Spectral and coupling characteristics of somatosensory cortex and centromedian thalamus differentiate between pre- and inter-ictal 5-9 Hz oscillations in a genetic rat model of absence epilepsy

Abstract

Spike-wave-discharges (SWD) are the electrophysiological hallmark of absence epilepsy. SWD are generated in the thalamo-cortical network and a seizure onset zone was identified in the somatosensory cortex (S1). We have shown before that inhibition of the centromedian thalamic nucleus (CM) in GAERS rats resulted in a selective suppression of the spike component while rhythmic cortical 5-9 Hz oscillations remained present. Such oscillations are often seen to precede SWD activity in this well-validated genetic rat model of absence epilepsy, but are also seen in seizure-free periods. The present study characterizes the profile of 5-9 Hz oscillations in thalamo-cortical circuits during pre- and inter-ictal states. Here we recorded local-field-potentials in S1, CM and the secondary motor cortex of GAERS. Time-frequency analysis was used to assess spectral power and non-linear-association analysis was used to determine coupling strength and directionality between brain areas. Phase-specific electrical stimulation was used to compare cortical excitability and to assess the risk for epileptic afterdischarges. Coupling strength and spectral power were higher for the inter-ictal compared to the pre-ictal 5-9 Hz oscillations. However, coupling strength during pre-ictal oscillations was higher than during passive wakefulness. Double pulse stimulation during 5-9 Hz oscillations was more likely to induce epileptic afterdischarges compared to stimulation during passive wakefulness. While no overall differences in cortical excitability were revealed, phase-specific differences in excitability were noticed during the oscillation. Our findings indicate that intermediate coupling between S1 and CM favors SWD generation, thereby adding to the previous notion that 5-9 Hz oscillations represent high-risk periods for seizure generation. In general, pre-ictal oscillations display a unique electrophysiological profile in GAERS that might pave the way for qualification as biomarker for SWD generation and seizure prediction.

Keywords: Afterdischarges; Centromedian thalamus; Evoked potentials; Excitability; GAERS; Network analysis; Somatosensory cortex; Spike and wave discharges.