伤害性感受失匹配负波及其提取方法的研究

发布时间：2018-04-19 13:48

本文选题：失匹配负波(MMN) + 事件相关电位(ERP)　；参考：《西南大学》2014年硕士论文

【摘要】：白1978年Naatanen等科学家发现了听觉的失匹配负波(Mismatch Negativity:MMN)这现象以来,失匹配负波就成为了认知神经科学研究的一个热点问题。从近年来听觉失匹配负波在临床研究中的应用可以看出,听觉失匹配负波作为对患者意识水平的准确预测是令人意外的。这也表明失匹配负波这一指标在临床研究及应用方面已经初露头角。那么,利用有效的伤害性感受失匹配负波信号作为一个客观的探测指标来服务于疼痛临床研究可以克服患者认知、语言表达、情绪情感等因素对疼痛测量准确性的影响,对帮助医生更准确、高效的诊断和测量疼痛,并有效选择镇痛手段都有很大帮助,对于疼痛的临床治疗也有非常深远的意义。除了听觉模态之外,不同感觉模态的失匹配负波现象也逐步得到研究验证(例如：视觉,触觉),然而在痛觉模态,失匹配负波还是鲜有涉及的领域。这主要是由于失匹配负波本身特有的电生理学特性,即已有研究表明其具有很低的信噪比,即使在研究最广泛的听觉模态中,一些被试MMN脑电响应的平均波幅尚且不高于5μV。相比于听觉MMN脑电响应,非伤害性触觉系统和伤害性感受系统的MMN脑电响应的信噪比更低,在单个被试水平上甚至没有一个清晰的失匹配负波波峰,因此探测伤害性系统的MMN脑电响应非常困难。本研究拟通过两个实验(即两个层面：实验设计的改进和数据分析的优化)来提取稳定的伤害性感受失匹配负波。实验一试探性地证明伤害性感受MMN现象的存在；实验二通过改进实验范式和优化数据分析方法进一步探讨伤害性感受MMN的形成机制。实验一为被试内设计,共有两种注意条件：一种要求被试将注意力集中在感觉刺激上(积极注意条件active condition),另一种要求被试将注意力从感觉刺激上转移开(消极注意条件passive condition)。非伤害性触觉刺激与伤害性感受刺激分别在不同的block呈现。通过巡回范式的设计将一连串非伤害性触觉刺激或伤害性感受刺激分别传递到被试左手或右手手背的侧部(lateral, L),中部(median, L),和腕部(wrist, W)三个位置上,由此来诱发非伤害性触觉失匹配负波以及伤害性感受失匹配负波。即每一串刺激中第一个刺激是偏差刺激,始于三个手部位置中的一个,该刺激串结束后,进入另一个手部位置刺激串的输出。每一串刺激都由4-8个相同的重复刺激(刺激数目在所有刺激串中随机分布)组成,刺激呈现的时间间隔是1000ms。实验一中,我们主要获得了三项发现。首先,在非伤害性触觉感受诱发电位和伤害性感受诱发电位中,失匹配主效应(偏差刺激,标准刺激)显著存在于三个空间区域内,即双侧颞叶区域以及中央区域(图2,4)。其次,我们提取了失匹配主效应在显著的空间兴趣区内的波形以及波幅。我们发现失匹配主效应在由非伤害性刺激以及伤害性刺激所诱发的早期和晚期的脑电响应中都显著。同时也表明了不论注意是否对脑电响应具有影响作用,非伤害性触觉诱发电位和伤害性诱发电位对规律的破坏都具有较高的敏感性(图3,5)。最后,在失匹配主效应所在的空间兴趣区内,根据普遍接受的MMN出现的潜伏期区间(100-250ms),我们提取了仅受失匹配因素影响而不受注意因素影响的波幅(图6)。综上所述,这些发现表明,(1)如同非伤害性触觉感受失匹配负波一样,伤害性刺激也可以引发失匹配大脑响应,但是也不能忽视注意的影响作用。(2)非伤害性触觉失匹配响应与伤害性感受失匹配响应的头皮地形图很相似,但是二者的头皮地形图在施加刺激的对侧大脑颞叶区域和同侧大脑颞叶区域的响应起始时间上却有质的区别。实验二依然是被试内设计,共有两种注意条件：一种是要求被试将注意集力中在感觉刺激上(积极注意条件active condition),另一种要求被试将注意力从感觉刺激上转移开(消极注意条件passive condition)。同样采用巡回范式的设计。与实验一设计的不同点在于,实验二中有三种感觉刺激,分别为听觉刺激,非伤害性触觉刺激,伤害性感觉刺激。三种感觉模态(听觉,非伤害性触觉,伤害性感受)的刺激呈现在同一block中,且遵守连续的两个刺激串不能来自同一感觉模态的原则,以伪随机的方式排列三种感觉刺激串。通过三种刺激的感觉模态的改变作为巡回范式的变量,即每一串刺激中第一个刺激是偏差刺激,始于一种感觉模态(听觉,非伤害性触觉,或伤害性感受),随着刺激的重复成为标准刺激。该刺激串结束后,进入另一感觉模态的刺激串的刺激输出。每个刺激串中有11-15个具有相同物理特性的刺激(来自于同一感觉模态的相同感觉刺激),刺激间的时间间隔为1000ms,每个刺激串中刺激数目也以伪随机的方式排布。实验二提供了在不同感觉模态提取失匹配负波有效且可靠的方法,且表明感觉记忆痕的形成以及偏差刺激探测在某种程度上是感觉模态特异的。总结起来我们主要有四项发现：(1)不同感觉刺激引发的失匹配负波响应可以用基于地形图的分段分析方法来提取。即使在脑电响应中没有清晰的波峰时,使用这种分析方法也能够将与失匹配负波功能相关的脑电活动提取出来。(2)三种感觉模态中的刺激重复两次后(至少两次)标准刺激便可以形成(即在第三个刺激位置之后的刺激响应之间差别微小),不论是否注意感觉刺激,也不论刺激串前是何种感觉模态的刺激串。(3)一旦稳定的标准刺激形成后,其后刺激串中的偏差刺激(刺激串中第一个刺激)会受到前面感觉模态的影响。(4)在同一感觉模态中,积极注意和消极注意条件下的失匹配负波的波幅有较强的相关关系,而在不同的感觉模态间这种相关关系并不存在。本研究通过两个实验研究证实了伤害性感受失匹配负波的存在,详细描述了伤害性感受失匹配负波的潜伏期区间、波形、头皮地形图,并开发了提取失匹配负波可靠的、高效的方法。又通过对比听觉以及非伤害性触觉模态的MMN脑电响应,进一步探讨了失匹配负波内在神经生理学机制。本研究成功的证实了伤害性感受失匹配负波的存在,填补了在痛觉领域失匹配负波研究的空白,对于失匹配负波在多种感觉通道的研究有补充作用。另外,伤害性感受失匹配负波作为客观的神经生理学指标,为慢性疼痛患者在非注意情况下的疼痛处理机制研究提供了良好的观察治疗手段,在疼痛的临床治疗方面具有非常重要的意义。
[Abstract]:Since Naatanen and other scientists discovered the auditory mismatch negative wave (Mismatch Negativity:MMN) in 1978, mismatched negative waves have become a hot issue in cognitive neuroscience research. The application of hearing mismatched negative waves in clinical studies in recent years shows that hearing mismatched negative waves are regarded as the level of consciousness of patients. The accurate prediction is surprising. It also shows that the mismatched negative wave is the first appearance in clinical research and application. Then, using the effective nociceptive mismatched negative wave signal as an objective detection index to serve the clinical research of pain can take the patient's cognition, language expression, emotional emotion and so on. The effect of hormone on the accuracy of pain measurement is of great help to help doctors more accurately, effectively diagnose and measure pain, and to effectively choose analgesic means. It is also of profound significance for the clinical treatment of pain.
