本文選題：癲癇模型　切入點(diǎn)：群峰電位　出處：《浙江大學(xué)》2017年碩士論文

【摘要】：癲癇發(fā)作的典型特征是腦內(nèi)神經(jīng)元群體產(chǎn)生異常同步的動(dòng)作電位發(fā)放,在記錄的神經(jīng)電信號(hào)中呈現(xiàn)為癇樣棘波。在海馬區(qū)等神經(jīng)元分布密集之處,于胞體層記錄的群峰電位(population spikes,PS)即為棘波。為了定量分析各種不同致癇機(jī)理下棘波PS的發(fā)放情況,本文設(shè)計(jì)了一種基于窗口的檢測(cè)算法,可以自動(dòng)識(shí)別大鼠海馬CA1區(qū)癲癇模型的棘波信號(hào),同時(shí)計(jì)算棘波PS的特征參數(shù),并定量分析癇樣PS的發(fā)放模式,用于探究PS發(fā)放模式與致癇機(jī)理之間的關(guān)系。主要研究結(jié)果如下:(1)設(shè)計(jì)了在原始寬頻帶記錄信號(hào)中直接檢測(cè)棘波PS的算法所設(shè)計(jì)的棘波PS自動(dòng)檢測(cè)新算法,利用拓展窗解決了傳統(tǒng)窗口法易于重復(fù)檢出的問(wèn)題,同時(shí)利用波形的幅值和半高寬等限制指標(biāo),提高了檢測(cè)的正確性。結(jié)果表明,在鉀離子通道拮抗劑4-氨基吡啶(4-aminopyridine,4-AP)和γ-氨基丁酸A型受體拮抗劑印防己毒素(picrotoxin,PTX)誘導(dǎo)的癲癇模型應(yīng)用中,該算法的檢出率可達(dá)94%以上,誤檢率則小于5%,遠(yuǎn)小于普通閾值法的誤檢率。(2)定量分析了 4-AP和PTX兩種化學(xué)致癇劑誘導(dǎo)的癲癇模型的PS發(fā)放模式的差別利用PS幅值、半高寬、發(fā)放率和發(fā)放時(shí)間間隔直方圖等參數(shù)分析比較4-AP和PTX癲癇模型發(fā)作期間癇樣棘波串(burst)中的PS特征,結(jié)果表明,4-AP誘導(dǎo)的PS具有較寬的波形,發(fā)放較分散,發(fā)放時(shí)間間隔主要分布于100～700 ms范圍內(nèi)。而PTX誘導(dǎo)的PS則呈現(xiàn)爆發(fā)式發(fā)放,發(fā)放率較高,發(fā)放時(shí)間間隔主要分布于2～20ms范圍內(nèi),其每秒PS幅值之和顯著大于4-AP模型。因此,以癇樣棘波PS的發(fā)放強(qiáng)度為指標(biāo),PTX模型的神經(jīng)元群體同步發(fā)放活動(dòng)比4-AP模型要強(qiáng)烈。(3)高頻電刺激期間神經(jīng)元PS發(fā)放情況分析將棘波PS的自動(dòng)檢測(cè)和分析算法應(yīng)用于大鼠海馬CA1區(qū)輸入軸突通道上順向高頻電刺激(orthodromic high frequency stimulation,OHFS)誘發(fā)棘波 PS 的發(fā)放。結(jié)果表明,OHFS期間PS的發(fā)放與刺激頻率有關(guān)。50 Hz的OHFS會(huì)誘發(fā)大量癇樣PS發(fā)放,而100和200 Hz的OHFS則誘發(fā)PS較少。進(jìn)一步分析PS發(fā)放的時(shí)間間隔及其與刺激脈沖時(shí)刻之間的關(guān)系,結(jié)果顯示,OHFS期間的棘波PS可以由刺激脈沖直接誘發(fā)產(chǎn)生,也可以由于神經(jīng)元群體過(guò)度興奮導(dǎo)致的PS多波與burst。另外,在OHFS期間插入短促的間歇期(每隔2 s插入100 ms間歇期),神經(jīng)元的棘波發(fā)放增多,表明間歇期的引入會(huì)增強(qiáng)HFS對(duì)于下游神經(jīng)元群體的興奮作用�？傊�,本文的棘波PS自動(dòng)檢測(cè)新算法及定量分析指標(biāo)的設(shè)計(jì)和實(shí)現(xiàn),為正確識(shí)別不同癲癇模型中的棘波、評(píng)估癇樣發(fā)放的強(qiáng)度以及定量描述癇樣發(fā)放的特征提供了有用的工具,對(duì)于癲癇產(chǎn)生機(jī)理的研究以及癲癇治療新方法的開(kāi)發(fā)具有重要意義。
[Abstract]:The typical feature of epileptic seizures is that the neurons in the brain produce abnormal synchronous action potential (APP) and present epileptiform spikes in the recorded neuroelectric signals.Where neurons are densely distributed in the hippocampal area, the population spikes-PSs recorded in the somatic layer are spike waves.In order to quantitatively analyze the release of spike PS under various epileptic mechanisms, a window-based detection algorithm was designed to automatically recognize spike signals of rat hippocampal CA1 epileptic model and calculate the characteristic parameters of spike PS.And quantitative analysis of epileptiform PS distribution model to explore the relationship between the distribution model and the mechanism of epilepsy.The main results are as follows: (1) A new algorithm for detecting spike PS directly in the original broadband recording signal is designed. The extended window is used to solve the problem that the traditional window method is easy to repeat detection.At the same time, the validity of the detection is improved by using the limited