【作者】 刘迢迢；

【导师】 田心；

【作者基本信息】 天津医科大学 ， 生物医学工程， 2011， 硕士

【摘要】 研究目的：大脑不同模态神经信号的相互协同对工作记忆事件的编码是神经科学、认知科学、信息科学的交叉研究领域之一。本论文研究大鼠在工作记忆任务中,工作记忆责任脑区(前额叶皮层)检测到的两类不同模态的多通道神经信号：连续时间序列形式的多通道局部场电位(Local Field Potentials, LFPs)和离散点电位序列形式的多通道锋电位(Spikes)之间的协同,及其对工作记忆事件的编码。本论文应用LFPs-Spikes的动态频谱相干(Dynamic Spectrum Coherence, DSC)编码方法研究其对工作记忆事件的协同编码模式,为研究工作记忆的神经编码机制提供实验和神经计算的支持。研究方法：1.动物实验实验动物为中国医学科学院放射医学研究所实验动物中心SD大鼠20只(8-10周,300-350g),基于清醒动物在体微电极阵列多通道采集技术,应用cerebus-128在体多通道信号采集系统,记录大鼠在Y迷宫工作记忆任务中前额叶皮层多通道神经信号。1)大鼠Y迷宫工作记忆行为学训练大鼠的工作记忆训练按照国际规范进行：每天训练2次,1次10个训练任务,每个任务包括大鼠对Y迷宫方向的自由选择和反向选择各1次,用秒表计下每次任务开始和完成时间,两次选择间隔5-10s。训练持续进行直到大鼠连续2天工作记忆任务的正确率都大于80%作为学会的标准,即己形成工作记忆。2)在体多通道微电极植入手术大鼠麻醉后固定在立体定位仪上,选择前额叶皮层(以bregma点为参考,向前2.5-4.5mm,旁开0.2-1.0mm)开一个矩形窗口,植入16通道微电极阵列,到达目标脑区颅骨下2.5-3mm后,用牙科水泥固定。术后恢复5-7天,就开始测试。3)采集大鼠在工作记忆任务中前额叶皮层多通道神经信号应用Cerebus-128多通道神经信号在体记录系统记录每只大鼠在Y迷宫工作记忆任务过程中前额叶皮层的多通道神经信号。每次测试记录一个完整的工作记忆任务过程。2.多通道原始数据的预处理对多通道原始记录数据进行低通滤波(0.3-500Hz),获得多通道LFPs。利用加权最小二乘的局部线性回归与拟合方法消除多通道LFPs信号中夹杂的基线漂移与工频干扰,剔除原始数据差分记录中的参考通道和漂移过大通道,获取零均值多通道LFPs,是连续时间序列。对多通道原始记录数据进行高通滤波(500-7500Hz),再经过锋电位检测和离线除噪,得到多通道Spikes,是离散点电位形式,离散时间序列。3.多通道LFPs-Spikes的动态频谱相干编码1)离散“点电位”的连续化因为动态频谱相干编码适用于连续信号,而多通道Spikes中每一个通道的Spikes序列是离散的“点电位”,因此本论文的首先将离散Spikes的“点电位”通过神经元频率编码的方式转换为连续信号。选取生理窗口窗宽500ms、窗口移动步长为125ms,从初始点开始,计算行为事件参考点前后每通道每个窗口内平均发放率｛r(t)｝,,并且进行频率编码和计算其平均发放个数。2)多通道LFPs和Spikes的配对基于微电极阵列的物理顺序,将数据预处理后的每一根电极对应的LFPs和连续化后的Spikes,进行配对,得到多通道LFPs-Spikes数据对。3)多通道LFPs-Spikes动态频谱相干编码选取生理窗口500ms,移动步长为125ms,从初始点开始逐个应用离散正交扁球序列(Discrete Prolate Spheroidal Sequences, DPSS)对单通道LFPs-Spikes序列加窗,计算每个滑动窗口内单通道LFPs-Spikes数据对的频谱相干值,进而计算多通道LFPs-Spikes的动态频谱相干值。结果：1.大鼠在Y迷宫的工作记忆行为学训练结果20只大鼠中17只在Y迷宫中工作记忆任务正确率随着训练次数的增多而提高,训练10天之后正确率都保持在80%以上。其余3只大鼠因不能适应Y迷宫环境及花生气味无法完成工作记忆任务而剔除。2.大鼠在Y迷宫工作记忆任务中多通道原始数据对17只训练成功的大鼠前额叶皮层进行在体多通道微电极阵列植入手术,记录大鼠在Y迷宫中完成工作记忆任务时多通道神经信号。1)同时记录到LFPs和Spikes并且通道数大于12的大鼠共2只,完成工作记忆任务超过百次：1号大鼠14通道,2号大鼠15通道；3号-6号分别有5,5,6,7通道；2)仅记录到LFPs的大鼠5只,仅记录到Spikes的大鼠4只,这9只大鼠因无法完成LFPs和Spieks的配对而剔除；3)其余2只大鼠没有记录到LFPs和Spikes而剔除。本论文选择1号和2号大鼠的典型结果各10次,选取10s(工作记忆事件参考点前后5s)作为主要研究对象。3.多通道LFPs-Spikes的动态频谱相干编码1)多通道LFPs的频谱编码：多通道LFPs频谱地形图显示,多通道LFPs的能量主要分布在0.3-15Hz。2)多通道Spikes频率编码：多通道Spikes频率编码地形图显示,多通道Spikes的平均放电率峰值出现在第2-4s。3)多通道LFPs-Spikes的频谱相干编码1号大鼠10次重复工作记忆任务中,多通道LFPs-Spikes在第2-4s,0.3-15Hz的频谱相干值(0.6507±0.012)与其他时间和频率频谱相干值(0.3182±0.0265),经t检验,有统计学差别(P<0.05)。2号大鼠10次重复工作记忆任务中,多通道LFPs-Spikes在第2-4s,0.3-15Hz的频谱相干值(0.6541±0.0071)与其他时间和频率频谱相干值(0.3248±0.0061),经t检验,有统计学差别(P<0.05)。结论：本论文研究了大鼠Y迷宫工作记忆行为过程中的多通道神经信号,研究多通道LFPs-Spikes的动态频谱相干对工作记忆事件的编码,研究结果表明：1.大鼠前额叶皮层的多通道LFPs-Spikes在第2-4s,0.3-15Hz的频谱相干值明显高于其他时间(P<0.05),表明不同模态的多通道神经信号在第2-4s,0.3-15Hz发生了固定相位的振荡,有效地编码工作记忆事件；并且在工作记忆时间参考点(第5s)之前,预测了工作记忆事件。2.多通道LFPs-Spikes的动态频谱相干编码从两种不同模态神经信号协同角度,与慢时间尺度连续的多通道LFPs频谱编码和快时间尺度离散的多通道Spikes频率编码对工作记忆事件的编码互补。更多还原