In addition to the auditory modality, the mismatched negative wave phenomena of different sensory modes have been gradually verified (for example: vision, tactile), but in the pain mode, the mismatched negative waves are still rarely involved. This is mainly due to the characteristic electrophysiological characteristics of the mismatched negative wave itself, that is, it has been shown to have a very low signal to noise ratio. Even in the most widely studied auditory modalities, the average amplitude of some MMN EEG responses is not higher than 5 mu V. compared to the auditory MMN EEG, and the SNR of the MMN EEG response of the non nociceptive system and the nociceptive system is lower, and there is not even a clear mismatched negative wave peak at a single test level. The MMN EEG response of the detection nociceptive system is very difficult.
In this study, a stable nociceptive mismatched negative wave was extracted from two experiments (two levels: experimental design improvement and data analysis optimization). Experiment 1 tentatively proved the existence of MMN phenomenon of nociceptive sex; experiment two further explored the nociceptive sensual MM by improving the experimental paradigm and optimizing the data analysis method. The formation mechanism of N.
In the experiment, there were two kinds of attention conditions: one required the subjects to focus on the sensory stimulation (active attention to the condition active condition), and the other required the subjects to divert the attention from the sensory stimulation (negative attention condition passive condition). A series of non destructive tactile stimuli or nociceptive stimuli were transmitted to the lateral part of the left hand or right hand back (lateral, L), the middle (median, L), and the wrist (wrist, W) three positions, which induced non nociceptive tactile mismatch negative waves and nociceptive sensual reception by the design of the circuit paradigm. A mismatched negative wave. That is, the first stimulus in each string is a deviant stimulus, which begins with one of the three hand positions. After the end of the stimulus string, the output of the string is stimulated at the other hand position. Each string of stimuli is composed of 4-8 identical repetitive stimuli (the number of stimuli is randomly distributed among all the spiny strings), and the stimulus is present. Isolation is 1000ms.
In the first experiment, we mainly obtained three discoveries. First, in the non nociceptive and nociceptive evoked potentials and nociceptive evoked potentials, the mismatch main effect (deviation stimulation, standard stimulus) exists in the three spatial regions, namely the bilateral temporal lobe region and the central region (Figure 2,4). Secondly, we extract the mismatched main effect. We find that the mismatch main effect is significant in the early and late EEG responses induced by non nociceptive stimuli and nociceptive stimuli in significant spatial interest zones. The generation position has high sensitivity to the damage of the law (Figure 3,5). Finally, in the space interest area where the mismatched main effect is located, we extract the amplitude of the amplitude (100-250ms), which is only affected by the mismatch factor and not affected by the attention factor (Figure 6). These findings indicate that (1) Like the non nociceptive sense of tactile mismatch negative wave, the nociceptive stimulus can also cause the mismatched brain response, but it can not ignore the effect of attention. (2) the non nociceptive tactile mismatch response is similar to the scalp map of the nociceptive mismatched response, but the scalp map of the two is applied to the opposite side of the stimulus. There is a qualitative difference in the response time between the temporal lobe area and the ipsilateral temporal lobe region.
