Lateral asymmetry of early seizure manifestations in experimental generalized epilepsy

Reorganization of seizure networks during epileptogenesis involves cortico-subcortical and interhemispheric interactions. In the audiogenic kindling (AK) model of generalized tonic–clonic seizures, upstream seizure propagation along ascending brainstem-to-forebrain pathways determines progressive intensification of repeated sound-induced convulsions. Full-blown audiogenic seizures are bilaterally symmetric and their repetition results in bisynchronous recruiting the cortex in secondary epileptogenesis. The present study describes lateral asymmetry of initial behavioral and EEG manifestations of audiogenic seizures and AK in Wistar and WAG/Rij rats with acoustic hypersensitivity. These rats exhibit consistent individual lateralization of running seizures (run directionality) induced by repeated binaural stimulation. Since this initial preconvulsive running reflects seizure onset in the auditory brainstem, the running asymmetry suggests non-symmetric early epileptic activation of brainstem substrates by sound in these rats. Repetition of the asymmetric brainstem seizures led to asynchronous recruiting the cortex into seizure network and lateralization of running seizures was predictive for asymmetry of early cortical seizure manifestations in Wistar and WAG/Rij rats. Both electrographic markers of AK, spreading depression (SD) and post-running afterdischarge, first appeared in the cortex ipsilateral to run direction, suggesting lateralized brainstem-to-forebrain seizure generalization during AK. At the population level, no bias in lateralization of running and SD was found in Wistar and WAG/Rij rats but incidence of secondary cortical seizures varied, depending on strain and run laterality. Among Wistar rats, cortical seizures developed more rarely in right-runners than in left-runners, suggesting enhanced resistance of the right hemisphere to epileptogenesis in rats of this strain. WAG/Rij rats with mixed (absence and audiogenic) epilepsy showed weak lateralization of early cortical seizures and no left–right difference in their incidence during AK. Present findings suggest (1) lateralized brainstem-to-forebrain seizure propagation and hemispheric difference in its facility in Wistar rats, (2) alterations of intra- and interhemispheric seizure propagation in WAG/Rij rats with genetic absence epilepsy.

► Wistar and WAG/Rij rats exhibit stable individual asymmetry of audiogenic running.
► Repetition of these brainstem seizures evokes asymmetric activation of the cortex.
► Cortical asymmetry implies lateralized brainstem-to-forebrain seizure spread.
► Wistar rats exhibit reduced epileptogenicity of the right hemisphere.
► Interhemispheric seizure spread is altered in WAG/Rij rats with absence seizures.