【Abstract】 ObjectiveWorking memory in brain is coded by different modal neural signals collaboratively, which is crossover study of neuroscience, cognitive science, information science area. This thesis study on working memory task in rats brain (prefrontal cortex) in vivo multichannel neural signals of two different modes: continuous time series form of multi-channel local field potentials (LFPs), discrete points of multi channel Spike (Spikes), and its code on working memory events. Papers of LFPs-Spikes dynamic spectrum coherent (DSC) coding method for its collaborative coding mode of working memory events, supporting for the study of Animal experiments and neural coding mechanisms of working memory.Methods1. Animal experimentsExperimental animals from the Chinese Academy of Medical Sciences Institute of radiation medicine experimental animal Center are SD rats 20. Base on rats in vivo multi-channel micro-electrode array acquisition techniques, use Cerebus-128 neural signal process system, recorde 16-channel neural signals in rat prefrontal cortex in Y-maze during working memory tasks.1) Rats working memory task training in Y-mazeWorking memory training in accordance with the specification at home and abroad:train 2 times a day,1 times 10 task, one task includes one free choice and one invert selection on the direction of Y-maze, timing task completion times using the stopwatch, two choice interval 5-10s. Training continued until the rat consecutive 2 days the correct rate of working memory task is greater than 80%, which had already been formed working memory.2) Multi-channel micro-electrode implantation in vivoFixed in rats after anesthesia on stereotaxic instrument, select the prefrontal cortex (2.5-4.5mm anterior to bragma and 0.2-1.0mm lateral to midline) opened a rectangular window, implanted 16 micro-electrode array, when it reaches the target depth 2.5-3mm deep from cortical surface, with dental cement. Postoperative recovery for 5-7 days.3) Collect multi-channel neural signals in working memory task of ratsApplication Cerebus-128 multi-channel neural signal process system records 16 channel neural signals in rats of prefrontal cortex in vivo during working memory tasks in Y-maze. Each test records several complete working memory tasks.2. Multi-channel raw data pre-processingMulti-channel LFPs were acquired through lowpass filtering the raw data (0.3-500Hz). Local linear regression based on the weighted least square method was used to remove the baseline drift and power-line interference on LFPs. Get zero mean multi-channel LFPs, are continuous time series.Multi-channel Spikes were acquired through high pass filtering the raw data (500-7500Hz), spike detecting and offline denoising, which are the discrete points of potential forms, discrete-time sequence.3. Multi-channel LFPs-Spikes dynamic Spectrum coherence coding1) Discrete points continuedBecause dynamic spectrum coherence coding applied to continuous signals and each channel sequences of Spikes are discrete points, this paper discrete Spikes converts continuous signals through neurons of frequency coding firstly. Select physiology window width 500ms, window step is 125ms, starting from the initial point, calculate average rate per channel each window {r(t)}i, and frequency-coding.2) Pairs of multi-channel LFPs and multi-channel SpikesAfter preprocess