indexes such as amplitude and half maximum width of the waveform.The results showed that the detection rate of this algorithm was more than 94% in the epileptic model induced by potassium channel antagonist 4-aminopyridine 4-APand 緯 -aminobutyric acid A receptor antagonist, Tetrandrine picrotoxin PTX.The false detection rate was less than 5, much less than that of the ordinary threshold method.) the difference of PS release pattern between 4-AP and PTX induced epilepsy model was analyzed quantitatively by using PS amplitude and half maximum width.The distribution rate and distribution interval histogram were analyzed to compare the PS characteristics of epileptiform spike burst in 4-AP and PTX epileptic models. The results showed that PS induced by 4-AP had a wide waveform and distributed distribution.The distribution interval was mainly distributed in the range of 100m ~ 700ms.However, the PS induced by PTX showed explosive distribution, and the distribution time interval was mainly distributed in the range of 2~20ms, and the sum of PS amplitude per second was significantly larger than that of 4-AP model.Therefore,Using the intensity of epileptiform spike PS as an index, the synchronous distribution activity of neuron population in PTX-model is stronger than that in 4-AP model.) during high frequency electric stimulation, the analysis of the distribution of PS in neurons will apply the automatic detection and analysis algorithm of spike PS.Orthodromic high frequency stimulation (OHFSs) on the input axon channel of rat hippocampal CA1 region induced spike PS emission.The results showed that during OHFS, the release of PS was related to the frequency of stimulation. OHFS with 50 Hz could induce a large number of epileptiform PS emissions, while OHFS at 100 Hz and 200 Hz could induce less PS.The relationship between the time interval of PS release and the time of stimulus pulse was further analyzed. The results showed that the spike PS during OHFS could be induced directly by the stimulus pulse, or the PS multiwave and burstas caused by the excitability of the neuron population.In addition, the insertion of short intermission (100ms interval every 2 s) during OHFS increased the spike release of neurons, which indicated that the introduction of intermission increased the excitatory effect of HFS on the downstream neuronal population.In a word, the new algorithm of PS automatic detection and the design and implementation of quantitative analysis index provide a useful tool for correctly identifying spike waves in different epileptic models, evaluating the intensity of epileptiform distribution and quantitatively describing the characteristics of epileptiform distribution.It is of great significance for the study of the mechanism of epilepsy and the development of new methods for the treatment of epilepsy.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R742.1

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