Institute for Psychology, Hungarian Academy of Sciences, Budapest, Hungary.
Brain. 2010 Sep;133(9):2814-29. doi: 10.1093/brain/awq169. Epub 2010 Jul 23.
Brain electrical activity is largely composed of oscillations at characteristic frequencies. These rhythms are hierarchically organized and are thought to perform important pathological and physiological functions. The slow wave is a fundamental cortical rhythm that emerges in deep non-rapid eye movement sleep. In animals, the slow wave modulates delta, theta, spindle, alpha, beta, gamma and ripple oscillations, thus orchestrating brain electrical rhythms in sleep. While slow wave activity can enhance epileptic manifestations, it is also thought to underlie essential restorative processes and facilitate the consolidation of declarative memories. Animal studies show that slow wave activity is composed of rhythmically recurring phases of widespread, increased cortical cellular and synaptic activity, referred to as active- or up-state, followed by cellular and synaptic inactivation, referred to as silent- or down-state. However, its neural mechanisms in humans are poorly understood, since the traditional intracellular techniques used in animals are inappropriate for investigating the cellular and synaptic/transmembrane events in humans. To elucidate the intracortical neuronal mechanisms of slow wave activity in humans, novel, laminar multichannel microelectrodes were chronically implanted into the cortex of patients with drug-resistant focal epilepsy undergoing cortical mapping for seizure focus localization. Intracortical laminar local field potential gradient, multiple-unit and single-unit activities were recorded during slow wave sleep, related to simultaneous electrocorticography, and analysed with current source density and spectral methods. We found that slow wave activity in humans reflects a rhythmic oscillation between widespread cortical activation and silence. Cortical activation was demonstrated as increased wideband (0.3-200 Hz) spectral power including virtually all bands of cortical oscillations, increased multiple- and single-unit activity and powerful inward transmembrane currents, mainly localized to the supragranular layers. Neuronal firing in the up-state was sparse and the average discharge rate of single cells was less than expected from animal studies. Action potentials at up-state onset were synchronized within +/-10 ms across all cortical layers, suggesting that any layer could initiate firing at up-state onset. These findings provide strong direct experimental evidence that slow wave activity in humans is characterized by hyperpolarizing currents associated with suppressed cell firing, alternating with high levels of oscillatory synaptic/transmembrane activity associated with increased cell firing. Our results emphasize the major involvement of supragranular layers in the genesis of slow wave activity.
脑电活动主要由特征频率的振荡组成。这些节律是分层组织的，被认为具有重要的病理和生理功能。慢波是一种基本的皮质节律，出现在深度非快速眼动睡眠中。在动物中，慢波调制 delta、theta、纺锤波、alpha、beta、gamma 和涟漪振荡，从而协调睡眠中的脑电节律。虽然慢波活动可以增强癫痫发作的表现，但它也被认为是基本恢复过程的基础，并有助于陈述性记忆的巩固。动物研究表明，慢波活动由广泛的、增加的皮质细胞和突触活动的周期性重复相组成，称为活动或上相，随后是细胞和突触失活，称为沉默或下相。然而，其在人类中的神经机制尚不清楚，因为在动物中使用的传统细胞内技术不适合研究人类的细胞和突触/跨膜事件。为了阐明人类慢波活动的皮质内神经元机制，新型的、分层的多通道微电极被慢性植入到接受皮质映射以定位癫痫灶的耐药性局灶性癫痫患者的皮质中。在慢波睡眠期间记录皮质内分层局部场电位梯度、多单位和单单位活动，与同时的皮层电图相关，并使用电流源密度和光谱方法进行分析。我们发现，人类的慢波活动反映了广泛的皮质激活和沉默之间的节律性振荡。皮质激活表现为宽带（0.3-200 Hz）光谱功率增加，包括皮质振荡的几乎所有频段，多单位和单单位活动增加，以及强大的内向跨膜电流，主要定位于颗粒上层。在上相中神经元放电稀疏，单个细胞的平均放电率低于动物研究的预期。在所有皮质层中，在 +/-10 ms 内同步出现动作电位，这表明任何一层都可以在启动上相时开始放电。这些发现提供了强有力的直接实验证据，表明人类的慢波活动的特征是与细胞放电抑制相关的去极化电流，与细胞放电增加相关的高水平振荡突触/跨膜活动交替出现。我们的结果强调了颗粒上层在慢波活动产生中的主要作用。
