Association of Sleep Spindle Rate With Memory Consolidation in Children With Rolandic Epilepsy.

Abstract

Rolandic epilepsy (RE), the most common childhood focal epilepsy syndrome, is characterized by a transient period of sleep-activated epileptiform activity in the centrotemporal regions and variable cognitive deficits. Sleep spindles are prominent thalamocortical brain oscillations during sleep that have been mechanistically linked to sleep-dependent memory consolidation in animal models and healthy controls. Sleep spindles are decreased in RE and related sleep-activated epileptic encephalopathies. To further evaluate the association between this electrographic biomarker and cognitive dysfunction in this common disease, we investigate whether children with RE have deficient sleep-dependent memory consolidation and whether impaired memory consolidation is associated with reduced sleep spindles in the centrotemporal regions. In this prospective case-control study, children were trained and tested on a validated probe of memory consolidation, the motor sequence task (MST). Sleep spindles were measured from high-density EEG during a 90-minute nap opportunity between MST training and testing using an automated sleep spindle detector validated for use in children with and without epilepsy. Twenty-three children with RE (9 with active disease, 5F, age 6.9-12.8 years; 14 with resolved disease, 8F, age 8.8-17.8 years) and 19 age-matched and sex-matched controls (8F, age 6.9-18.7 years) were enrolled. Children with active epilepsy had decreased memory consolidation compared with control children (<i>p</i> = 0.001, mean percentage reduction 25.7%, 95% CI 10.3%-41.2%) and compared with children with resolved epilepsy (<i>p</i> = 0.007, mean percentage reduction 21.9%, 95% CI 6.2%-37.6%). Children with active epilepsy had decreased sleep spindle rates in the centrotemporal region compared with controls (<i>p</i> = 0.008, mean decrease 2.5 spindles per minute, 95% CI 0.7-4.4 spindles per minute). Spindle rate, but not spike rate or spike-wave index, correlated with sleep-dependent memory consolidation (<i>p</i> = 0.004, mean MST improvement of 3.9%, 95% CI 1.3%-6.4%, for each unit increase in spindles per minute). Children with RE have impaired sleep-dependent memory consolidation during the active period of disease that correlates with a deficit in the sleep spindle rate. This finding identifies a noninvasive biomarker to aid diagnosis and a potential etiologic mechanism to guide therapeutic discovery of cognitive dysfunction in RE and related sleep-activated epilepsy syndromes.