痫样棘波自动检测的新算法及其在不同癫痫模型研究中的应用

发布时间：2018-04-01 07:19

本文选题：癫痫模型　切入点：群峰电位　出处：《浙江大学》2017年硕士论文

【摘要】：癫痫发作的典型特征是脑内神经元群体产生异常同步的动作电位发放,在记录的神经电信号中呈现为痫样棘波。在海马区等神经元分布密集之处,于胞体层记录的群峰电位(population spikes,PS)即为棘波。为了定量分析各种不同致痫机理下棘波PS的发放情况,本文设计了一种基于窗口的检测算法,可以自动识别大鼠海马CA1区癫痫模型的棘波信号,同时计算棘波PS的特征参数,并定量分析痫样PS的发放模式,用于探究PS发放模式与致痫机理之间的关系。主要研究结果如下:(1)设计了在原始宽频带记录信号中直接检测棘波PS的算法所设计的棘波PS自动检测新算法,利用拓展窗解决了传统窗口法易于重复检出的问题,同时利用波形的幅值和半高宽等限制指标,提高了检测的正确性。结果表明,在钾离子通道拮抗剂4-氨基吡啶(4-aminopyridine,4-AP)和γ-氨基丁酸A型受体拮抗剂印防己毒素(picrotoxin,PTX)诱导的癫痫模型应用中,该算法的检出率可达94%以上,误检率则小于5%,远小于普通阈值法的误检率。(2)定量分析了 4-AP和PTX两种化学致痫剂诱导的癫痫模型的PS发放模式的差别利用PS幅值、半高宽、发放率和发放时间间隔直方图等参数分析比较4-AP和PTX癫痫模型发作期间痫样棘波串(burst)中的PS特征,结果表明,4-AP诱导的PS具有较宽的波形,发放较分散,发放时间间隔主要分布于100～700 ms范围内。而PTX诱导的PS则呈现爆发式发放,发放率较高,发放时间间隔主要分布于2～20ms范围内,其每秒PS幅值之和显著大于4-AP模型。因此,以痫样棘波PS的发放强度为指标,PTX模型的神经元群体同步发放活动比4-AP模型要强烈。(3)高频电刺激期间神经元PS发放情况分析将棘波PS的自动检测和分析算法应用于大鼠海马CA1区输入轴突通道上顺向高频电刺激(orthodromic high frequency stimulation,OHFS)诱发棘波 PS 的发放。结果表明,OHFS期间PS的发放与刺激频率有关。50 Hz的OHFS会诱发大量痫样PS发放,而100和200 Hz的OHFS则诱发PS较少。进一步分析PS发放的时间间隔及其与刺激脉冲时刻之间的关系,结果显示,OHFS期间的棘波PS可以由刺激脉冲直接诱发产生,也可以由于神经元群体过度兴奋导致的PS多波与burst。另外,在OHFS期间插入短促的间歇期(每隔2 s插入100 ms间歇期),神经元的棘波发放增多,表明间歇期的引入会增强HFS对于下游神经元群体的兴奋作用。总之,本文的棘波PS自动检测新算法及定量分析指标的设计和实现,为正确识别不同癫痫模型中的棘波、评估痫样发放的强度以及定量描述痫样发放的特征提供了有用的工具,对于癫痫产生机理的研究以及癫痫治疗新方法的开发具有重要意义。
[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 纬 -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.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R742.1

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