BEHAVIORAL AND SPECTRAL EEG BIOMARKERS OF EPILEPTOGENESIS AND PHARMACORESISTANCE IN A LONGITUDINAL PILOCARPINE MODEL OF TEMPORAL LOBE EPILEPSY

Temporal lobe epilepsy (TLE) is a progressive disorder characterized by dynamic alterations in neural networks, behavior, and responsiveness to antiepileptic drugs, though integrated longitudinal studies are still limited. Here, we investigated behavioral and electrocorticographic (EcoG) changes across TLE progression and their correlation using a pilocarpine-induced rat model. Behavioral and EcoG recordings were collected at five time points: baseline (T0), acute phase (T1, 1 week post–status epilepticus), latent phase (T2, 4 weeks), chronic phase (T3, 8 weeks), and after assessment of phenobarbital responsiveness (T4, 12 weeks), allowing discrimination between drug-responsive and drug-resistant animals. Our results revealed progressive, phase-specific alterations. From the acute to the chronic phase, epileptic rats developed a hypermotor phenotype, marked by increased exploratory activity and reduced immobility, together with reduced anxiety-like behavior in the light–dark test. In parallel, natural behaviors progressively deteriorated, as evidenced by decreased burrowing activity and the emergence of depressive-like anhedonia. During the chronic phase, significant cognitive impairment emerged in the novel object recognition test. EcoG analysis revealed dynamic modulation of spectral power across frequency bands, which significantly correlated with behavioral outcomes. Furthermore, a distinct pharmacoresistant subpopulation emerged, characterized by a coherent phenotype with specific functional signatures. Overall, this study provides a comprehensive longitudinal framework for TLE progression and identifies potential translational biomarkers relevant for epileptogenesis and antiepileptic drug resistance.