EEG-fMRI in awake rat and whole-brain simulations show decreased brain responsiveness to sensory stimulations during absence seizures

Abstract

Absence seizures are characterized by regular and generalized spike-and-wave electrical patterns in the brain, resulting in unresponsiveness to environmental stimuli. In patients suffering absence epilepsy, recurring seizures can significantly decrease their quality of life and lead to yet untreatable comorbidities. The mechanism underlying the reduced responsiveness to external stimulus remains unknown. This study aimed to investigate whole-brain responsiveness to visual and somatosensory whisker stimulation in GAERS, a well-established rat model for absence epilepsy. Animals were imaged continuously using a quiet zero-echo-time functional magnetic resonance imaging (fMRI) sequence while in a non-curarized awake state, allowing for naturally occurring seizures to be produced inside the 9.4T magnet. Sensory stimulations were applied in 28 fMRI sessions during interictal and ictal periods, as assessed by concurrent EEG recordings, and 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 whole-brain responses to both sensory stimulations were suppressed and spatially hindered during a seizure. In several cortical regions, hemodynamic responses were negatively polarized during seizures, despite the application of a stimulus. The simulation results agreed well with fMRI findings, showing restricted propagation of spontaneous activity due to stimulation. These results suggest that typical information flow in functional pathways responsible for processing sensory stimulation is hindered and suppressed during absence seizures, potentially contributing to decreased responsiveness.