睡眠2期脑电信号产生的生理机制模型仿真研究

目前慢波睡眠生理机制研究已有的理论及动物实验结果显示,慢波睡眠中,皮层-丘脑系统神经元存在三种不同节律的振荡:慢振荡(<1 HZ)、δ振荡(1-4Hz)和纺锤振荡(7-14Hz)。这些神经元电活动在皮层水平广泛同步化,产生慢波睡眠脑电。提出了能分别产生这三种节律的三种神经元环路模型,并将之组合简化成一个七细胞环路模型。由这样的大量环路组成的网络模型在合适的突触连接参数范围内,能在皮层处产生人类慢波睡眠脑电2期的完整波形。这一结果说明了如何将动物实验观察到的睡眠生理机制的结果与人自然睡眠活动的脑电结果联系起来,并提示脑信息处理中由微观神经元群放电特征整合为脑的宏观功能状态的主要环节。     

神经递质在睡醒转换中作用的数学模型仿真研究

根据已有的生理解剖知识［１ ］ 提出了关于入睡机制的三细胞环路模型及其网络模型［２ ］ 。在文献［２］ 模型的基础上,根据神经递质在睡醒转换中的重要作用及其作用方式主要是通过影响丘脑中的两种离子流－ 钾的漏电流（ＩＫＬ） 和超极化激活的阳离子流（Ｉｈ） ,以及丘脑皮质系统中突触传递强度的变化而起作用的生理知识,修改了［２］ 中三细胞环路模型及其网络模型。模型仿真结果显示,在适当调节模型参数的条件下,确能使细胞环路产生入睡纺锤节律与觉醒快速放电之间的双向转换,其网络模型也能通过同步振荡在皮层处出现人脑电中规定入睡标志的特征纺锤波与规定觉醒期的低幅快波之间的双向转换。此结果又一次启示了脑信息处理中如何通过同步振荡机制将表示微观特性的神经元群放电特征整合为脑的宏观功能状态的过程。     

基于生理解剖知识的入睡机制神经元群网络模型研究

以生理解剖知识为基础,在已有的丘脑网状核细胞和丘脑皮质细胞间组成的入睡机制的两细胞环路模型［１］和由此两细胞环路组成的网络模型［２］的基础上,提出了增加皮层细胞在内的三种细胞组成的环路模型和网络模型,以使模型更符合近来认为睡眠机制是皮层和丘脑环路中出现特定的同步振荡的看法［３］。并能使模型的仿真结果可以和规定人体睡眠分期的脑电特征波相对应。这一网络模型的仿真结果,在一定条件下,确能在皮层细胞处出现符合睡眠分期中规定的标志入睡的纺锤波,这一初步结果,启示我们用模型仿真方法来进一步探讨睡眠机制和用模型仿真方法来进一步探讨人脑的微观神经元的电活动是如何通过同步振荡整合到宏观功能状态的某些信息处理过程的可能性。     

强直电刺激嗅内皮质—海马环路诱发CAI神经元的癫痫同步性膜电位振？…

目的和方法：４００－５００μｍ大鼠水平脑切片吸封闭的ＥＣ－海马环路。强直电刺激（６０Ｈｚ,２ｓ）海马Ｓｃｈａｅｆｆｅｒ侧支诱发癫痫放电,全细胞记录ＣＡ１胞体层单个神经元电活动,同步记录相应树突外场电位,探讨单个神经元膜电位振荡特性和细胞外癫痫电活动之间的关系。结果：（１）强直电刺激诱发ＣＡ１神经元膜电位后放性振呈宽频特征（３－１００ＨＺ）。以θ节律多见,跟随在刺激引起的膜电位去极化或超极化偏移之后     

