Termination of ongoing spike-wave discharges investigated by cortico-thalamic network analyses

Abstract

Purpose: While decades of research were devoted to study generation mechanisms of spontaneous spike and wave discharges (SWD), little attention has been paid to network mechanisms associated with the spontaneous termination of SWD. In the current study coupling-dynamics at the onset and termination of SWD were studied in an extended part of the cortico-thalamo-cortical system of freely moving, genetic absence epileptic WAG/Rij rats.

Methods: Local-field potential recordings of 16 male WAG/Rij rats, equipped with multiple electrodes targeting layer 4 to 6 of the somatosensory-cortex (ctx4, ctx5, ctx6), rostral and caudal reticular thalamic nucleus (rRTN & cRTN), ventral postero medial (VPM), anterior- (ATN) and posterior (Po) thalamic nucleus, were obtained. Six seconds lasting pre-SWD->SWD, SWD->post SWD and control periods were analyzed with time-frequency methods, and between-region interactions were quantified with frequency-resolved Granger Causality (GC) analysis.

Results: Most channel pairs showed increases in GC lasting from onset to offset of the SWD. While for most thalamo-thalamic pairs a dominant coupling direction was found during the complete SWD, most cortico-thalamic pairs only showed a dominant directional drive (always from cortex to thalamus) during the first 500ms of SWD. Channel pair ctx4-rRTN showed a longer lasting dominant cortical drive, which stopped 1.5sec prior to SWD offset. This early decrease in directional coupling was followed by an increase in directional coupling from cRTN to rRTN 1sec prior to SWD offset. For channel pairs ctx5-Po and ctx6-Po the heightened cortex->thalamus coupling remained until 1.5sec following SWD offset, while the thalamus->cortex coupling for these pairs stopped at SWD offset.

Conclusion: The high directional coupling from somatosensory cortex to the thalamus at SWD onset is in good agreement with the idea of a cortical epileptic focus that initiates and entrains other brain structures into seizure activity. The decrease of cortex to rRTN coupling as well as the increased coupling from cRTN to rRTN preceding SWD termination demonstrates that SWD termination is a gradual process that involves both cortico-thalamic as well as intrathalamic processes. The rostral RTN seems to be an important resonator for SWD and relevant for maintenance, while the cRTN might inhibit this oscillation. The somatosensory cortex seems to attempt to reinitiate SWD following its offset via its strong coupling to the posterior thalamus.