High-resolution multimodal profiling of human epileptic brain activity via explanted depth electrodes

Area of Science:

• Neuroscience
• Molecular Biology
• Epilepsy Research

Background:

• Integrating electrophysiological and molecular data from the living brain is crucial for understanding neurological diseases like epilepsy.
• Intracranial stereo electroencephalography (SEEG) electrodes, used to pinpoint seizure origins, offer a unique opportunity for multimodal data integration.

Purpose of the Study:

• To introduce and validate a novel method, multimodal profiling of epileptic brain activity via explanted depth electrodes (MoPEDE), for analyzing molecular data from SEEG electrodes.
• To investigate the correlation between molecular profiles (gene expression, DNA methylation) and neurophysiological data in epileptic brain tissue.
• To identify novel molecular markers and epigenetic signatures associated with epilepsy and seizure activity.

Main Methods:

• Explanted SEEG electrodes from epilepsy patients were analyzed using the MoPEDE method.
• Comprehensive molecular profiling included recovery of protein-coding transcripts, cell type markers, DNA methylation, and short variant profiles.
• Data were integrated with electrophysiological and radiological data for high-resolution brain structure and function reconstruction.

Main Results:

• Gene expression gradients correlated with neurophysiology-assigned epileptogenicity indices.
• Outlier molecular fingerprints in some electrodes suggested potential seizure generation or propagation zones missed by clinical assessments.
• DNA methylation profiles indicated distinct chromatin states, and identified novel differentially expressed and methylated genes linked to epilepsy.

Conclusions:

• RNA and genome-wide epigenetic data from explanted SEEG electrodes provide high-resolution molecular landscapes of brain activity.
• The MoPEDE approach validates the utility of SEEG electrodes for molecular analysis in epilepsy.
• This method holds potential for enhancing diagnostic decisions and advancing the understanding of epileptogenic network processes in the human brain.