Linking Cortical Morphometry in Self-Limited Epilepsy With Centrotemporal Spikes to Cognition, Function, and Molecular Architecture

Aims

Self-limiting epilepsy with centrotemporal spikes (SeLECTS) is the most common type of pediatric epilepsy, characterized by age-dependent seizures, which usually occur during the development of a child's brain. This condition is associated with heterogeneous neurodevelopmental alterations, including cortical thinning, changes in subcortical structures, and atypical development linked to the disease.

Methods

To establish an integrative model of neurodevelopment in SeLECTS, we investigated how its structural brain alterations are linked to clinical phenotypes, aberrant brain network function, and the local molecular architecture. Using normative modeling, we analyzed magnetic resonance imaging (MRI)-derived morphometric features, specifically cortical thickness and subcortical volumes, in a multicenter preschool cohort (devCCNP, n = 457) and a SeLECTS cohort (n = 187) and generated deviation matrices specific to SeLECTS.

Results

Nonnegative matrix factorization was applied to decompose these matrices into eight deviation components, revealing biologically interpretable patterns of heterogeneity, along with subject-specific loadings that quantify the expression of these components in individual subjects. Behavioral partial least squares analysis identified significant associations between subject-specific loadings and phenotypic profiles in SeLECTS, suggesting that factors such as age, medication history, and disease duration are important for morphological development—particularly in temporal and frontal regions associated with cognitive control and language. Furthermore, we explored the molecular basis of the morphometric deviation components by mapping their spatial expression to features related to functional cognition, neurotransmitter/transcript profiles, and mitochondrial characteristics.

Conclusion

Collectively, this study provides a novel framework for elucidating the neuroanatomical heterogeneity of epilepsy, offering insights into its behavioral and molecular correlates.