本文選題：失匹配負波(MMN) + 事件相關電位(ERP)�。� 參考：《西南大學》2014年碩士論文

【摘要】：白1978年Naatanen等科學家發(fā)現了聽覺的失匹配負波(Mismatch Negativity:MMN)這現象以來,失匹配負波就成為了認知神經科學研究的一個熱點問題。從近年來聽覺失匹配負波在臨床研究中的應用可以看出,聽覺失匹配負波作為對患者意識水平的準確預測是令人意外的。這也表明失匹配負波這一指標在臨床研究及應用方面已經初露頭角。那么,利用有效的傷害性感受失匹配負波信號作為一個客觀的探測指標來服務于疼痛臨床研究可以克服患者認知、語言表達、情緒情感等因素對疼痛測量準確性的影響,對幫助醫(yī)生更準確、高效的診斷和測量疼痛,并有效選擇鎮(zhèn)痛手段都有很大幫助,對于疼痛的臨床治療也有非常深遠的意義。 除了聽覺模態(tài)之外,不同感覺模態(tài)的失匹配負波現象也逐步得到研究驗證(例如：視覺,觸覺),然而在痛覺模態(tài),失匹配負波還是鮮有涉及的領域。這主要是由于失匹配負波本身特有的電生理學特性,即已有研究表明其具有很低的信噪比,即使在研究最廣泛的聽覺模態(tài)中,一些被試MMN腦電響應的平均波幅尚且不高于5μV。相比于聽覺MMN腦電響應,非傷害性觸覺系統(tǒng)和傷害性感受系統(tǒng)的MMN腦電響應的信噪比更低,在單個被試水平上甚至沒有一個清晰的失匹配負波波峰,因此探測傷害性系統(tǒng)的MMN腦電響應非常困難。 本研究擬通過兩個實驗(即兩個層面：實驗設計的改進和數據分析的優(yōu)化)來提取穩(wěn)定的傷害性感受失匹配負波。實驗一試探性地證明傷害性感受MMN現象的存在；實驗二通過改進實驗范式和優(yōu)化數據分析方法進一步探討傷害性感受MMN的形成機制。 實驗一為被試內設計,共有兩種注意條件：一種要求被試將注意力集中在感覺刺激上(積極注意條件active condition),另一種要求被試將注意力從感覺刺激上轉移開(消極注意條件passive condition)。非傷害性觸覺刺激與傷害性感受刺激分別在不同的block呈現。通過巡回范式的設計將一連串非傷害性觸覺刺激或傷害性感受刺激分別傳遞到被試左手或右手手背的側部(lateral, L),中部(median, L),和腕部(wrist, W)三個位置上,由此來誘發(fā)非傷害性觸覺失匹配負波以及傷害性感受失匹配負波。即每一串刺激中第一個刺激是偏差刺激,始于三個手部位置中的一個,該刺激串結束后,進入另一個手部位置刺激串的輸出。每一串刺激都由4-8個相同的重復刺激(刺激數目在所有刺激串中隨機分布)組成,刺激呈現的時間間隔是1000ms。 實驗一中,我們主要獲得了三項發(fā)現。首先,在非傷害性觸覺感受誘發(fā)電位和傷害性感受誘發(fā)電位中,失匹配主效應(偏差刺激,標準刺激)顯著存在于三個空間區(qū)域內,即雙側顳葉區(qū)域以及中央區(qū)域(圖2,4)。其次,我們提取了失匹配主效應在顯著的空間興趣區(qū)內的波形以及波幅。我們發(fā)現失匹配主效應在由非傷害性刺激以及傷害性刺激所誘發(fā)的早期和晚期的腦電響應中都顯著。同時也表明了不論注意是否對腦電響應具有影響作用,非傷害性觸覺誘發(fā)電位和傷害性誘發(fā)電位對規(guī)律的破壞都具有較高的敏感性(圖3,5)。最后,在失匹配主效應所在的空間興趣區(qū)內,根據普遍接受的MMN出現的潛伏期區(qū)間(100-250ms),我們提取了僅受失匹配因素影響而不受注意因素影響的波幅(圖6)。