of the raw data, based on the physical order of the micro-electrode array, each channel LFPs corresponds to the Spikes, get multi-channel LFPs-Spikes data pairs.3) Dynamic spectrum coherence coding of multi-channel LFPs-SpikesSelect the physiology Windows is 500ms, moving step is 125ms, individually from the initial point of Discrete Prolate Spheroidal Sequences (DPSS) on multi-channel window LFPs-Spikes sequence, calculat for each single channel LFPs-Spikes data on sliding window spectrum coherent value and further cmpute dynamic spectrum coherent values of multichannel LFPs-Spikes. Results1. Working memory training results of rats in Y-mazeThe correct of 17 rats working memory task in a Y-maze increase with the number of training, after 10 days the correct of 17 rats is maintained at more than 80%. Remaining 3 rats who cannot adapt to the Y-maze environment and peanut odor hade been completed excluded.2. Multi-channel raw data of rats in a working memory task in Y-mazeBecause of rats in vivo implantation and record multichannel microelectrode array completed in Y-maze, while recording to LFPs and Spikes of rat 2 over dust-ups tasks:lth 14 channels LFPs and Spikes,2th 15 channel LFPs and Spikes.3th-6th 5,5,6,7channnels. Only LFPs are 5 rats; Only Spikes are 4 rats. Choose to record this thesis to LFPs and Spikes typical of the rats 2 results 10 times, select 10s (working memory before and after the event reference point 5s) as a research object.3. Multiple channel LFPs-Spikes dynamic spectrum coherence coding1) spectrum maps of multichannel LFPs show, the energy are mainly distributed in 0.3-15Hz.2) multi-channel frequency encoding map shows that average discharge rate of multichannel Spikes peak occurred in 2-4s.3)lth rat, repeated 10 times in working memory task, in 2-4s,0.3-15Hz of spectrum coherent values (0.6507±0.012) and other time and frequency spectrum coherent values (0.3182±0.0265), thoug the t test, there are statistical differences (P<0.05).2nd rat repeat 10 times in working memory task, in 2-4s,0.3-15Hz of spectrum coherent values (0.6541±0.0071) and other time and frequency spectrum coherent values (0.3248±0.0061), though the t test, there are statistical differences (P＜0.05).ConclusionsThis thesis study multichannel neural signals of rats (prefrontal cortex) during work and memory in Y-maze, research on multichannel dynamic coherence on working memory of the LFPs-Spikes event code, study results show that:1. Multi-channel in rat prefrontal cortex LFPs-Spikes dynamic spectrum coherece codes memory events effectively:2-4s,0.3-15Hz of spectrum coherent value significantly higher than the other times and frequency (P<0.05), and before the working memory of the time reference point (5s), predicts working memory events.2. Dynamic spectrum coherence of multi-channel LFPs-Spikes from two different modal collaborative perspects encodes working memory events, with supplement of single-mode multi-channel LFPs dynamic spectrum encoding and multi-channel complementary Spikes frequency coding.更多还原