Brain mosaicism in epileptogenic cortical malformations
Wednesday, February 1, 2023
18:00 UTC
Prof Stéphanie Baulac
ICM Paris
Recording
Open recording
Hosted by Clinical and Experimental Epilepsy70 minutes
Abstract
Focal Cortical Dysplasia (FCD) is the most common focal cortical malformation leading to intractable childhood focal epilepsy. In recent years, we and others have shown that FCD type II is caused by mosaic mutations in genes within the PI3K-AKT-mTOR-signaling pathway. Hyperactivation of the mTOR pathway accounts for neuropathological abnormalities and seizure occurrence in FCD. We further showed from human surgical FCDII tissue that epileptiform activity correlates with the density of mutated dysmorphic neurons, supporting their pro-epileptogenic role. The level of mosaicism, as defined by variant allele frequency (VAF) is thought to correlate with the size and regional brain distribution of the lesion such that when a somatic mutation occurs early during the cortical development, the dysplastic area is smaller than if it occurs later. Novel approaches based on the detection of cell-free DNA from the CSF and from trace tissue adherent to SEEG electrodes promise future opportunities for genetic testing during the presurgical evaluation of refractory epilepsy patients or in those that are not eligible for surgery. In utero-based electroporation mouse models allow to express somatic mutation during neurodevelopment and recapitulate most neuropathological and clinical features of FCDII, establishing relevant preclinical mouse models for developing precision medicine strategies.
Topics
Related Seminars
SeminarSeminarSeminar
Finding Meaning in Memories
Daphna Shohamy and Ashok Litwin-Kumar bridge experimental and computational neuroscience to explain how the brain assigns significance to memories, how dopamine shapes memory-guided decisions, and…
Upcoming · Sep 16, 2026
Columbia University Zuckerman Institute
Deciphering the Dynamics of the Unconscious Brain under General Anesthesia
Stanford Neurosciences Seminar Series talk by Emery Brown (Massachusetts Institute of Technology, Neuroscience Statistics Research Lab) on deciphering the dynamics of the unconscious brain under…
Upcoming · Sep 17, 2026
Wu Tsai Neurosciences Institute, Stanford University
The Connectome in Use: From anatomical wiring to functional organization in the behaving C. elegans brain
Rani Borbara presents brain-wide recordings from more than 150 freely moving C. elegans to examine how anatomical connectivity becomes functional organization during behavior. Cross-animal models…
Upcoming · Sep 18, 2026
MIT Simons Center for the Social Brain
Related Job Opportunities
JobJobJob
Postdoctoral Scientist - Sarvestani Lab
The Sarvestani Lab at Cornell University is recruiting a postdoctoral scientist in systems neuroscience to study how visual and motor systems across the brain and body support perception and…
Posted Aug 12, 2026
Ithaca, New York, United States
PhD Studentship: Mitochondrial Metabolism and Novel Therapeutic Strategies for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) (Fixed Term)
Supervisors: Professor Andrew Murray, Department of Physiology, Development and Neuroscience, University of Cambridge Dr Ross Lindsay, Novo Nordisk Funding: Fully funded PhD studentship (Home/UK…
Posted Aug 10, 2026
Research Associate (Fixed Term)
We seek a highly motivated Postdoctoral Research Associate to join the laboratory of Professor Kathy Niakan. We are based in the Loke Centre for Trophoblast Research (LCTR), in the Department of…
Posted Aug 11, 2026