异氟醚麻醉大鼠介微观尺度上的神经同步分析

Recent data indicate that neural synchrony play an important role in processing neural information. Consciousness and other brain functions require the integration and coordination of activities between brain regions at different scales. The reliable detection and measurement of the neural synchrony is the key to reveal the mechanism of consciousness. Since anesthesia is a robust, reversible and controllable means of inducing transitions in conscious states, which provides an ideal model for the understanding of the mechanism of consciousness. This project focuses on developing novel methods for neural synchronization, analyzing the effect of isoflurane on neural synchrony at micro-mesoscopic scales in rats. An adaptive detection method is first proposed to extract the significant rhythms in local field potentials (LFPs), and the relationship between these oscillations is further explored using wavelet bicoherence and phase-amplitude coupling. Then, based on simulation models and quantitative criteria, an integrated synchrnization index together with a causality index can be proposed and applied to explore the remote synchrony and coupling direction between brain regions, as well as the local synchrony within regions. Furthermore, a new similarity index is developed to quanlify the neuronal synchrony between spike trains, which is sensitive to both bursts and periods of inhibition. The permutation analysis combined with conditional mutual information is applied to quanlify the coupling direction between neurons. Finally, the intermodulation relationship between neural activities at micro-mesoscopic scales is explored through the interaction between LFP and spikes. The development of this project will bulid a novel computational tool for neural synchronization, which will increase our understanding of the mechanism of anesthesia-induced unconsciousness as well as consciousness.

最近研究表明，神经同步是大脑信息处理的重要机制，意识等脑功能是通过多脑区间不同层次的集成和协调来完成的。如何可靠的估计神经振荡的同步特性，是揭示脑意识机制的关键。而麻醉作为一种可逆且可控的改变意识状态的手段，为意识机制研究提供了一个理想的切入点。本项目发展新的同步分析方法，研究异氟醚对大鼠脑介微观尺度上神经同步性的影响。主要包括：以显著节律估计为基础，发展小波双一致和相位幅度耦合方法挖掘不同频率神经振荡间耦合性；利用真实数据建立仿真模型，结合定量准则，发展同步强度和方向性估计方法，分析脑区内/间同步性和耦合方向；提出新的锋序列相似性指数，准确量化同时连续放电或长时抑制时神经元间的同步性，利用排序条件互信息估计神经元间耦合方向；建立局部场电位-锋电位耦合指数，量化介-微观神经活动间的互调关系。项目的开展将提供一新颖的神经同步计算工具，为研究麻醉产生意识消失及意识形成的机制提供有力的技术支撑。

本项目基于神经振荡同步分析，量化麻醉对脑神经活动的影响，研究麻醉产生意识消失的机理问题。发展排序自互信息方法描述麻醉时脑电信号的内在动力学特征；提出综合药代药效动力学模型、预测概率、相关系数等多量化指标的性能评价方法，讨论排序熵参数选取问题，以确定最优的适合临床监控的排序熵指标，同期发表的评论文章称该工作为进一步的开发和临床测试开辟了道路；发展非线性递归图方法检测和量化脑电爆发抑制模式；应用提出的评价方法，对各种熵指标在麻醉深度监测方面的性能进行了系统全面的比较。利用相位随机化和替代数据分析，提出一种更可靠的小波双一致估计方法；在Matlab平台下开发了一包含多种相位幅度耦合量化算法的分析工具包；综合两工具研究麻醉时脑电不同频率神经振荡间的耦合特性，挖掘出不同类型的互调关系。发展排序互信息方法量化麻醉时双通道脑电间的同步性，并将其与多种同步估计方法进行了系统全面的比较；针对多通道皮层脑电信号，提出了S估计器结合一致性的分析方法，揭示了挥发性麻醉药使得大脑皮层毫米尺度上同步性增强现象，同期发表的评论文章称该工作促进了神经同步在意识和麻醉引起的失意中作用的研究。进一步通过分析脑切片上的局部场电位信号的幅度的坡度，揭示麻醉使得大脑皮层亚毫米级尺度上的神经活动同步性增强；提出了加权锋电位场电位相干方法，分析爆发型锋电位序列与局部场电位之间的相关性。另外，合作研发了一简易的单通道近红外光谱系统，为后续的基于脑电-近红外双模态特征研究麻醉时脑活动变化提供工作基础。在基金资助下，共完成论文12篇，其中SCI检索11 篇，完成一脑电频率间互调分析程序包。