Spike‐wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity

Abstract

Key points The major electrophysiological hallmarks of absence seizures are spike and wave discharges (SWDs), consisting of a sharp spike component and a slow wave component. In a widely accepted scheme, these components are functionally coupled and reflect an iterative progression of neuronal excitation during the spike and post‐excitatory silence during the wave. In a genetic rat model of absence epilepsy, local pharmacological inhibition of the centromedian thalamus (CM) selectively suppressed the spike component, leaving self‐contained waves in epidural recordings. Thalamic inputs induced activity in cortical microcircuits underlying the spike component, while intracortical oscillations generated the wave component. Based on these findings, we propose a model in which oscillatory waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of a synchronized SWD. Abstract Spike and wave discharges (SWDs) are the electrographic hallmark of absence seizures and the major diagnostic criterion for childhood absence epilepsy (CAE). In a widely accepted scheme, the alternating sequence of spikes and waves reflects an iterative progression of neuronal excitation during the spike component and post‐excitatory silence during the wave component. Here we challenge this view by showing that these two components are not necessarily coupled. In a genetic rat model of CAE, self‐contained waves occurred in motor cortex in synchrony with SWDs in the somatosensory system during blockade of afferent input from the thalamus. Current‐source density analyses of multi‐site local field potentials (LFPs) revealed layer‐specific activity, in which thalamic inputs induced a sequence of cellular‐synaptic events underlying the spike component, while intracortical oscillations generated the wave component. These findings indicate novel principles of SWDs, where oscillatory cortical waves provide adequate time windows for integration of thalamocortical inputs and feedback responses during generation of seizure activity.

On the Yin and Yang of spike and waves

“…In this issue of The Journal of Physiology , Terlau et al . (2020) (and many references therein) confirmed the Yin and Yang of SWDs in the GAERS model as recorded with silicon probes by showing increased multi‐unit activity during the spike of the spike‐wave complex at the site of origin, the facial area of the somatosensory cortex (S1), followed by neuronal silence. Moreover, they identified both cortical layer specific sinks during the spike and sources during the wave, illustrating that interlaminar processes in all cortical layers play a role in the occurrence of SWDs.…”

“…This results as described by Terlau et al . (2020) are important and interesting for several reasons. The fact that the wave remained untouched and that the spike vanished shows an obvious dissociation between the spike and the wave, and this has never been so clearly experimentally demonstrated.…”

“…1, Terlau et al . 2020). Another example comes from topographical studies in WAG/Rij rats – at the occipital cortex the wave is very prominent and the spike is lacking (Meeren et al .…”

“…The experiments reported by Terlau et al . (2020) used anaesthetized animals and considering the role of CM in attention and arousal, it is obvious that anaesthesia hampers the normal functioning of the CM. Moreover, general anaesthesia is known to reduce thalamo‐cortical and cortico‐cortical communication, but it is less clear whether the communication between different parts of the cortex is changed to the same extent as between cortex and thalamus and vice versa.…”

Dynamical mesoscale model of absence seizures in genetic models

“…Our model does not differ between GABA(A) and GABA(B) currents (the model of an individual node is not detailed enough for this), therefore our model cannot be used to investigate the contribution of these conductances which could play a role in the difference in frequency between rodents and people. Many different cortical cell layers interact differently during spike and waves as was established in GAERS [ 73 ], others showed preictal intracortical processes in WAG/Rij rats [ 74 ]. Future models might indeed require different populations of cells in different cortical layers, also since it was found that the superficial layers of the somatosensory cortex are indispensable for the occurrence of SWDs, while the deeper layers communicate directly with the thalamus [ 75 ].…”