Spike-spindle coupling during sleep and its mechanism explanation in childhood focal epilepsy

Abstract

Childhood focal epilepsy (CFE) is a serious neurological disorder characterized by epileptic seizures arising from a focal or multi-focal zone of the brain in clinics. During non-rapid eye movement (NREM) sleep stage, epileptiform discharges become frequent, and sleep spindles are generated through local interaction between thalamic neurons for CFE patients. Recent research has shown that epileptiform spikes significantly induce spindle oscillations within 1 s (say, spike-spindle coupling) during NREM sleep in focal epilepsy, which might damage cognitive function of epilepsy patients. However, the temporal interaction mechanism between spikes and spindles is lack of understanding. In this paper, we first develop a new thalamocortical model of CFE (CFE-TCM) by integrating M-type potassium current, persistent sodium current and NMDAR current into Costa model, where the three types of currents are important for modulating the excitability of thalamocortical system. Then we demonstrate in simulations that: (1) the temporal spike-spindle coupling oscillatory patterns do exist in real CFE-EEGs recorded in clinics; (2) the constructed model CFE-TCM has a capacity of generating spike-spindle coupling discharges, and the corresponding statistical results are consistent with those obtained from real EEGs; (3) the spike-spindle coupling discharges are mediated by the strength of long-range thalamus-cortex connections where the excitable projection from thalamocortical neuron in thalamus to pyramidal neuron in cortex takes a great role. The obtained results reveal that pathological spike-spindle coupling may be a potential marker of thalamocortical circuit dysfunction, which will provide a possible treatment strategy for disease progression and cognition impairment in focal epilepsy.

Keywords: Long-range thalamus-cortex connection; M-type potassium current; NMDAR current; Persistent sodium current; Spike-spindle coupling; Thalamocortical neural mass model.