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

Authors:
Open Access
Publisher website
Google Scholar
Abstract
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.
Funding Information
  • National Center for Advancing Translational Sciences (P50 HD105328)
  • National Institute of Neurological Disorders and Stroke (K23NS131522)
  • American Epilepsy Society
  • American Academy of Neurology

This publication has 43 references indexed in Scilit: