Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex
Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex
复制标题
DOI：
10.1093/brain/awq112
复制
发表时间：
2010-06-01
期刊：
影响因子：
14.5
通讯作者：
Cash, Sydney S.
中科院分区：
文献类型：
--
作者：
Keller, Corey J.;Truccolo, Wilson;Cash, Sydney S.
癫痫皮层的特征是阵发性放电。这些发作间期放电的分析通常表现为脑电图上的棘波复合体，并且在诊断和治疗癫痫中起着关键作用。尽管它们具有根本的重要性，但人们对人类局灶性癫痫中产生这些事件的神经生理机制知之甚少。使用三种不同的微电极系统，我们记录了局部场电位和单位动作电位发作间期放电的药物难治性局灶性癫痫患者进行诊断性检查癫痫发作病灶的定位。我们研究了20例患者的336个单单位。对10个不同的皮质区和海马体进行了取样，包括癫痫发作病灶内外的区域。在其中三名患者中，高密度微电极阵列同时记录了来自小块（4 mm x 4 mm）皮质的43至166个单个单位。我们通过确定事件期间的放电率是否相同，高于或低于根据发作间期无放电期估计的中位基线放电率来检查单个神经元的放电率在发作间期放电期间如何变化（Kruskal-Wallis单向分析，P < 0.05）。只有48%的记录单位表现出这样的调制放电500毫秒内的放电率。在放电过程中调制的单位表现出显着更高的基线发射和爆裂率比未调制的单位。正如预期的那样，许多单位（27%的调制群体）在放电的快段（+/- 35 ms，从放电的峰值）期间显示出放电率增加，而50%的单位在慢波期间显示出降低。值得注意的是，与基于纯粹阵发性去极化移位模型的预测直接相反，在癫痫发作病灶内或附近记录的7.7%的调制单位在放电开始前（0-300 ms）显示活动减少，而12.2%的单位在此期间活动增加。在癫痫发作病灶以外的区域没有观察到这种放电前变化。在许多记录中，在同一放电前期间，宽带场电位活动也有所减少。发作间期调制放电的不同模式被分为15个以上的不同类别。这种异质性在单个单位的活动，以及内部和外部的癫痫发作区的小皮质区域内，这表明癫痫患者的发作间期癫痫样活动不是一个简单的超同步兴奋活动的发作，而是复杂的神经元网络内的多种不同的神经元类型的相互作用。
Epileptic cortex is characterized by paroxysmal electrical discharges. Analysis of these interictal discharges typically manifests as spike-wave complexes on electroencephalography, and plays a critical role in diagnosing and treating epilepsy. Despite their fundamental importance, little is known about the neurophysiological mechanisms generating these events in human focal epilepsy. Using three different systems of microelectrodes, we recorded local field potentials and single-unit action potentials during interictal discharges in patients with medically intractable focal epilepsy undergoing diagnostic workup for localization of seizure foci. We studied 336 single units in 20 patients. Ten different cortical areas and the hippocampus, including regions both inside and outside the seizure focus, were sampled. In three of these patients, high density microelectrode arrays simultaneously recorded between 43 and 166 single units from a small (4 mm x 4 mm) patch of cortex. We examined how the firing rates of individual neurons changed during interictal discharges by determining whether the firing rate during the event was the same, above or below a median baseline firing rate estimated from interictal discharge-free periods (Kruskal-Wallis one-way analysis, P < 0.05). Only 48% of the recorded units showed such a modulation in firing rate within 500 ms of the discharge. Units modulated during the discharge exhibited significantly higher baseline firing and bursting rates than unmodulated units. As expected, many units (27% of the modulated population) showed an increase in firing rate during the fast segment of the discharge (+/- 35 ms from the peak of the discharge), while 50% showed a decrease during the slow wave. Notably, in direct contrast to predictions based on models of a pure paroxysmal depolarizing shift, 7.7% of modulated units recorded in or near the seizure focus showed a decrease in activity well ahead (0-300 ms) of the discharge onset, while 12.2% of units increased in activity in this period. No such pre-discharge changes were seen in regions well outside the seizure focus. In many recordings there was also a decrease in broadband field potential activity during this same pre-discharge period. The different patterns of interictal discharge-modulated firing were classified into more than 15 different categories. This heterogeneity in single unit activity was present within small cortical regions as well as inside and outside the seizure onset zone, suggesting that interictal epileptiform activity in patients with epilepsy is not a simple paroxysm of hypersynchronous excitatory activity, but rather represents an interplay of multiple distinct neuronal types within complex neuronal networks.