神经工程与脑-机接口

神经工程是近年来在生物医学工程领域备受关注的学科发展新方向。它运用神经科学和工程学的方法来分析神经功能并为神经功能缺失与紊乱的修复提供新的解决问题的方案;而脑-机接口则是当前神经工程领域中最活跃的研究方向之一。脑-机接口是在脑与计算机或其他外部设备之间建立的直接的通信和交流通道。在脑-机接口系统中,具有特定模式的脑信号携带着受试者希望表达的意愿,计算机将接收到的脑信号转换成相应的控制命令,于是那些有运动障碍的残疾人就可以利用脑-机接口系统来实现与外界的交流与对外部设备的控制。在基于脑电信号的脑-机接口系统中,受试者产生的脑信号大致可以分为内源性（endogenous）和外源性（exogenous）两类。其中外源性的成分主要取决于外部物理刺激（视觉、听觉或触觉）的参数而与认知行为无关;而内源性成分则主要由认知行为产生而与外部的物理刺激无关。在许多情况下,脑－机接口中的瞬态诱发电位通常都同时包含着内源性和外源性两种成分。寻找新的脑－机接口模式使之能显著提升记录脑电信号中的内源性与外源性成分在脑－机接口研究中具有重要意义。本文中将介绍一种基于运动起始时刻（motion—onset）的新的脑-机接口实验范式。本文的最后还探讨了脑－机接口未来发展的趋势与展望。     

可检测脑不同部位功能的新医学图像仪MSI

美国加里福尼亚Scripps研究所和新墨西哥大学医学院及退伍军人管理局医学中心合研制成一种新的医学成像像技术—磁源成像(Magnetic Source Imaging,MSI)系统。MSI是一种追踪人体内微弱的生物电信号的技术。无论是脑还是肌肉组织在正常动时都会发出电信号。例如,当一位接受MSI检查的患者动一个手指,他头上的MSI探测器就能测出脑部发出的导致该动作的电信号。与现在所有检测技术不同的是,MSI扫描图不仅能显示脑的结构,尚能标明脑的不同部位的功能。而计算机x线断层(CT)或磁共振     

昆虫嗅觉系统结构与功能研究进展

昆虫的脑由前脑、中脑和后脑组成,其中前脑含有高级感觉中枢,如蘑菇体和中央复合体,控制昆虫的学习、记忆和运动等高级神经活动;中脑包含触角叶,是嗅觉神经中心;而后脑则通常不发达,主要包括内分泌神经元和控制进食与消化的运动神经元。不同于其他物种,昆虫由于其特殊的生活习性,听觉和视觉系统相对退化,主要依赖嗅觉来捕食、交流和求偶,因此嗅觉系统尤其发达。本文综述了目前对昆虫的脑部主要神经结构和功能(中央复合体、蕈形体和触角叶结构)以及昆虫脑部结构遗传变异(性别异构,不同发育时期、不同昆虫以及昆虫与其他动物的脑部结构差异)的研究进展,并总结了目前昆虫脑对信号的加工处理和识别机制的研究结果。     

微生物学计算机网络化辅助教学探索*

随着计算机的网络化发展 ,上网已成为人类生活不可分隔的部分。通过个人电脑不仅可以直接上网获得所需的信息和资料 ,也可以进行一些网络远程教育等信息交流活动。基于这样一种计算机发展趋势 ,我们近几年一直进行着网络化计算机辅助微生物教学的尝试 ,以现代化的技术手段来改革微生物教学手段和方法以适应时代发展。目前国内不少高校也在尝试这种改革 ,如武汉大学在校园网上建立微生物学专题网页 ,为学生提供了一些教材外的知识和图片资料 ,如微生物学发展历史和最新前沿进展等。本文提供我单位近几年在微生物学导师系统的网络化辅助教学方…     

日本三角涡虫神经系统的组织学观察

为了给涡虫神经生物学的比较研究提供基础资料和通过RNAi技术为研究与脑部再生有关基因的功能奠定基础,本研究使用石蜡连续切片技术,经HE和Masson染色后,对日本三角涡虫Dugesia japonica的神经系统进行观察.日本三角涡虫的中枢神经系统由脑和2条纵神经索组成,脑呈马蹄形;纵神经索从头部到尾部逐渐变细;脑部神经细胞突起连接成网状,纵神经索内神经细胞突起呈纵向排列;咽壁神经组织排列成内外2个圆筒状.这些结构差异反映出日本三角涡虫在涡虫纲系统演化中处于较高级的地位.     