綜上所述,這些發(fā)現表明,(1)如同非傷害性觸覺感受失匹配負波一樣,傷害性刺激也可以引發(fā)失匹配大腦響應,但是也不能忽視注意的影響作用。(2)非傷害性觸覺失匹配響應與傷害性感受失匹配響應的頭皮地形圖很相似,但是二者的頭皮地形圖在施加刺激的對側大腦顳葉區(qū)域和同側大腦顳葉區(qū)域的響應起始時間上卻有質的區(qū)別。 實驗二依然是被試內設計,共有兩種注意條件：一種是要求被試將注意集力中在感覺刺激上(積極注意條件active condition),另一種要求被試將注意力從感覺刺激上轉移開(消極注意條件passive condition)。同樣采用巡回范式的設計。與實驗一設計的不同點在于,實驗二中有三種感覺刺激,分別為聽覺刺激,非傷害性觸覺刺激,傷害性感覺刺激。三種感覺模態(tài)(聽覺,非傷害性觸覺,傷害性感受)的刺激呈現在同一block中,且遵守連續(xù)的兩個刺激串不能來自同一感覺模態(tài)的原則,以偽隨機的方式排列三種感覺刺激串。通過三種刺激的感覺模態(tài)的改變作為巡回范式的變量,即每一串刺激中第一個刺激是偏差刺激,始于一種感覺模態(tài)(聽覺,非傷害性觸覺,或傷害性感受),隨著刺激的重復成為標準刺激。該刺激串結束后,進入另一感覺模態(tài)的刺激串的刺激輸出。每個刺激串中有11-15個具有相同物理特性的刺激(來自于同一感覺模態(tài)的相同感覺刺激),刺激間的時間間隔為1000ms,每個刺激串中刺激數目也以偽隨機的方式排布。 實驗二提供了在不同感覺模態(tài)提取失匹配負波有效且可靠的方法,且表明感覺記憶痕的形成以及偏差刺激探測在某種程度上是感覺模態(tài)特異的�？偨Y起來我們主要有四項發(fā)現：(1)不同感覺刺激引發(fā)的失匹配負波響應可以用基于地形圖的分段分析方法來提取。即使在腦電響應中沒有清晰的波峰時,使用這種分析方法也能夠將與失匹配負波功能相關的腦電活動提取出來。(2)三種感覺模態(tài)中的刺激重復兩次后(至少兩次)標準刺激便可以形成(即在第三個刺激位置之后的刺激響應之間差別微小),不論是否注意感覺刺激,也不論刺激串前是何種感覺模態(tài)的刺激串。(3)一旦穩(wěn)定的標準刺激形成后,其后刺激串中的偏差刺激(刺激串中第一個刺激)會受到前面感覺模態(tài)的影響。(4)在同一感覺模態(tài)中,積極注意和消極注意條件下的失匹配負波的波幅有較強的相關關系,而在不同的感覺模態(tài)間這種相關關系并不存在。 本研究通過兩個實驗研究證實了傷害性感受失匹配負波的存在,詳細描述了傷害性感受失匹配負波的潛伏期區(qū)間、波形、頭皮地形圖,并開發(fā)了提取失匹配負波可靠的、高效的方法。又通過對比聽覺以及非傷害性觸覺模態(tài)的MMN腦電響應,進一步探討了失匹配負波內在神經生理學機制。 本研究成功的證實了傷害性感受失匹配負波的存在,填補了在痛覺領域失匹配負波研究的空白,對于失匹配負波在多種感覺通道的研究有補充作用。另外,傷害性感受失匹配負波作為客觀的神經生理學指標,為慢性疼痛患者在非注意情況下的疼痛處理機制研究提供了良好的觀察治療手段,在疼痛的臨床治療方面具有非常重要的意義。
[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.

【學位授予單位】：西南大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：B845

【共引文獻】

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