Ictal-Related Chirp as a Biomarker for Monitoring Seizure Progression

AbstractDespite being prevalent, the causes, mechanisms, and progression of epilepsy—a chronic neurological disorder with unprovoked seizures—are not well understood, complicating drug development for treatment. This study used a comprehensive mouse epilepsy kindling model dataset to investigate frequency modulation (chirp) as a potential indicator of distinct states of epilepsy (early evoked discharge, late evoked discharge, spontaneous recurrent seizure, and drug state). Employing time-frequency ridge extraction, chirp identification, and statistical testing, our analyses revealed that chirp patterns occur in the majority of ictal discharges (>81.6%), persisting across evoked and spontaneous seizures. While the focus was on hippocampal recordings, chirps were also detected in the piriform peripheral cortex. Significant frequency and duration changes in chirp patterns during the transition from early to late evoked ictal events suggest their potential as the screening tool for seizure progression. Additionally, detailed analyses illuminate the impact of Lorazepam, aGABAAenhancer, on chirp characteristics, providing insights into how increased inhibitory tone quantifiably influences excitatory-inhibitory balances during seizures.