脑部基因疗法的新载体

美国Oregon Health Sciences University的研究人员设计了一种可将基因送入脑部以治疗退化性神经系统疾病的人造载体。以前曾进行过用逆转录病毒基因疗法治疗脑瘤的尝试。但是,由于神经退化性疾病的目标细胞是不能分裂的神经元,故而需要一种替代性方法以弥补逆转录病毒不能对非分裂细胞起作用的缺陷。由Edward领导的这一研究小组开发了一种由直径100纳米的病毒大小氧化铁晶体构成的人造载体。晶体上包被了称为右旋糖酐的糖样物质。目前只用“空”载体测定了该晶体在脑中的特性。为了确保注入的氧化铁颗粒到达脑部,使用了一种可打破血脑屏障的药品。由于氧化铁颗粒有磁性,所以可用     

骨源活性物质的中枢调控功能

骨是机体的主要支持结构,也是参与机体运动和钙磷代谢的主要器官.骨也是一种潜在的新型内分泌器官,其通过骨细胞和骨髓分泌的多种生物活性物质,参与心血管、消化、内分泌等多个系统的生理和病理生理过程.骨源活性物质还可直接作用于中枢神经系统,参与脑功能和个体行为的调节,骨-脑轴的双向调控也逐渐引起了神经科学研究领域的关注.本文综...     

脑靶向寡核苷酸药物策略用于衰老相关脑部疾病治疗

寡核苷酸药物近10年发展迅速,已有多款应用于临床治疗。因其设计便捷、序列灵活、特异性高,有望解决许多靶点难成药的困境,并且其临床转化周期和成本较低,目前已成为新兴生物技术药物研发的前沿领域。脑部疾病包括多种目前无法治愈的疾病,如神经退行性疾病、胶质瘤、运动神经元疾病等,其中很多与年龄相关,被认为是衰老相关脑部疾病。因其病因复杂,许多靶点难成以药,同时由于脑部特殊屏障系统“血脑屏障”的存在,导致大部分药物无法实现脑部病灶的有效积累,众多小分子药物遭遇临床转化失败。寡核苷酸类药物的特异性和序列灵活性提供了新的成药可能性,但同样面临脑部递送的挑战。尽管目前已有多款寡核苷酸类药物应用于医疗市场,但脑靶向寡核苷酸药物仍然极为罕见,随着纳米递送和脑靶向基团研究的逐渐成熟,未来5~10年寡核苷酸药物用于脑部疾病治疗将成为可能。本文针对本领域重点话题如寡核苷酸药物临床批准的应用案例、脑靶向寡核苷酸药物的递送瓶颈和当前策略,以及衰老相关脑部疾病的寡核苷酸药物潜在靶点进行了梳理,同时对临床转化中的难点和面临的挑战展开了综述和讨论。     

基于多特征融合的多分类运动想象脑电信号识别研究

针对目前多分类运动想象脑电识别存在特征提取单一、分类准确率低等问题,提出一种多特征融合的四分类运动想象脑电识别方法来提高识别率。对预处理后的脑电信号分别使用希尔伯特-黄变换、一对多共空间模式、近似熵、模糊熵、样本熵提取结合时频—空域—非线性动力学的初始特征向量,用主成分分析降维,最后使用粒子群优化支持向量机分类。该算法通过对国际标准数据集BCI2005 Data set IIIa中的k3b受试者数据经MATLAB仿真处理后获得93.30%的识别率,均高于单一特征和其它组合特征下的识别率。分别对四名实验者实验采集运动想象脑电数据,使用本研究提出的方法处理获得了72.96%的平均识别率。结果表明多特征融合的特征提取方法能更好的表征运动想象脑电信号,使用粒子群支持向量机可取得较高的识别准确率,为人脑的认知活动提供了一种新的识别方法。     

