Understanding, diagnosing and treating brain disease is a scientific, health and societal priority. Treatment-resistant seizures afflict one in three people living with epilepsy and are a major cause of disability and morbidity. Epilepsy surgery is the single most effective potentially curative treatment but 30-60% of patients still fail surgery as not all the epileptic network is removed. In complex cases, stereoelectroencephalography (SEEG) with robot-assisted depth electrode implantation helps localize seizure foci. We recently discovered that removed SEEG electrodes retain trace molecular material including ribonucleic acids, allowing for transcriptomic and epigenetic profiling of brain states.
Our central hypothesis is that RNAs on the surface of explanted SEEG electrodes from humans with epilepsy can tell us about the pathophysiologic activity in seizure‐generating sites or the wider recruited network. The objectives of CONTACTS are to extract and sequence coding and noncoding RNAs from explanted SEEG electrodes from patients with treatment-resistant epilepsy and then define gene expression and transcriptional states in seizure-onset zones and propagation areas. A multimodal predictive model will then be developed by integrating these features with clinical data including neurophysiologic signals to predict postoperative outcomes in epilepsy surgery. We will then prospectively evaluate the predictive value of surgical outcomes that incorporate the model.
CONTACTS combines inter-disciplinary collaboration between teams of scientists and clinicians informed and shaped by patient involvement that applies neurotechnology, molecular biology and data science to explore the human brain at high spatial resolution. These insights could stratify patients by predicted surgical outcomes, estimate seizure recurrence risk, and reveal new biomarkers or therapeutic targets. By leveraging unique biospecimens and advanced methods, the project’s impact will be to uncover disease mechanisms, improve prognostic tools, and inform future interventions for better epilepsy management.
