Dysmorphic neurons express markers of inhibitory glycinergic signaling in focal cortical dysplasia IIb.

Journal: Brain pathology (Zurich, Switzerland)
Published Date: Sep 16, 2025

Abstract

Focal cortical dysplasia (FCD) is a neurodevelopmental malformation that often manifests as medically refractory epilepsy. A key histological hallmark of FCD type II is the presence of cytomegalic dysmorphic neurons (CDNs), which are considered to be major contributors to cortical network hyperexcitability. However, the relatively low frequency of CDNs within resected lesions has challenged their unbiased molecular characterization. Here, we leverage deep learning approaches to objectively map key anatomical compartments of FCD IIb and guide regional spatial transcriptomic profiling. Using this approach, we generate an anatomical transcriptional catalog of type IIb FCD, and uncover non-canonical markers of signaling and neurotransmitter pathways in CDNs that may serve as new therapeutic targets for this debilitating disorder.

Authors

  • Ameesha Paliwal
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Kevin Faust
    Department of Computer Science, University of Toronto, 40 St. George Street, Toronto, ON, M5S 2E4, Canada.
  • Okty Abbasi Borhani
    Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Mugeng Liu
    Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Lauren Omoto
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Evelyn Rose Kamski-Hennekam
    Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Parsa Babaei Zadeh
    Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
  • Rifat Shahriar Sajid
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
  • Phedias Diamandis
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, M5S 1A8, Canada. [email protected].

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