How Absence Seizures Impair Sensory Perception: Insights from Awake fMRI and Simulation Studies in Rats

In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. Absence seizures are characterized by spike-and-wave discharges on the electroencephalogram associated with a transient alteration of consciousness. However, it is still unknown how the brain responds to external stimuli during and outside of seizures.This study aimed to investigate responsiveness to visual and somatosensory stimulation in GAERS, a well-established rat model for absence epilepsy. Animals were maintained in a non-curarized awake state allowing for naturally occurring seizures to be produced inside the magnet. They were imaged continuously using a quiet zero-echo-time functional magnetic resonance imaging (fMRI) sequence. Sensory stimulations were applied during interictal and ictal periods. Whole brain responsiveness and hemodynamic responses were compared between these two states. Additionally, a mean-field simulation model was used to mechanistically explain the changes of neural responsiveness to visual stimulation between interictal and ictal states.Results showed that, during a seizure, whole-brain responses to both sensory stimulations were suppressed and spatially hindered. In several cortical regions, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The simulation experiments also showed restricted propagation of spontaneous activity due to stimulation and so agreed well with fMRI findings. These results suggest that sensory processing observed during an interictal state is hindered or even suppressed by the occurrence of an absence seizure, potentially contributing to decreased responsiveness during this absence epileptic process.