In experiment two, there are still two kinds of attention in the design. One is to require the subjects to pay attention to the sensory stimulation (active attention to active condition) in the set force, and the other is to transfer the attention from the sensory stimulation (negative attention condition passive condition). The difference in the design is that there are three sensory stimuli in Experiment 2: auditory stimuli, non nociceptive tactile stimuli and nociceptive stimuli. Three sensory modalities (hearing, non nociceptive touch, nociceptive sensibility) are presented in the same block, and the continuous two stimulus strings are not derived from the same sensory modality principle. Three sensory stimulation strings are arranged in a pseudo random manner. By changing the sensory modality of the three stimuli as a variable of the circuit paradigm, the first stimulus in each string of stimuli is a bias stimulus, which begins with a sensory modality (hearing, non nociceptive touch, or nociceptive), with the repetition of the stimulus as a standard stimulus. The stimulus string ends. In each stimulus string, there are 11-15 stimuli with the same physical characteristics (from the same sensory stimulation from the same sensory modality) in each stimulus string. The time interval between the stimuli is 1000ms, and the number of stimuli in each stimulation string is also arranged in a pseudo random manner.
Experiment two provides an effective and reliable method to extract mismatched negative waves from different sensory modality, and indicates that the formation of sensory memory marks and the bias stimulus detection are sensory modality specific to some extent. In conclusion, we mainly have four discoveries: (1) the mismatched negative wave response caused by different sensory stimuli can be based on the terrain The sectional analysis method of the graph is used to extract. Even if there is no clear wave peak in the EEG response, this method can also extract the EEG activity associated with the mismatched negative wave function. (2) the stimulation of the stimuli in the three sensory modes (at least two times) can be formed (at the third stimulation positions. The difference between the stimulus response and the stimulus response is small, regardless of whether the stimuli are noticed or whether the stimuli are stimulated by the stimuli. (3) once the stable standard stimulus is formed, the bias stimulus in the subsequent stimulus string (the first stimulus in the stimulus string) is affected by the anterior sensory modality. (4) in the same sensory mode, it is positive. There is a strong correlation between the amplitude of mismatch negativity and negative attention, but there is no correlation between different sensory modality.
This study confirmed the existence of nociceptive mismatched negative waves in two experimental studies, described the interval of latent period, waveform, scalp topographic map of nociceptive and mismatched negative waves in detail, and developed a reliable and efficient method for extracting mismatched negative waves. By comparing the MMN EEG response of auditory and non injurious tactile modalities, To further explore the mismatch negative wave in the neurophysiological mechanism.
This study successfully confirmed the existence of nociceptive mismatched negative waves, filled the gap in the study of mismatched negative waves in the field of pain, and supplemented the study of mismatched negative waves in many sensory channels. In addition, the nociceptive mismatched negative wave was used as an objective neurophysiological index for the patients with chronic pain in non attention. The research on pain management mechanism provides a good way to observe and treat pain, and is of great importance in the clinical treatment of pain.

【学位授予单位】：西南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：B845

【共引文献】