微透析技术在脑靶向中应用

微透析技术作为一门新兴的技术,近年来多用于靶向分布和体内代谢等方面,尤其是在药物的脑部研究方面,该技术显得尤为重要。如今,随着新型探针的不断出现,以及微量、快速、灵敏的分析检测手段的发展,微透析技术已日益成为药物脑部研究的重要工具。现通过检索近十年来的相关文献,对脑微透析技术的概况、原理、脑微透析探针以及其应用作一综述,希望能为从事该方面研究的药学工作者提供相关参考。     

Method for testing motion analysis laboratory measurement systems

This paper proposes a method for comparing data from accelerometers, optical based 3D motion capture systems, and force platforms (FPs) in the context of spatial and temporal differences. Testing method is based on the motion laboratory accreditation test (MLAT), which can be used to test FP and camera based motion capture components of a motion analysis laboratory. This study extends MLAT to include accelerometer data. Accelerometers were attached to a device similar to the MLAT rod. The elevation of the rod from the plane of the floor is computed and compared with the force platform vector orientation and the rod orientation obtained by optical motion capture system. Orientation of the test device is achieved by forming nonlinear equation group, which describes the components of the measured accelerations. Solution for this equation group is estimated by using the Gauss-Newton method. This expanded MLAT procedure can be used in the laboratory setting were either FP, camera based motion capture, or any other motion capture system is used along with accelerometer measurements.     

Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System

The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced in blood banking facilities where staff can supervise automated protocols to produce multiple products.     

Predictive motor activation during action observation in human infants

Certain regions of the human brain are activated both during action execution and action observation. This so-called ‘mirror neuron system’ has been proposed to enable an observer to understand an action through a process of internal motor simulation. Although there has been much speculation about the existence of such a system from early in life, to date there is little direct evidence that young infants recruit brain areas involved in action production during action observation. To address this question, we identified the individual frequency range in which sensorimotor alpha-band activity was attenuated in nine-month-old infants'' electroencephalographs (EEGs) during elicited reaching for objects, and measured whether activity in this frequency range was also modulated by observing others'' actions. We found that observing a grasping action resulted in motor activation in the infant brain, but that this activity began prior to observation of the action, once it could be anticipated. These results demonstrate not only that infants, like adults, display overlapping neural activity during execution and observation of actions, but that this activation, rather than being directly induced by the visual input, is driven by infants'' understanding of a forthcoming action. These results provide support for theories implicating the motor system in action prediction.     

Memory trace in prefrontal cortex: theory for the cognitive switch

The dorsolateral prefrontal cortex in human and non-human primates functions as the highest-order executor for the perception-action cycle. According to this view, when perceptual stimuli from the environment are novel or complex, the dorsolateral prefrontal cortex serves to set consciously a goal-directed scheme which broadly determines an action repertory to meet the particular demand from the environment. In this respect, the dorsolateral prefrontal cortex is a short-term activation device with the properties of a cognitive switch', because it couples a particular set of perceptual stimuli to a particular set of actions. Here, I suggest that, in order for the organism to react systematically to the environment, neural traces for the switch function must be stored in the brain. Thus, the highest-order, perception-action interface function of the dorsolateral prefrontal cortex per se depends on permanently stored neural traces in the dorsolateral prefrontal cortex and related structures. Such a memory system may be located functionally between two of the well-documented memory systems in the brain: the declarative memory system and the procedural memory system. Finally, based on available neurophysiological data, the possible mechanisms underlying the formation of cognitive switch traces are proposed.     

Screening algal mutant colonies with altered thylakoid electrochemical gradient through fluorescence and delayed luminescence digital imaging

A digital imaging instrument intended to monitor fluorescence and delayed luminescence of algal colonies grown on Petri plates is described. The system includes light-emitting diodes, a cooled line transfer charge-coupled device (CCD) camera, and a personal computer. Software developments were made to capture pictures and kinetics in real time during illuminations. This instrument makes the fluorescence induction kinetics of individual colonies readily accessible with a good time resolution. It offers a great refinement for screening colonies deficient in photosynthetic electron transfer thanks to appropriate computed fluorescence images. The high sensitivity of the instrument allows it to capture fluorescence images under non-actinic illuminations, and for the first time, delayed luminescence images, opening thus the way to screening mutants that have altered thylakoid electrochemical gradients.     

