Prolongation of cortical sleep spindles during hippocampal interictal epileptiform discharges in epilepsy patients

Abstract

Objective: Memory deficits are frequent among patients with epilepsies affecting the temporal lobe. Hippocampal interictal epileptic discharges (hIEDs), the presumed epileptic exaggeration of sharp wave-ripples (SWRs), are known to contribute to memory dysfunction, but the potential underlying mechanism is unknown.The precise temporal coordination between hippocampal SWRs and corticothalamic spindles during sleep is critical for memory consolidation. Moreover, previous investigation indicated that hIEDs induce neocortical spindlelike oscillation.In the present study, we aimed to assess the influence of hIEDs on neocortical spindles. Methods:We analyzed the spindle characteristics (duration, amplitude, frequency) of 21 epilepsy patients implanted with foramen ovale (FO) electrodes during a whole night sleep. Scalp sleep spindles were categorized based on their temporal relationship to hIEDs detected on the FO electrodes. Three groups were created: (1) spindles coinciding with hIEDs, (2) spindles "induced" by hIEDs, and(3) spindles without hIED co-occurrence. Results:We found that spindles co-occurring with hIEDs had altered characteristics in all measured properties, lasted longer by 126 ± 48 ms (mean ± SD), and had higher amplitude by 3.4 ± 3.2 μV, and their frequency range shifted toward the higher frequencies within the 13-15-Hz range. Also, hIED-induced spindles had identical oscillatory properties to spindles without any temporal relationships with hIEDs. In more than half of our subjects, clear temporal coherence was revealed between hIEDs and spindles, but the direction of the coupling was patient-specific. Significance:We investigated the effect of hippocampal IEDs on neocortical spindle activity and found spindle alterations in cases of spindle-hIED cooccurrence, but not in cases of hIED-initiated spindles. We propose that this is a marker of a pathologic process, where IEDs may have direct effect on spindle generation. It could mark a potential mechanism whereby IEDs disrupt memory | 2257 SÁKOVICS et al.

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

“…However, spindle duration was significantly lower in TLE compared with NEC, and although the significance of this is unclear in this study, this change could affect spindle function and has been reported previously in a separate epilepsy cohort. 39 Somewhat surprisingly, we found no significant associations between hIED activity and sleep measures in TLE, including sleep structure, spindle density, or spindle-SO coupling. Similar to previous studies, 17 we observed significant hIED-to-spindle coupling, with hIEDs preferentially occurring within 1 second before spindle onset.…”

Sleep, oscillations, and epilepsy

“…Beyond intrinsic spatial features of epileptic activity, these discharges have also been associated with changes to the spatiotemporal properties of sleep oscillations. Spindles that co‐occur with interictal discharges were found to have a longer duration, higher amplitude, and higher frequency compared to isolated spindles 53 . Furthermore, brain regions that exhibit strong coupling of their local spindle oscillations to remote interictal discharges can generate spindles with a larger spatial extent and a higher propensity to travel compared to brain regions without such interictal discharge‐coordinated activity 54 .…”

“…Interictal discharges, especially those in medial temporal regions, can be associated with resetting the slow oscillation phase and time-locked spindle oscillation (Figure 2B,D). 47,53,54 Such interactions are located in brain regions remote from the location of the interictal discharge, suggesting a hijacking of sleep networks aimed at large-scale communication and local disruption of sleep architecture (Figure 2C). 54,55 Functional neuroimaging also supports wide-ranging alterations in networks around the time of interictal activity during wakefulness, with vulnerability to such changes associated with poorer neurocognitive status.…”

“…Spindles that co-occur with interictal discharges were found to have a longer duration, higher amplitude, and higher frequency compared to isolated spindles. 53 Furthermore, brain regions that exhibit strong coupling of their local spindle oscillations to remote interictal discharges can generate spindles with a larger spatial extent and a higher propensity to travel compared to brain regions without such interictal discharge-coordinated activity. 54 Thus, it is possible that chronic expression of epileptic patterns could even shape the ability of the cortex to participate in physiologic sleep oscillations.…”

Human thalamic recordings reveal that epileptic spikes block sleep spindle production during non-rapid eye movement sleep

“…Epileptic spikes have been proposed to hijack the circuitry that produces spindles and thereby disrupt sleep-dependent memory consolidation (Beenhakker & Huguenard, 2009;Kramer et al, 2021). However, competing observations suggest that epileptic spikes precedeand therefore may induce -sleep spindles, with potentially pathologic consequences for cognitive function (Dahal et al, 2019;Gelinas et al, 2016;Sákovics et al, 2022). How and whether cortical spikes interact and interfere with thalamic sleep spindles in humans is unknown.…”