睡眠纺锤波在植物状态病人预后判别中的价值研究

目的:探讨脑电图睡眠纺锤波在植物状态病人预后判别中的价值。方法:在长程脑电监测下观察植物状态病人的睡眠纺锤波,与其意识恢复进行相关性分析,并预测患者意识恢复的敏感性、特异性及准确性。结果:28例患者中,12例有纺锤波,其中9例意识恢复;16例无纺锤波患者中,14例未恢复意识。纺锤波的有无与患者意识恢复有相关性,P值<0.01。脑电图睡眠纺锤波对植物状态患者意识恢复判断的敏感性(83.25%)、特异性(81.82%)、准确性(82.14%)。结论:脑电图睡眠纺锤波可较准确预测植物状态患者的意识恢复能力,可作为临床评估植物状态患者意识恢复能力的辅助方法。     

睡眠稳态的电生理机制

大脑需要稳态系统来维持神经元的正常活动。睡眠不足会影响到有机体的生理功能,因此清醒时不断累积的睡眠压力会迫使哺乳动物进入睡眠状态,长时间清醒（睡眠剥夺）则会延长或加深随后的睡眠,这一现象被称为睡眠稳态（sleep homeostasis）。探明睡眠稳态的电生理机制有利于改善睡眠,治疗相关疾病,但目前仍存在许多问题。鉴于此,本文围绕睡眠稳态的电生理机制,首先关注睡眠稳态公认的电生理标志物——慢波活动,接下来介绍神经元放电率的相关研究,最后从脑区差异、睡眠阶段、学习记忆和物种差异几个方面进行展望。     

神经起步点产生的一种新型簇放电节律———阵发周期1节律

实验中发现了神经起步点产生的一种新型的簇放电节律－－阵发周期1节律。其特征如下：连续周期1放电与休止期（quiescence）轮流出现;非周期性,连续放电持续期、连续放电次数以及休止期有较大变异性;位于周期1节律和静息状态之间。具有较长周期的伪单色噪声激励的FHN（FizHugh-Nagumo）模型可以产生类似的阵发周期1节律。模型和实验中的阵发周期1节律的统计特征、变化规律和所处的参数区间相类似。这表明：阵发周期1节律是由与伪单色噪声类似的长时程振荡激励引起的。     

婴儿夜间睡眠脑电纺锤波的观察

婴儿夜间睡眠脑电纺锤波的观察张慧秀,朱国庆,张景行,孔秀（安徽医科大学睡眠障碍研究室,安徽医科大学附属医院合肥２３００３２）婴儿睡眠纺锤波是作为慢波睡眠（ＳＷＳ）的一个标志,也可作为中枢神经系统机能正常与否的一个指标。为了解婴儿睡眠纺锤波发育情况并明...     

大鼠慢波睡眠和睡眠过渡期脑电信号的小波变换分析

EEG信号经常包含许多快速的时变信息 ,将较长时间段的EEG信号近似看作平稳信号 ,进行FFT谱估计 ,存在其局限性。应用多分辨率小波变换方法 ,在频域和时域上可以同时定位分析大鼠慢波睡眠和睡眠过渡期脑电的动态变化特性。采用慢性埋植电极记录自由活动大鼠的皮层脑电 ,将信号用小波变换分解成δ、θ、α和 β四个分量 ,求各分量的功率和功率百分比的时间变化曲线 ,并与FFT功率谱分析结果进行比较。结果表明 :慢波睡眠期EEG中有 2 6 .2 %± 7.7%的时间段上δ分量功率小于总功率的 5 0 % ,且δ分量较大时 ,其他分量较小 ;δ分量较小时 ,其他分量较大 ,差别显著。此结果揭示了δ节律与θ和α节律之间的一种互补关系。而传统的FFT功率谱分析方法只能显示δ分量为主 (占总功率 70 .6 %± 6 .4 % )的功率谱 ,不能提供时变信息。对于睡眠过渡期的非稳态EEG信号 ,利用小波变换分解得到的θ和α分量可以鉴别出睡眠纺锤波 ,计算睡眠纺锤波的平均持续时间 ,并比较纺锤波和非纺锤波时期各个频谱分量的变化情况。由此可见 ,小波变换可用于计算新的EEG时频定量分析指标用于分析生理、病理和药理作用引起的睡眠EEG的变化过程 ,以弥补传统FFT功率谱分析的不足之处     

