Persistence of Cortical Sensory Processing during Absence Seizures in Human and an Animal Model: Evidence from EEG and Intracellular Recordings

Mathilde Chipaux,Laurent Vercueil,Séverine Mahon,Stéphane Charpier,Anna Kaminska,Jean-Pierre Mothet

doi:10.1371/journal.pone.0058180

Abstract

Absence seizures are caused by brief periods of abnormal synchronized oscillations in the thalamocortical loops, resulting in widespread spike-and-wave discharges (SWDs) in the electroencephalogram (EEG). SWDs are concomitant with a complete or partial impairment of consciousness, notably expressed by an interruption of ongoing behaviour together with a lack of conscious perception of external stimuli. It is largely considered that the paroxysmal synchronizations during the epileptic episode transiently render the thalamocortical system incapable of transmitting primary sensory information to the cortex. Here, we examined in young patients and in the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), a well-established genetic model of absence epilepsy, how sensory inputs are processed in the related cortical areas during SWDs. In epileptic patients, visual event-related potentials (ERPs) were still present in the occipital EEG when the stimuli were delivered during seizures, with a significant increase in amplitude compared to interictal periods and a decrease in latency compared to that measured from non-epileptic subjects. Using simultaneous in vivo EEG and intracellular recordings from the primary somatosensory cortex of GAERS and non-epileptic rats, we found that ERPs and firing responses of related pyramidal neurons to whisker deflection were not significantly modified during SWDs. However, the intracellular subthreshold synaptic responses in somatosensory cortical neurons during seizures had larger amplitude compared to quiescent situations. These convergent findings from human patients and a rodent genetic model show the persistence of cortical responses to sensory stimulations during SWDs, indicating that the brain can still process external stimuli during absence seizures. They also demonstrate that the disruption of conscious perception during absences is not due to an obliteration of information transfer in the thalamocortical system. The possible mechanisms rendering the cortical operation ineffective for conscious perception are discussed, but their definite elucidation will require further investigations.

Highlights

The cardinal clinical symptom of absence epilepsy, which mostly occurs during childhood, is a transient impairment of consciousness [1,2,3,4]
Square air-puff stimuli were repeatedly applied on whiskers of non-epileptic rats and Genetic Absence Epilepsy Rats from Strasbourg (GAERS), in between and during seizures, with the minimal intensity to produce the largest wERP in absence of cortical paroxysmal activities (10–40 p.s.i., interictal period in GAERS; 10–50 p.s.i., control Wistar rats)
We examined how sensory inputs, generated by natural sensory stimuli, are processed by the cerebral cortex during absence seizures

Summary

Introduction

The cardinal clinical symptom of absence epilepsy, which mostly occurs during childhood, is a transient impairment of consciousness [1,2,3,4]. A cortical focal initiation of SWDs has been found in rodent genetic models, such as the Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and the WAG/Rij rats, which closely phenocopy the human absence seizures [13,14] In these two rat strains, SWDs are initiated from the facial somatosensory cortex [15,16,17,18,19], due to the hyperactivity and early paroxysmal discharges of the deep-layer pyramidal neurons [17,19,20]. Square air-puff stimuli were repeatedly applied on whiskers of non-epileptic rats and GAERS, in between and during seizures, with the minimal intensity to produce the largest wERP in absence of cortical paroxysmal activities (10–40 p.s.i., interictal period in GAERS; 10–50 p.s.i., control Wistar rats) Using this range of intensities, whisker stimulations did not interrupt the seizures (see Figure 4B1 right) and the stimulus-trigger averaging (.20 trials) of cortical EEG waves revealed a clear-cut wERP during SWDs (Figure 2C2).

Methods

Results

Conclusion