Authors :
Presenting Author: Katharina Schiller, PhD – Montreal Neurological Hospital and Institute
Nicolás von Ellenrieder, PhD – Montreal Neurological Hospital and Institute
Daniel Mansilla, MD – McGill University
Jean Gotman, PhD – Montreal Neurological Hospital and Institute
Birgit Frauscher, MD, PhD – Department of Neurology, Duke University School of Medicine, Durham, NC, USA
Rationale:
Neurocognitive deficits are common in temporal lobe epilepsy (TLE) (1). Recent studies in healthy controls showed a positive correlation between sleep spindles coupled to sleep slow waves and cognitive functioning (2, 3). We hypothesized that disturbed spindle-slow wave coupling could be an important factor contributing to neurocognitive deficits in TLE. Therefore, we aimed to determine local and global differences in spindle-slow wave coupling in patients with TLE in comparison to a healthy control group using combined high-density electroencephalography (HD-EEG) and polysomnography.
Methods: Twenty patients (12 female; 36.5 ± 9.9y) with unilateral drug-resistant TLE (10 left and 10 right; 15 mesiotemporal) and 20 age- and sex-matched healthy controls were included in this study. Overnight EEG recordings were sleep scored according to AASM criteria and all N2 and N3 epochs were selected. Spindles (10-16Hz; 0.5-2s) and slow waves (0.5-4Hz) were automatically detected using validated detectors and were visually cross-checked. Spikes were marked at the peak by an epileptologist. Detections of spindles and slow waves at time of a spike marking and slow wave detections with onset < 150ms after the peak of the spike were excluded. Coupling of spindles and slow waves was defined as any overlap of both detections.
Results: Coupled spindle-slow wave rates (per minute) during all N2 and N3 epochs were globally reduced in patients with TLE compared to healthy controls (patients vs. controls: median [range]: 0.18 [0.01; 0.65] vs. 0.35 [0.09; 0.98], non-parametric p=0.009, Cliff’s d=0.48). This reduction was also found in coupled fast spindles (12-16Hz)-slow waves (patients vs. controls: 0.06 [0.001; 0.35] vs. 0.18 [0.02; 0.46], p=0.006, d=0.46) and slow spindles (10-12Hz)-slow waves (patients vs. controls: 0.11 [0.01; 0.38] vs. 0.19 [0.04; 0.55], p=0.023, d=0.42) (
Figure 1). Within patients with TLE, there was no local difference between the coupling rates in the lobe with the epileptic focus (left or right temporal) compared to the contralateral side (epileptic focus vs. contralateral side: 0.08 [0.01; 0.29] vs. 0.05 [0.001; 0.18], p=0.135, d=0.065).
Conclusions:
Despite a focal epileptic generator, patients with TLE showed a widespread reduction of coupled spindle-slow wave rates. As coupling was found to be associated with neuropsychological performances in previous studies, this widespread reduction may contribute to mechanisms of poor cognitive functions in patients with TLE.
References:1. Samson S & Denos M. Neuropsychology of temporal lobe epilepsies. Handb Clin Neurol. 2022;187:519-29.
2. Hahn MA et al.. Slow oscillation-spindle coupling predicts enhanced memory formation from childhood to adolescence. Elife. 2020;9.
3. Baena D et al.. Spindle-slow wave coupling and problem-solving skills: Impact of age. Sleep. 2024.
Funding: This study was supported by a project grant of the Canadian Institutes of Health Research to BF (PJT-175056) and JG (FDN-143208). KS was funded by a postdoctoral fellowship by the German Research Foundation (507037359).