Thalamic engagement by epileptic spikes as a mechanism for widespread slow oscillation–spindle decoupling

Abstract

We read with great interest the recent article by Schiller and colleagues, “Widespread Decoupling of Spindles and Slow Waves in Temporal Lobe Epilepsy,”¹ and were struck by how their findings dovetail with our own observations. In our work “Thalamic Epileptic Spikes Disrupt Sleep Spindles in Patients With Epileptic Encephalopathy,”² we found that when a thalamic epileptic spike co-occurs with a cortical slow oscillation, thalamic spindle incidence is suppressed precisely during the phase at which spindles would ordinarily peak (see Figure 2D in Wodeyar et al.²), a clear decoupling of slow oscillations and spindles due to epileptic spikes in the thalamus. This phenomenon was not limited to epileptic encephalopathies, nor to a specific age range (patients were aged 9–55 years), suggesting that once an epileptic spike engages the thalamus, its disruptive influence on slow oscillation–spindle coupling could be global.

Employing high-density electroencephalography (EEG) and a comparison between healthy controls and patients with epilepsy, Schiller et al. now demonstrate that the slow oscillation–spindle disruption can indeed extend beyond focal epileptogenic sites in temporal lobe epilepsy, broadening our understanding of how local epileptic pathology can be linked to global network consequences. We note that the authors did not detect a direct relationship between epileptic spikes and the observed decoupling. Although efforts were made to exclude slow oscillations and spindles temporally linked to epileptic spikes, it is possible that epileptic spikes originating from deeper structures (such as the hippocampus in mesial temporal lobe epilepsy) were not fully captured in scalp EEG recordings.^{3, 4} Thus, consistent with our findings, one plausible explanation is that the association between epileptic spikes and slow oscillation–spindle coupling may critically depend on whether these spikes effectively propagate from the epileptogenic area to thalamus. If epileptic spike rates are high but only limitedly reach the thalamus, the global decoupling effect could be diminished, possibly explaining the lack of correlation in Schiller et al.'s cohort. Supporting this interpretation, the observed correlations between spike rates and slow oscillation–spindle coupling rates in their study, although not statistically significant, were consistently negative in both N2 and N3 sleep.

Altogether, these results reinforce the hypothesis that diverse epilepsies may share a common neurophysiological mechanism involving disrupted normal coordination of slow oscillations and spindles, with potentially significant implications for overnight memory consolidation.⁵ We look forward to future studies delineating the conditions under which epileptic spikes propagate to the thalamus, the extent of their downstream network effects, and therapeutic strategies aimed at preserving or restoring these essential sleep rhythms.

None of the authors has any conflicts of interest to disclose. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.