Department of Neurology & Neurosurgery, Biomedical Engineering and Computer Science, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Department of Neurology & Neurosurgery, Biomedical Engineering and Computer Science, Montreal Neurological Institute, McGill University, Montreal, QC, Canada; Department of Neurology & Neurosurgery and of Physiology, McGill University, Montreal, QC, Canada.
Neurobiol Dis. 2018 Jun;114:111-119. doi: 10.1016/j.nbd.2018.02.008. Epub 2018 Feb 24.
Polyrhythmic coupling of oscillatory components in electrophysiological signals results from the interactions between neuronal sub-populations within and between cell assemblies. Since the mechanisms underlying epileptic disorders should affect such interactions, abnormal level of cross-frequency coupling is expected to provide a signal marker of epileptogenesis. We measured phase-amplitude coupling (PAC), a form of cross-frequency coupling between neural oscillations, in a rodent model of mesial temporal lobe epilepsy. Sprague-Dawley rats (n = 4, 250-300 g) were injected with pilocarpine (380 mg/kg, i.p) to induce a status epilepticus (SE) that was stopped after 1 h with diazepam (5 mg/kg, s.c.) and ketamine (50 mg/kg, s.c.). Control animals (n = 6) did not receive any injection or treatment. Three days after SE, all animals were implanted with bipolar electrodes in the hippocampal CA3 subfield, entorhinal cortex, dentate gyrus and subiculum. Continuous video/EEG recordings were performed 24/7 at a sampling rate of 2 kHz, over 15 consecutive days. Pilocarpine-treated animals showed interictal spikes (5.25 (±2.5) per minute) and seizures (n = 32) that appeared 7 (±0.8) days after SE. We found that CA3 was the seizure onset zone in most epileptic animals, with stronger ongoing PAC coupling between seizures than in controls (Kruskal-Wallis test: chi (1,36) = 46.3, Bonferroni corrected, p < 0.001). Strong PAC in CA3 occurred between the phase of slow-wave oscillations (<1 Hz) and the amplitude of faster rhythms (50-180 Hz), with the strongest bouts of high-frequency activity occurring preferentially on the ascending phase of the slow wave. We also identified that cross-frequency coupling in CA3 (rho = 0.44, p < 0.001) and subiculum (rho = 0.41, p < 0.001) was positively correlated with the daily number of seizures. Overall, our study demonstrates that cross-frequency coupling may represent a signal marker in epilepsy and suggests that this methodology could be transferred to clinical scalp MEG and EEG recordings.
电生理信号中振荡成分的多韵律耦合是由细胞集合内和细胞集合之间的神经元亚群相互作用产生的。由于癫痫疾病的发病机制应该会影响这种相互作用，因此异常的跨频耦合水平有望提供癫痫发生的信号标志物。我们在颞叶内侧癫痫的啮齿动物模型中测量了相位-振幅耦合（PAC），这是一种神经振荡之间的跨频耦合形式。Sprague-Dawley 大鼠（n=4，250-300g）腹腔注射毛果芸香碱（380mg/kg）诱导癫痫持续状态（SE），1 小时后用地西泮（5mg/kg，sc）和氯胺酮（50mg/kg，sc）停止 SE。对照组动物（n=6）未接受任何注射或治疗。SE 后 3 天，所有动物均在海马 CA3 亚区、内嗅皮层、齿状回和下托植入双极电极。以 2kHz 的采样率连续进行 24/7 的视频/EEG 记录，持续 15 天。毛果芸香碱处理的动物表现出间发性棘波（每分钟 5.25（±2.5）次）和癫痫发作（n=32），SE 后 7（±0.8）天出现。我们发现 CA3 是大多数癫痫动物的发作起始区，发作之间的持续 PAC 耦合比对照组更强（Kruskal-Wallis 检验：chi(1,36)=46.3，Bonferroni 校正，p<0.001）。CA3 中的强 PAC 发生在慢波振荡（<1Hz）的相位和更快节律（50-180Hz）的幅度之间，高频活动的最强爆发优先发生在慢波的上升相位上。我们还发现 CA3（rho=0.44，p<0.001）和下托（rho=0.41，p<0.001）的跨频耦合与每日癫痫发作次数呈正相关。总的来说，我们的研究表明，跨频耦合可能是癫痫的一个信号标志物，并表明这种方法可以转移到临床头皮 MEG 和 EEG 记录中。
