interactions appeared to support the secondary generalization characteristic of FBTCS+ status, specifically integrations involving the caudate and cereb-5 subcortical subsystems with the ventral attention network, suggesting motor and attention system communications are dysregulated. These abnormal subcortico-cortico dynamics were more prominent in current versus a remote history of FBTCS+. We concluded that the inter-ictal state provided a breeding ground for reconfiguring dynamic communication within and between multiple cortical-subcortical systems. These findings broaden our understanding of seizure propagation effects in TLE, pointing toward biomarkers that may mark the transition from focal seizures to the more severe form of TLE (FBTCS +).