Rapid isolation of viable circulating tumor cells from patient blood samples

Circulating tumor cells (CTC) are cells that disseminate from a primary tumor throughout the circulatory system and that can ultimately form secondary tumors at distant sites. CTC count can be used to follow disease progression based on the correlation between CTC concentration in blood and disease severity. As a treatment tool, CTC could be studied in the laboratory to develop personalized therapies. To this end, CTC isolation must cause no cellular damage, and contamination by other cell types, particularly leukocytes, must be avoided as much as possible. Many of the current techniques, including the sole FDA-approved device for CTC enumeration, destroy CTC as part of the isolation process (for more information see Ref. 2). A microfluidic device to capture viable CTC is described, consisting of a surface functionalized with E-selectin glycoprotein in addition to antibodies against epithelial markers. To enhance device performance a nanoparticle coating was applied consisting of halloysite nanotubes, an aluminosilicate nanoparticle harvested from clay. The E-selectin molecules provide a means to capture fast moving CTC that are pumped through the device, lending an advantage over alternative microfluidic devices wherein longer processing times are necessary to provide target cells with sufficient time to interact with a surface. The antibodies to epithelial targets provide CTC-specificity to the device, as well as provide a readily adjustable parameter to tune isolation. Finally, the halloysite nanotube coating allows significantly enhanced isolation compared to other techniques by helping to capture fast moving cells, providing increased surface area for protein adsorption, and repelling contaminating leukocytes. This device is produced by a straightforward technique using off-the-shelf materials, and has been successfully used to capture cancer cells from the blood of metastatic cancer patients. Captured cells are maintained for up to 15 days in culture following isolation, and these samples typically consist of >50% viable primary cancer cells from each patient. This device has been used to capture viable CTC from both diluted whole blood and buffy coat samples. Ultimately, we present a technique with functionality in a clinical setting to develop personalized cancer therapies.     

昆虫飞行速度和持续时间监测仪硬件设计

本文设计了利用微机记录昆虫飞行状态的实验装置,这种装置由两部分组成,一部分是设计和制作一个飞行磨供昆虫飞行,另一部分是制作光电传感器和微机检测系统,记录信号并把信号进行识别、分析、归类,送往计算机显示和打印。介绍了其工作原理和使用方法。     

A computational model for the primate neocortex based on its functional architecture

Experimental evidence has shown that the primate neocortex consists in the main of a set of cortical regions which form a perception hierarchy, an action hierarchy and connections between them. By using a computer science analysis, we develop a computational architecture for the brain in which each cortical region is represented by a computational module with processing and storage abilities. Modules are interconnected according to the connectivity of the corresponding cortical regions. We develop computational principles for designing such a hierarchical and parallel computing system. We demonstrate this approach by proposing a causal functioning model of the brain. We report on results obtained with an implementation of this model. We conclude with a brief discussion of some consequences and predictions of our work.     

神经元信息编码的代谢消耗：动作电位与能量效率

人脑是一个高效、可靠的信息处理系统,它主导着个体的认知、情感、意识与行为,这些功能的实现需要不断地消耗代谢能量.大脑的能量需求主要被神经元信息编码所消耗,相应的亚细胞过程包括产生和传导动作电位、维持静息电位以及突触传递.神经元编码信息的主要载体是动作电位序列,它的产生与传导贡献了大脑的大部分代谢消耗.动作电位的能量消耗受离子通道的生物物理特性控制.生物物理特性的细胞特异性和空间异质性使得动作电位对代谢能量的利用效率呈现高度可变性,它为理解神经元代谢消耗的规律、起因与结果带来了挑战.本文首先介绍参与神经元编码的亚细胞过程及它们在大脑和小脑皮层中的代谢消耗,然后详细梳理近年来关于动作电位代谢消耗的研究成果,重点讨论影响其能量效率的生物物理因素和放电形状特性,并归纳总结放电消耗的特点,最后对未来神经元编码的代谢消耗研究进行展望.