Abstracts

Rationale: Sleep spindles, bursts of 9 to 15 Hz “sigma band" oscillations during N2 sleep, are a key mechanism required for sleep-dependent memory consolidation. We have previously shown that children with Rolandic epilepsy (RE, also called self-limited epilepsy with centrotemporal spikes, SeLECTS), a common focal developmental epilepsy with variable severity of comorbid cognitive symptoms, have a focal spindle deficit in the region of sleep-potentiated interictal epileptiform discharges (IED). We hypothesized that the focal Rolandic spindle deficit would correspond to reduced sleep-dependent memory consolidation of a procedural motor task in RE compared to controls._x000D_
Methods: We recruited 17 children with RE, including 5 with active disease (defined as seizure within 12 months), 12 in disease resolution (seizure-free for > 12 months), and 16 age-matched controls. Subjects were trained on a motor sequence task (MST), given a 90-minute nap opportunity recorded with high-density EEG, and then tested on the same MST. High-resolution MRI was collected on the same day (Figure 1). For the MST, subjects were asked to repeat a 5-element tapping for 12 to 30s trials each separated by 30s of rest. Sleep-dependent memory consolidation was calculated as the percentage difference between the performance on the last 3 trials before sleep compared to the first three trials after awakening. Subjects who did not sleep were treated as within group wake controls (n=1, n=3, n=3). EEG source activity during N2 sleep was estimated using digitized headpoints to co-register to the MRI and the dSPM algorithm in MNE. Spindle activity in the inferior Rolandic cortex was estimated using an automated spindle detector. To test for sleep-dependent memory consolidation within each group, one-sampled t-test against a null hypothesis of zero and two-sampled t-tests compared to wake controls were used. Differences in spindle rate and memory consolidation, and their relationship, were evaluated between groups using mixed-effect generalized linear models._x000D_  _x000D_ Results: Children with active RE (red, p=0.3 vs. null hypothesis, p=0.26 vs. wake controls) have decreased sleep-dependent memory consolidation compared to controls (green, p=0.002 vs. null hypothesis, p=0.03 compared to wake) and children with resolved RE (blue, p=0.003 vs. null hypothesis, p=0.0008 vs. wake controls, (Figure 2A-B). Children with active RE have reduced spindles in the inferior Rolandic cortex compared to controls (p=0.03, Figure 2C). Spindle rate in the inferior Rolandic cortex positively correlates with sleep dependent memory consolidation in the combined groups (p=0.01, Figure 2D)._x000D_  _x000D_ Conclusions: We replicate our prior findings that children with active RE have a focal sleep spindle deficit in the inferior Rolandic cortex compared to controls. Our preliminary findings suggest that this spindle deficit corresponds to a disruption in sleep-dependent memory consolidation. Future work will add further subjects to test this mechanism of cognitive dysfunction in epileptic encephalopathies characterized by sleep-potentiated IEDs._x000D_
Funding: NIH NINDS R01NS115868