强直电刺激嗅内皮质-海马环路诱发CA1神经元的癫痫同步性膜电位振荡行为

目的和方法 :4 0 0～ 5 0 0 μm大鼠水平脑切片含有封闭的EC 海马环路。强直电刺激 (60Hz ,2s)海马Schaeffer侧支诱发癫痫放电 ,全细胞记录CA1胞体层单个神经元电活动 ,同步记录相应树突区细胞外场电位 ,探讨单个神经元膜电位振荡特性与细胞外癫痫电活动之间的关系。结果 :①强直电刺激诱发CA1神经元膜电位后放性振荡行为呈宽频特征 (3～ 10 0Hz)。以θ节律多见 ,跟随在刺激引起的膜电位去极化或超极化偏移 (paroxysmaldepolarizingorhyperpolaringshift,PDSorPHS)之后 ,振荡波的上升支和下降支分别由膜电位去极化 超极化或超极化 去极化成分构成 ;②逐渐增强的IPSP构成了膜电位振荡的起搏成分 ,继而反弹形成锋电位和阈下振荡 ,与细胞外癫痫样电活动同步 ,并促成癫痫放电由紧张性向阵挛性形式转变 ;③发现了电偶联电位 (spikelets)以及细胞之间的染料偶联现象。结论 :单个神经元作为振荡器可以启动群体神经元超同步化癫痫样电活动 ;缝隙连接可能参与了膜电位振荡的启动与场电位癫痫样电活动的同步作用。     

Generalized epilepsy with spike-wave paroxysms as an epileptic disorder of the function of sleep promotion

A new hypothesis is offered regarding the pathomechanism of generalized epilepsy with spike-wave paroxysms (GESw) based on the pertaining literature and personal investigations. The first section is devoted to a critical overview of the development of theories regarding GESw. The centrencephalic theory, the debate on subcortical versus cortical origin, the "corticoreticular" hypothesis of Gloor and, finally, the "dyshormic" concept of Niedermeyer are outlined. In the next section it is shown that there is a particular optimum zone between sleep and wakefulness and between REM and slow wave sleep which highly favours the occurrence of spike-wave paroxysms. According to our investigations into the dynamics within this critical zone, the spike-wave paroxysms always appear with characteristic fluctuations of the level of consciousness where the changes towards awakening are always followed by rebounds towards sleep. Hence, the dynamic properties of this unstable border zone become especially interesting in the genesis of spike-wave paroxysms. It has been shown that even without epilepsy, a dynamics can be observed in the micro-oscillations in the depth of sleep which could be interpreted according to the reciprocal induction regulation model. In our concept the process of falling asleep emerges from rebounds of the sleep promoting system in response to sensory inputs streaming in from the external environment. According to this model, arousal influences in sleep have a sleep promoting effect. We interpret in this way all synchronized EEG reactions elicited by sensory stimuli and we consider K-complex type synchronization reactions as a "building stone" of the process of falling asleep which contains the whole process in concentrated form. The manifold similarities between the K-complex and the spike-wave pattern are demonstrated. On this basis spike-wave paroxysms can be regarded as an epileptic "caricature" of the sleep induction momentum reflected in the K-complex phenomenon. Hence, the GESw is the epileptic disorder of the sleep promotion function. This hypothesis resolves and explains many contradictory features of our knowledge about this mechanism and gives a new biologically oriented framework for further research. In the light of the hypothesis it has been attempted to interpret some of the characteristic features of the GESw: the genetic determination, the age dependency, the link with the sleep-waking cycle as well as the functional-anatomical characteristics and the symptoms of the seizures.     

