Focal epilepsy disrupts spindle structure and function

Abstract

Sleep spindles are the hallmark of N2 sleep and are attributed a key role in cognition. Little is known about the impact of epilepsy on sleep oscillations underlying sleep-related functions. This study assessed changes in the global spindle rate in patients with epilepsy, analysed the distribution of spindles in relation to the epileptic focus, and performed correlations with neurocognitive function. Twenty-one patients with drug-resistant focal epilepsy (12 females; mean age 32.6 ± 10.7 years [mean ± SD]) and 12 healthy controls (3 females; 24.5 ± 3.3 years) underwent combined whole-night high-density electroencephalography and polysomnography. Global spindle rates during N2 were lower in epilepsy patients compared to controls (mean = 5.78/min ± 0.72 vs. 6.49/min ± 0.71, p = 0.02, d = − 0.70). Within epilepsy patients, spindle rates were lower in the region of the epileptic focus compared to the contralateral region (median = 4.77/min [range 2.53–6.18] vs. 5.26/min [2.53–6.56], p = 0.02, rank biserial correlation RC = − 0.57). This decrease was driven by fast spindles (12–16 Hz) (1.50/min [0.62–4.08] vs. 1.65/min [0.51–4.28], p = 0.002, RC = − 0.76). The focal reduction in spindles was negatively correlated with two scales of attention (r = − 0.54, p = 0.01; r = − 0.51, p = 0.025). Patients with focal epilepsy show a reduction in global and local spindle rates dependent on the region of the epileptic focus. This may play a role in impaired cognitive functioning. Future work will show if the local reduction in spindles can be used as potential marker of the epileptic focus.

Altered Sleep Microarchitecture and Cognitive Impairment in Patients With Temporal Lobe Epilepsy

“…Other human studies on spindles in epilepsy have been limited to smaller sample sizes of 10–20 patients. 28,39,45 Conducting this analysis in a larger sample was made possible by leveraging recently validated automated deep learning algorithms to label sleep stages and hIEDs across thousands of hours of EEG data. This is the first study of such magnitude focusing exclusively on adult TLE, the most common focal epilepsy disorder, which establishes a robust effect on spindle density linked to the ipsilateral epileptic network and to cognitive impairment.…”

Sleep, oscillations, and epilepsy

“…It will be particularly interesting to continue investigating whether all the correlations described above (e.g., interictal spikes and spindles) also depend upon the time during the night and day cycle. 66 AUTHOR CONTRIBUTIONS Christophe Bernard: Writing-review and editing (equal). Birgit Frauscher: Writing-review and editing (equal).…”

“…Sleep architecture is very different between the beginning and the end of sleep. It will be particularly interesting to continue investigating whether all the correlations described above (e.g., interictal spikes and spindles) also depend upon the time during the night and day cycle 66 …”

“…The overall spindle rate is reduced in adults with focal epilepsy and children with self-limited childhood epilepsy with centrotemporal spikes, with a focal reduction at the site of the epileptic focus that correlates with impaired cognitive functioning such as reduced attention and verbal memory performance. 55,66 The effects can be widespread; hippocampal epileptic activity is associated with a disruption of sleep spindle generation in remote cortical areas. 54 Sleep slow waves show both widespread and local increase at the site of the epileptic focus, 67 in keeping with the finding that epileptic activity is enhanced during slow oscillations and not NREM sleep itself.…”

“…In addition to sleep macro‐ and microstructure alterations, epileptic activity is associated with modifications of typical sleep oscillations such as slow waves, sleep spindles, and REM sleep sawtooth waves. The overall spindle rate is reduced in adults with focal epilepsy and children with self‐limited childhood epilepsy with centrotemporal spikes, with a focal reduction at the site of the epileptic focus that correlates with impaired cognitive functioning such as reduced attention and verbal memory performance 55,66 . The effects can be widespread; hippocampal epileptic activity is associated with a disruption of sleep spindle generation in remote cortical areas 54 .…”