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Abstracts & Posters

Vol. 1 No. S1 (2025): Special Issue: 2025 Geisel Research Poster Night

Single-Nuclei RNA Sequencing Reveals Inhibitory Network Dysregulation in Focal Cortical Dysplasia

Submitted
19 December 2025
Published
27-12-2025

Abstract

Focal cortical dysplasia (FCD) is a leading cause of drug-resistant epilepsy, driven largely by somatic mutations that hyperactivate the mTOR pathway and disrupt neural circuitry. This study compiled single-nuclei RNA sequencing datasets from five published reports to analyze inhibitory neuron populations within temporal lobe specimens from patients with FCD, non-FCD epilepsy, and non-epileptic controls. After batch correction and quality filtering, analyses revealed a significant reduction in GABAergic neurons and interneurons in FCD samples, accompanied by the emergence of a dysmorphic neuronal population expressing early progenitor markers. mTOR pathway elements, particularly S6, were markedly upregulated in dysmorphic neurons. These findings reinforce the central role of mTOR dysregulation in FCD pathogenesis and highlight candidate cellular markers for further investigation. Future work will validate findings in Dartmouth surgical specimens and explore neuroinflammatory and extracellular matrix pathways contributing to epileptogenesis.

References

  1. References are available on the poster PDF.