Behavioral unresponsiveness and impaired auditory event-related potentials in the anterior insula during rat absence seizures

Absence epilepsy is marked by sudden lapses in consciousness accompanied by spike–wave discharges (SWDs), yet the neural mechanisms underlying impaired sensorimotor processing in these episodes remain unresolved. Prior work has shown that normal-appearing signals can persist in primary sensory cortical areas during seizures, suggesting that impaired behavioral responsiveness may arise from disruptions in higher-order association cortex. To investigate this hypothesis, we combined behavioral testing with simultaneous local field potential recordings in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Rats were trained in an auditory conditioned response task, allowing comparison of tone-evoked responses during interictal baseline and ictal SWDs. We found that behavioral performance collapsed during SWDs, with correct responses falling from ∼88% at baseline to <1% during SWDs (p < 0.001). Nevertheless, auditory event-related potentials in primary auditory cortex (Au1) during SWDs were not significantly decreased. In contrast, we identified a novel oscillatory evoked potential in the anterior insular cortex (AIC) that was robust in controls, attenuated in GAERS at baseline, and markedly reduced during SWDs. Notably, reductions in AIC response magnitude also occurred during satiated, unmotivated states, but waveform structure was preserved, distinguishing motivational modulation from seizure-related disruption. These results demonstrate that absence seizures selectively impair signals in the anterior insula rather than in primary auditory cortex, identifying the AIC as a potentially critical hub for gating auditory conscious awareness. Beyond refining models of seizure-related unconsciousness, the discovery of an insular oscillatory potential highlights a candidate biomarker and intervention target for absence epilepsy, with broader implications for understanding impaired consciousness in anesthesia, sleep, and brain injury.