Alpha-bursts and K-complex: phasic activation pattern during spontaneous recovery of correct psychomotor performance at difference stages of drowsiness

It is known that phasic activation processes reveal themselves by different electrophysiological patterns depending on the sleep depth. Alpha bursts are an electrophysiological manifestation of arousal at the initial stage of sleep, whereas at the II stage K-complex becomes the main arousal pattern. We have shown earlier that during light drowsiness spontaneous recovery of correct psychomotor test performance (after an error) by a sitting subject is accompanied by EEG alpha bursts. The aim of this work was to study the EEG phasic activation pattern at deeper drowsiness during test performance by a subject in a lying position. Subjects had to press sensitive button in a lying position with closed eyes with self-paced oral counting of pressings. The experiment lasted for 40 min; EEG, EOG, and button pressing were recorded. It was shown that recovery of correct performance after errors at deeper drowsiness was accompanied by two types of EEG phasic activation patterns (PAP-1 and PAP-2). The alpha frequency component was always present in both PAP-1 and PAP-2. PAP-1 were observed at early stages of drowsiness and consisted of high-amplitude alpha bursts and EEG activity of higher frequency. PAP-2 were recorded at deeper stages and consisted of K-complexes with superposition of PAP-1. At first (medium level of drowsiness) the alpha bursts were superposed on the late slow K-complex components. With further deepening of drowsiness the early fast components of K-complex were also observed. The early appearance of K-complex during test performance at drowsiness seems to be associated with the urgent run of brain arousal systems, which at spontaneous falling asleep are in operation at the II sleep stage.     

A thalamo-cortical neural mass model for the simulation of brain rhythms during sleep

Cortico-thalamic interactions are known to play a pivotal role in many brain phenomena, including sleep, attention, memory consolidation and rhythm generation. Hence, simple mathematical models that can simulate the dialogue between the cortex and the thalamus, at a mesoscopic level, have a great cognitive value. In the present work we describe a neural mass model of a cortico-thalamic module, based on neurophysiological mechanisms. The model includes two thalamic populations (a thalamo-cortical relay cell population, TCR, and its related thalamic reticular nucleus, TRN), and a cortical column consisting of four connected populations (pyramidal neurons, excitatory interneurons, inhibitory interneurons with slow and fast kinetics). Moreover, thalamic neurons exhibit two firing modes: bursting and tonic. Finally, cortical synapses among pyramidal neurons incorporate a disfacilitation mechanism following prolonged activity. Simulations show that the model is able to mimic the different patterns of rhythmic activity in cortical and thalamic neurons (beta and alpha waves, spindles, delta waves, K-complexes, slow sleep waves) and their progressive changes from wakefulness to deep sleep, by just acting on modulatory inputs. Moreover, simulations performed by providing short sensory inputs to the TCR show that brain rhythms during sleep preserve the cortex from external perturbations, still allowing a high cortical activity necessary to drive synaptic plasticity and memory consolidation. In perspective, the present model may be used within larger cortico-thalamic networks, to gain a deeper understanding of mechanisms beneath synaptic changes during sleep, to investigate the specific role of brain rhythms, and to explore cortical synchronization achieved via thalamic influences.     

Thalamic T-type Ca2+ channels and NREM sleep

T-type Ca2+ channels play a number of different and pivotal roles in almost every type of neuronal oscillation expressed by thalamic neurones during non-rapid eye movement (NREM) sleep, including those underlying sleep theta waves, the K-complex and the slow (<1 Hz) sleep rhythm, sleep spindles and delta waves. In particular, the transient opening of T channels not only gives rise to the 'classical' low threshold Ca2+ potentials, and associated high frequency burst of action potentials, that are characteristically present during sleep spindles and delta waves, but also contributes to the high threshold bursts that underlie the thalamic generation of sleep theta rhythms. The persistent opening of a small fraction of T channels, i.e. I(Twindow), is responsible for the large amplitude and long lasting depolarization, or UP state, of the slow (<1 Hz) sleep oscillation in thalamic neurones. These cellular findings are in part matched by the wake-sleep phenotype of global and thalamic-selective CaV3.1 knockout mice that show a decreased amount of total NREM sleep time. T-type Ca2+ channels, therefore, constitute the single most crucial voltage-dependent conductance that permeates all activities of thalamic neurones during NREM sleep. Since I(Twindow) and high threshold bursts are not restricted to thalamic neurones, the cellular neurophysiology of T channels should now move away from the simplistic, though historically significant, view of these channels as being responsible only for low threshold Ca2+ potentials.     

