PT - JOURNAL ARTICLE AU - Mirjebreili, Morteza AU - Martinez de Aguirre Ibarreta, Josu AU - Marinazzo, Daniele AU - Chauvière, Laetitia TI - High-Order Information Analysis of Epileptogenesis in the Pilocarpine Rat Model of Temporal Lobe Epilepsy AID - 10.1523/ENEURO.0403-24.2025 DP - 2025 May 01 TA - eneuro PG - ENEURO.0403-24.2025 VI - 12 IP - 5 4099 - http://www.eneuro.org/content/12/5/ENEURO.0403-24.2025.short 4100 - http://www.eneuro.org/content/12/5/ENEURO.0403-24.2025.full SO - eNeuro2025 May 01; 12 AB - Temporal lobe epilepsy (TLE) is a devastating disease, often pharmacoresistant and with a high prevalence of 1% worldwide. There are a few disease-modifying therapies; thus, prevention has become a health priority. The overarching goal of this research project is to highlight the system's dynamics at different stages before TLE onset to identify an early shift in network dynamics trajectory toward disease onset. Researchers often investigate collective brain activity by tracking dynamical interactions of the signal recorded at multiple sites. However, these interactions are usually only computed between pairs of brain regions, at the risk of missing simultaneous interactions of three or more areas, an aspect that is crucial in a networked disease such as TLE. We thus propose to track, on a rich dataset of electrophysiological brain signals recorded within the temporal lobe (TL) of adult male Wistar Han rats, the formation and dissolution of high-order informational multiplets in time during distinct natural behaviors in an animal model of TLE. We identified the informational content of the multiplets as synergistic or redundant. Results identified an early transition of synergistic and redundant multiplets ahead of TLE onset with the predominant involvement of four TL brain regions in generating theta (4–12 Hz) activity. This shift has been shown predominantly during exploration, a theta-dependent behavior, less during rest and sleep. This specific change suggests a shift in communication from an integrated to a segregated network toward TLE onset.