Multimodal mapping of regional brain vulnerability to focal cortical dysplasia

Hyo M. Lee, Seok Jun Hong, Ravnoor Gill, Benoit Caldairou, Irene Wang, Jian Guo Zhang, Francesco Deleo, Dewi Schrader, Fabrice Bartolomei, Maxime Guye, Kyoo Ho Cho, Carmen Barba, Sanjay Sisodiya, Graeme Jackson, R. Edward Hogan, Lily Wong-Kisiel, Gregory D. Cascino, Andreas Schulze-Bonhage, Iscia Lopes-Cendes, Fernando CendesRenzo Guerrini, Boris Bernhardt, Neda Bernasconi, Andrea Bernasconi

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Focal cortical dysplasia (FCD) type II is a highly epileptogenic developmental malformation and a common cause of surgically treated drug-resistant epilepsy. While clinical observations suggest frequent occurrence in the frontal lobe, mechanisms for such propensity remain unexplored. Here, we hypothesized that cortex-wide spatial associations of FCD distribution with cortical cytoarchitecture, gene expression and organizational axes may offer complementary insights into processes that predispose given cortical regions to harbour FCD. We mapped the cortex-wide MRI distribution of FCDs in 337 patients collected from 13 sites worldwide. We then determined its associations with (i) cytoarchitectural features using histological atlases by Von Economo and Koskinas and BigBrain; (ii) whole-brain gene expression and spatiotemporal dynamics from prenatal to adulthood stages using the Allen Human Brain Atlas and PsychENCODE BrainSpan; and (iii) macroscale developmental axes of cortical organization. FCD lesions were preferentially located in the prefrontal and fronto-limbic cortices typified by low neuron density, large soma and thick grey matter. Transcriptomic associations with FCD distribution uncovered a prenatal component related to neuroglial proliferation and differentiation, likely accounting for the dysplastic makeup, and a postnatal component related to synaptogenesis and circuit organization, possibly contributing to circuit-level hyperexcitability. FCD distribution showed a strong association with the anterior region of the antero-posterior axis derived from heritability analysis of interregional structural covariance of cortical thickness, but not with structural and functional hierarchical axes. Reliability of all results was confirmed through resampling techniques. Multimodal associations with cytoarchitecture, gene expression and axes of cortical organization indicate that prenatal neurogenesis and postnatal synaptogenesis may be key points of developmental vulnerability of the frontal lobe to FCD. Concordant with a causal role of atypical neuroglial proliferation and growth, our results indicate that FCD-vulnerable cortices display properties indicative of earlier termination of neurogenesis and initiation of cell growth. They also suggest a potential contribution of aberrant postnatal synaptogenesis and circuit development to FCD epileptogenicity.

Original languageEnglish
Pages (from-to)3404-3415
Number of pages12
JournalBrain
Volume146
Issue number8
DOIs
StatePublished - Aug 1 2023

Keywords

  • MRI
  • epilepsy
  • focal cortical dysplasia
  • imaging-genetics
  • neurodevelopment

Fingerprint

Dive into the research topics of 'Multimodal mapping of regional brain vulnerability to focal cortical dysplasia'. Together they form a unique fingerprint.

Cite this