Regional slow waves and spindles in human sleep

The most prominent EEG events in sleep are slow waves, reflecting a slow (<1 Hz) oscillation between up and down states in cortical neurons. It is unknown whether slow oscillations are synchronous across the majority or the minority of brain regions--are they a global or local phenomenon? To examine this, we recorded simultaneously scalp EEG, intracerebral EEG, and unit firing in multiple brain regions of neurosurgical patients. We find that most sleep slow waves and the underlying active and inactive neuronal states occur locally. Thus, especially in late sleep, some regions can be active while others are silent. We also find that slow waves can propagate, usually from medial prefrontal cortex to the medial temporal lobe and hippocampus. Sleep spindles, the other hallmark of NREM sleep EEG, are likewise predominantly local. Thus, intracerebral communication during sleep is constrained because slow and spindle oscillations often occur out-of-phase in different brain regions.     

Lessons about sleepiness and driving from the Selby rail disaster case: R v Gary Neil Hart

In April 2003, near the town of Selby in North Yorkshire, England, a motor vehicle went off the road to cause a train collision, killing 10 and injuring more than 70 people. The driver of the vehicle, Gary Neil Hart, had allegedly fallen asleep while driving, and was charged and subsequently convicted of causing death by dangerous driving. Evidence from an expert witness was led by the prosecution to establish that Hart had in fact fallen asleep, and that prior to falling asleep, he knew (or ought to have known) that he was at risk of falling asleep but nevertheless continued to drive. The issue of whether and to what extent individuals are aware that they are about to fall asleep has significant implications for criminal prosecutions. Generally, the definition of a criminal offense includes a mental element such as intent or knowledge. Therefore, it is imperative that issues such as whether in every individual there is forewarning of sleep and the degree to which individuals are able to self-assess their ability to continue driving under conditions of extreme sleepiness must be resolved. Sleepiness is now regarded as the largest identifiable and preventable cause of accidents in all modes of transportation. Litigation for such accidents is likely to increase, and therefore it is of great importance that further research be undertaken to examine the process of falling asleep, especially the subjective experiences immediately preceding sleep.     

Insomnia: zolpidem extended-release for the treatment of sleep induction and sleep maintenance symptoms

Insomnia impairs daytime functioning or causes clinically significant daytime distress. The consequences of insomnia, if left untreated, may contribute to the risks of developing additional serious conditions, such as psychiatric illness, cardiovascular disease, or metabolic issues. Furthermore, some comorbidities associated with insomnia may be bidirectional in their causality because psychiatric and other medical problems can increase the risk for insomnia. Regardless of the serious consequences of inadequately treated insomnia, clinicians often do not inquire into their patients' sleep habits, and patients, in turn, are not forthcoming with details of their sleep difficulties. The continuing education of physicians and patients with regard to insomnia and currently available therapies for the treatment of insomnia is, therefore, essential. Insomnia may present as either a difficulty falling asleep, difficulty maintaining sleep, or waking too early without being able to return to sleep. Furthermore, these symptoms often change over time in an unpredictable manner. Therefore, when considering a sleep medication, one with efficacy for the treatment of multiple insomnia symptoms is recommended. A modified-release formulation of zolpidem, zolpidem extended-release, has been approved for the treatment of insomnia characterized by both difficulty in falling asleep and maintaining sleep. Here, we review studies supporting the use of zolpidem extended-release in the treatment of sleep-onset and sleep maintenance difficulties.