EEG and Epilepsy Unit / Neurology, Department of Clinical Neuroscience, University Hospitals and Faculty of Medicine of University of Geneva, Geneva, Switzerland.
Department of Basic Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Epilepsia. 2021 Oct;62(10):2357-2371. doi: 10.1111/epi.17020. Epub 2021 Aug 2.
In patients with epilepsy, interictal epileptic discharges are a diagnostic hallmark of epilepsy and represent abnormal, so-called "irritative" activity that disrupts normal cognitive functions. Despite their clinical relevance, their mechanisms of generation remain poorly understood. It is assumed that brain activity switches abruptly, unpredictably, and supposedly randomly to these epileptic transients. We aim to study the period preceding these epileptic discharges, to extract potential proepileptogenic mechanisms supporting their expression.
We used multisite intracortical recordings from patients who underwent intracranial monitoring for refractory epilepsy, the majority of whom had a mesial temporal lobe seizure onset zone. Our objective was to evaluate the existence of proepileptogenic windows before interictal epileptic discharges. We tested whether the amplitude and phase synchronization of slow oscillations (.5-4 Hz and 4-7 Hz) increase before epileptic discharges and whether the latter are phase-locked to slow oscillations. Then, we tested whether the phase-locking of neuronal activity (assessed by high-gamma activity, 60-160 Hz) to slow oscillations increases before epileptic discharges to provide a potential mechanism linking slow oscillations to interictal activities.
Changes in widespread slow oscillations anticipate upcoming epileptic discharges. The network extends beyond the irritative zone, but the increase in amplitude and phase synchronization is rather specific to the irritative zone. In contrast, epileptic discharges are phase-locked to widespread slow oscillations and the degree of phase-locking tends to be higher outside the irritative zone. Then, within the irritative zone only, we observe an increased coupling between slow oscillations and neuronal discharges before epileptic discharges.
Our results show that epileptic discharges occur during vulnerable time windows set up by a specific phase of slow oscillations. The specificity of these permissive windows is further reinforced by the increased coupling of neuronal activity to slow oscillations. These findings contribute to our understanding of epilepsy as a distributed oscillopathy and open avenues for future neuromodulation strategies aiming at disrupting proepileptic mechanisms.
在癫痫患者中，发作间期癫痫放电是癫痫的诊断标志，代表异常的、所谓的“刺激性”活动，扰乱了正常的认知功能。尽管它们具有临床相关性，但它们的产生机制仍知之甚少。据推测，大脑活动会突然、不可预测地、且据称是随机地切换到这些癫痫发作。我们旨在研究这些癫痫发作之前的时期，以提取支持其表达的潜在致癫痫机制。
我们使用来自接受颅内监测的难治性癫痫患者的多部位皮质内记录，其中大多数患者的内侧颞叶起始区有癫痫发作。我们的目的是评估发作间期癫痫放电前是否存在致癫痫窗口。我们测试了在癫痫放电之前，慢波（.5-4 Hz 和 4-7 Hz）的振幅和相位同步是否增加，以及后者是否与慢波锁相。然后，我们测试了神经元活动（通过高伽马活动，60-160 Hz 评估）到慢波的锁相是否在癫痫放电之前增加，以提供一种将慢波与发作间期活动联系起来的潜在机制。
广泛的慢波变化预示着即将发生的癫痫放电。网络扩展到刺激性区域之外，但振幅和相位同步的增加相当特定于刺激性区域。相比之下，癫痫放电与广泛的慢波锁相，锁相程度在刺激性区域之外往往更高。然后，仅在刺激性区域内，我们观察到在癫痫放电之前，慢波和神经元放电之间的耦合增加。
我们的结果表明，癫痫发作发生在由慢波特定相位设置的脆弱时间窗口内。这些允许窗口的特异性进一步由神经元活动与慢波的耦合增加所加强。这些发现有助于我们理解癫痫作为一种分布式振荡病，并为未来旨在破坏致癫痫机制的神经调节策略开辟了途径。
