Department of Basic and Clinical Neuroscience, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
Developmental Imaging and Biophysics Section, Developmental Neurosciences Program, UCL Great Ormond Street Institute of Child Health, London, UK.
Brain. 2018 Oct 1;141(10):2981-2994. doi: 10.1093/brain/awy223.
Generalized spike-wave discharges in idiopathic generalized epilepsy are conventionally assumed to have abrupt onset and offset. However, in rodent models, discharges emerge during a dynamic evolution of brain network states, extending several seconds before and after the discharge. In human idiopathic generalized epilepsy, simultaneous EEG and functional MRI shows cortical regions may be active before discharges, and network connectivity around discharges may not be normal. Here, in human idiopathic generalized epilepsy, we investigated whether generalized spike-wave discharges emerge during a dynamic evolution of brain network states. Using EEG-functional MRI, we studied 43 patients and 34 healthy control subjects. We obtained 95 discharges from 20 patients. We compared data from patients with discharges with data from patients without discharges and healthy controls. Changes in MRI (blood oxygenation level-dependent) signal amplitude in discharge epochs were observed only at and after EEG onset, involving a sequence of parietal and frontal cortical regions then thalamus (P < 0.01, across all regions and measurement time points). Examining MRI signal phase synchrony as a measure of functional connectivity between each pair of 90 brain regions, we found significant connections (P < 0.01, across all connections and measurement time points) involving frontal, parietal and occipital cortex during discharges, and for 20 s after EEG offset. This network prominent during discharges showed significantly low synchrony (below 99% confidence interval for synchrony in this network in non-discharge epochs in patients) from 16 s to 10 s before discharges, then ramped up steeply to a significantly high level of synchrony 2 s before discharge onset. Significant connections were seen in a sensorimotor network in the minute before discharge onset. This network also showed elevated synchrony in patients without discharges compared to healthy controls (P = 0.004). During 6 s prior to discharges, additional significant connections to this sensorimotor network were observed, involving prefrontal and precuneus regions. In healthy subjects, significant connections involved a posterior cortical network. In patients with discharges, this posterior network showed significantly low synchrony during the minute prior to discharge onset. In patients without discharges, this network showed the same level of synchrony as in healthy controls. Our findings suggest persistently high sensorimotor network synchrony, coupled with transiently (at least 1 min) low posterior network synchrony, may be a state predisposing to generalized spike-wave discharge onset. Our findings also show that EEG onset and associated MRI signal amplitude change is embedded in a considerably longer period of evolving brain network states before and after discharge events.
特发性全面性癫痫的泛化棘波放电通常被认为具有突然的起始和结束。然而，在啮齿动物模型中，放电是在脑网络状态的动态演变中出现的，放电前和放电后可延伸数秒。在人类特发性全面性癫痫中，同时进行脑电图和功能性磁共振成像显示皮质区域可能在放电前活跃，并且放电周围的网络连接可能不正常。在这里，我们研究了人类特发性全面性癫痫中泛化棘波放电是否在脑网络状态的动态演变中出现。使用 EEG-功能性 MRI，我们研究了 43 名患者和 34 名健康对照者。我们从 20 名患者中获得了 95 次放电。我们比较了有放电的患者的数据与无放电的患者和健康对照组的数据。仅在 EEG 起始时和之后观察到放电期 MRI（血氧水平依赖）信号幅度的变化，涉及顶叶和额叶皮质区域，然后是丘脑（所有区域和测量时间点的 P < 0.01）。作为脑网络之间功能连接的测量，检查 MRI 信号相位同步性，我们发现了显著的连接（所有连接和测量时间点的 P < 0.01），包括额叶、顶叶和枕叶皮质，在放电期间，以及在 EEG 结束后 20 秒。在放电期间出现的这个网络在放电期的网络同步性显著较低（在放电期非放电期患者的网络同步性置信区间 99%以下），然后在放电前 16 秒急剧上升到显著高的同步性水平。在放电前 1 分钟可以看到一个感觉运动网络中的显著连接。与健康对照组相比，该网络在无放电的患者中也显示出升高的同步性（P = 0.004）。在放电前 6 秒，观察到与这个感觉运动网络的额外显著连接，涉及前额叶和楔前叶区域。在健康受试者中，显著的连接涉及到一个后皮质网络。在有放电的患者中，这个后网络在放电前 1 分钟内显示出明显较低的同步性。在没有放电的患者中，这个网络的同步性与健康对照组相同。我们的研究结果表明，持续的高感觉运动网络同步性，加上短暂的（至少 1 分钟）后网络同步性降低，可能是导致泛化棘波放电发作的一种状态。我们的研究结果还表明，脑电图起始和相关的 MRI 信号幅度变化嵌入在放电前后更长的脑网络状态演变过程中。
