Abstract
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy syndrome, characterized by sleep-activated epileptiform spikes and seizures and cognitive deficits in school age children. Recent evidence suggests that this disease may be caused by disruptions to the Rolandic thalamocortical circuit, resulting in both an abundance of epileptiform spikes and a paucity of sleep spindles in the Rolandic cortex during non-rapid eye movement sleep (NREM); electrographic features linked to seizures and cognitive symptoms, respectively. The neuronal mechanisms that support the competitive shared thalamocortical circuitry between pathological epileptiform spikes and physiological sleep spindles are not well-understood. In this study we introduce a computational thalamocortical model for the sleep-activated epileptiform spikes observed in RE. The cellular and neuronal circuits of this model incorporate recent experimental observations in RE, and replicate the electrophysiological features of RE. Using this model, we demonstrate that: (1) epileptiform spikes can be triggered and promoted by either a reduced NMDA current or h-type current; and (2) changes in inhibitory transmission in the thalamic reticular nucleus mediates an antagonistic dynamic between epileptiform spikes and spindles. This work provides the first computational model that both recapitulates electrophysiological features and provides a mechanistic explanation for the thalamocortical switch between the pathological and physiological electrophysiological rhythms observed during NREM sleep in this common epileptic encephalopathy.
Highlights
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy, characterized by a transient period of spontaneous seizures and cognitive deficits in school age children
A Neural Mass Model of Rolandic Epilepsy (RE-Neural mass models (NMMs)) We introduce a new computational model RE-NMM based on the Costa NMM updated with features to reflect the somatosensory thalamocortical circuit and recent genetic findings in RE
We find that a range of dynamical spike activities in the RE-NMM emerge by varying the values of μ and gh respectively
Summary
Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy, characterized by a transient period of spontaneous seizures and cognitive deficits in school age children. We introduce a new neural mass model for Rolandic epilepsy (RE-NMM) incorporating the thalamocortical circuit underlying spikes and spindles in recent human and rodent studies (Clementeperez et al, 2017; Kramer et al, 2021) and genetic findings in RE (Lemke et al, 2013; Xiong and Zhou, 2017). This work provides a new computational model to better study RE and related sleepactivated epilepsies and proposes testable hypotheses of the neuronal mechanisms underlying this common disease
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