Distinct Functional Cortico-Striato-Thalamo-Cerebellar Networks in Genetic Generalized and Focal Epilepsies with Generalized Tonic-Clonic Seizures

This study aimed to delineate cortico-striato-thalamo-cerebellar network profiles based on static and dynamic connectivity analysis in genetic generalized and focal epilepsies with generalized tonic-clonic seizures, and to evaluate its potential for distinguishing these two epilepsy syndromes. A total of 342 individuals participated in the study (114 patients with genetic generalized epilepsy with generalized tonic-clonic seizures (GE-GTCS), and 114 age- and sex-matched patients with focal epilepsy with focal to bilateral tonic-clonic seizure (FE-FBTS), 114 healthy controls). Resting-state fMRI data were examined through static and dynamic functional connectivity (dFC) analyses, constructing cortico-striato-thalamo-cerebellar networks. Network patterns were compared between groups, and were correlated to epilepsy duration. A pattern-learning algorithm was applied to network features for classifying both epilepsy syndromes. FE-FBTS and GE-GTCS both presented with altered functional connectivity in subregions of the motor/premotor and somatosensory networks. Among these two groups, the connectivity within the cerebellum increased in the static, while the dFC variability decreased; conversely, the connectivity of the thalamus decreased in FE-FBTS and increased in GE-GTCS in the static state. Connectivity differences between patient groups were mainly located in the thalamus and cerebellum, and correlated with epilepsy duration. Support vector machine (SVM) classification had accuracies of 66.67%, 68.42%, and 77.19% when using static, dynamic, and combined approaches to categorize GE-GTCS and FE-GTCS. Network features with high discriminative ability predominated in the thalamic and cerebellar connectivities. The network embedding of the thalamus and cerebellum likely plays an important differential role in GE-GTCS and FE-FBTS, and could serve as an imaging biomarker for differential diagnosis.