Thalamo‐Lesional Connectivity Signatures of Bilateral Tonic–Clonic Seizures in Focal Cortical Dysplasia‐Related Epilepsy

OBJECTIVES: Focal cortical dysplasia (FCD) is the most common etiology of drug-resistant epilepsy in children. Focal to bilateral tonic-clonic seizures (FBTCS) mark a high risk of drug-resistant epilepsy and involve thalamocortical circuitry in their generation and propagation. Using FCD as a model of focal epilepsy, we examined the integrity of thalamocortical circuitry to characterize thalamo-lesional connectivity signatures of FBTCS. METHODS: Forty-three patients (14 with FBTCS) range 5-22 years, and 116 age- and sex-matched healthy controls were included. A network-driven thalamic functional parcellation was developed in healthy controls using Yeo 7-network atlas. We calculated z-scored thalamo-lesional functional connectivity between thalamic functional parcels and dysplasia masks in reference to controls, which was used to classify the presence of FBTCS. Clinical associations of thalamo-lesional connectivity were evaluated. RESULTS: Z-scored thalamo-lesional connectivity classified the presence of FBTCS with a median accuracy of 0.72. The thalamic parcel preferentially connected to the somatomotor-network (SMN), comprising ventral-posterolateral, pulvinar-medial and intralaminar nuclei, contributed most to classification. Lower ipsilateral SMN-thalamus connectivity was related to postsurgical seizure freedom and preserved ipsilateral thalamic volume. SIGNIFICANCE: Thalamocortical circuitry was examined between the seizure generator (lesion) and the amplifier (thalamus) in FCD patients. FBTCS are associated with thalamo-lesional connectivity abnormalities that correlate to postsurgical outcomes, and demonstrate the SMN-thalamus as a primary gatekeeper for secondary generalization. The successful implementation of our classifier suggests that these thalamo-lesional signatures can serve as a potential neuromarker for seizure phenotyping, marking a step toward network-informed, personalized treatment.