Rationale: The retrosplenial cortex (RSC) is a brain region highly interconnected with several brain regions relevant to temporal lobe epilepsy (TLE). This cortex has been reported to be involved in seizure propagation, being sensitive to neuronal loss, structural alterations, and synaptic reorganization due to seizures. For this reason, RSC has been proposed as a potential hub between cortical and subcortical regions in epilepsy. Therefore, we aimed to determine the changes in neuronal activity patterns of this structure in the transition from focal to propagated seizures in the brain.
Methods: Focal-onset seizures were induced by hippocampal electrical stimulation in awake rats (n=5), while the local field potential (LFP) in the RSC, hippocampus (HIP), and orbitofrontal cortex (ORB) was recorded simultaneously.
Electrophysiological data and the Racine scale were used to classify seizures as low, medium, or high severity. Changes in power in the delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), and beta (12-35 Hz) frequency bands were analyzed during the baseline, ictal, post-ictal, and recovery periods. The coherence between the HIP-ORB, HIP-RSC, and RSC-ORB LFP signals was also assessed.Results: During the ictal period, only HIP beta power increased for low-severity seizures (n=13). For medium-severity seizures (n=18), this power increase was cross-sectional for all bands in HIP, RSC, and ORB. In contrast, for high-severity seizures (n=17), only delta power in the ORB was unaltered compared to baseline. As for the post-ictal period, low-severity seizures showed a generalized suppression of activity below baseline in all frequencies and brain regions. This was also observed in the HIP for medium-severity seizures. For high-severity seizures, the post-ictal suppression was observed in the HIP and ORB for the beta band. In the case of low-severity seizures, post-ictal suppression was sustained during the recovery period in the ORB.
The mean coherence between the HIP-RSC during the ictal period was inversely related to seizure severity for delta and theta bands. Conversely, the mean coherence between the HIP-ORB during the same period was directly related to seizures severity for theta, alpha and beta bands.Conclusions: Our results allowed us to characterize the severity of temporal lobe seizures according to electrophysiological features at different brain regions. The changes in the temporal coordination of low-frequency oscillations suggest that the grade of coherence between the HIP-RSC might play a relevant role. This work will contribute to understanding how the RSC may coordinate focal-onset seizures and propose new targets for circuit-based therapeutic interventions.
Funding: This work was supported by Project Grant ACE210007 (Biomedical Neuroscience Institute, BNI, 2018-2022); The Pew Charitable Trusts: The Pew Innovation Fund Grant #34503 and Beca ANID de Doctorado Nacional 21200302.