用于功能性胃肠疾病治疗的植入式电刺激系统及动物实验研究

目的研究可用于功能性胃肠疾病治疗的植入式电刺激系统,通过动物实验研究,探讨不同刺激参数对胃肠道收缩活动的作用效果,为治疗用刺激参数的优化提供初步依据。方法系统由便携式体外控制器和植入式体内刺激器组成,体内外通信采用无线模式。刺激脉冲参数及指令由体外控制器设定并发送至体内刺激器,胃肠道收缩活动由体内刺激器集成的压力检测模块采集并发送至体外以供分析。通过电刺激猪盲肠实验,分析不同刺激参数下盲肠压力的变化,以评价刺激参数对盲肠收缩活动的作用效果。结果系统样机工作正常,输出刺激脉冲信号精确,压力信息记录准确。动物实验表明,增加刺激脉冲宽度使盲肠收缩活动的幅度增大,增加刺激脉冲频率使盲肠收缩活动的潜伏期缩短,增加刺激脉冲幅度同时缩短盲肠收缩活动的潜伏期并增大收缩幅度。结论该植入式电刺激系统参数设定范围大,输出脉冲信号精确并具备压力检测功能,便于进行功能性胃肠疾病治疗刺激参数的筛选和验证。动物实验初步验证了不同刺激参数对盲肠收缩活动的作用效果。     

低等哺乳动物的学习行为训练系统的研制

目的针对缺乏适应于低等哺乳动物条件反射与辨别学习行为的综合训练平台问题,本文设计并构建了一套适用于训练低等哺乳动物建立行为模型的自动训练系统。方法系统包括信号刺激与信号采集分析两大部分：刺激子系统产生条件刺激与非条件刺激信号训练刺激动物;信号采集分析子系统则以专用的生物信号采集装置采集动物的眨眼行为信号与脑电信号,记录并分析动物在条件刺激与非条件刺激下的眨眼行为信号与脑电信号。实验以豚鼠作为研究对象,分组进行条件刺激与非条件刺激配对实验。结果实验结果表明,通过对脑电信号的分析可以准确区分和判定豚鼠对特定声音的反应。豚鼠经过该系统的训练,形成了条件反射与辨别学习能力。结论该系统的成功设计为大脑神经活动和行为之间的相关性研究提供了实验平台。     

不同电极电刺激对有髓神经传导阻断影响的仿真研究

目的 比较双电极双向脉冲刺激和单电极双向脉冲刺激在神经纤维传导阻断中的阻断阈值以及对神经纤维的损伤,并通过该研究为电刺激促进脊髓损伤后下尿路功能重建的动物实验选择最优的刺激模式.方法 以有限长单根有髓神经为研究对象,以两栖动物的有髓神经纤维FrankenhaeuserHuxley（F-H）模型为仿真研究基础.结果 比较了单、双电极在双向对称方波以及双向间歇方波作用下的阻断阈值以及单双电极在同样的刺激条件下（包括刺激波形、频率以及电流强度）产生的离子电流强度大小.结论 双电极的阻断阈值大于单电极的阻断阈值.在相同的刺激条件下,双电极双向脉冲刺激对神经的损伤程度小于单电极双向脉冲刺激.     

低频电刺激对脊髓损伤后膀胱过度活动抑制的仿真研究

目的 探讨低频脉冲（0～10Hz）刺激时,不同刺激波形对脊髓损伤后逼尿肌反射亢进诱发的膀胱过度活动症的结果,以寻求抑制膀胱过度活动的最优刺激波形.方法 首先根据McNeal的神经纤维电缆模型,基于Frankenhaeuser-Huxley （FH） 方程建立有髓神经纤维的膜外点电极刺激的仿真系统,评价低频电刺激中的四种波形,即正向脉冲、负向脉冲、双向对称脉冲、双向不对称脉冲的效果.通过电刺激脊髓损伤犬的阴部神经实验,验证仿真条件下最优刺激波形的临床效果.结果 仿真实验表明双向不对称脉冲的抑制效果最佳;动物实验表明以3V、0.1ms的正向脉冲为起始脉冲,结合1V、0.3ms的负向脉冲的双向不对称波形的抑制效果为最优.结论 低频脉冲刺激脊髓损伤犬阴部神经时,正向脉冲在前的双向不对称脉冲的刺激波形仿真效果最佳,并适用于临床实验,能够有效抑制膀胱过度活动,保护神经避免电化学损伤.     

体表脉冲电刺激大动物的安全性评估

背景：目前电刺激技术已成为研究热点,但其对机体心电活动的影响尚不明确,且既往此方面研究主要针对小型动物。目的：在不影响心电活动的前提下,寻找刺激猪肝区所能使用最大的脉冲电压及频率。方法：取健康雄性荣昌猪3头,将脉冲电刺激仪输出电极固定于猪肝右叶体表投影前后对应部位,设置固定电刺激参数为波宽10 ms、方波,刺激时间为1 h,分别进行5-100 V的电压耐受实验和1-5 Hz的频率耐受实验,观察猪的动态心电图变化、其不适反应和生活行为的改变。结果与结论：电压耐受实验中脉冲电刺激电压高低与心率增量呈正相关;当电压> 35 V时,可发生窦性心律不齐、室性早搏等轻度心律失常,无恶性心律失常、死亡;当电压> 60 V时,可见电刺激诱发形成的qRs波。频率耐受实验中当频率> 2 Hz时可见心律失常发生,无恶性心律失常,脉冲电刺激可诱发形成qRs波。提示选择参数为电压35 V、频率2 Hz的脉冲电刺激猪肝区是安全的,电压大于35 V或频率大于2 Hz的脉冲电刺激猪肝区均可引发心律失常,多为良性心律失常。中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

三叉神经-颈反射检测方法的建立及临床意义

目的：建立三叉神经-颈反射的肌电检测方法，探讨其临床应用价值。方法：70例志愿者取卧位，稍抬高头部使胸锁乳突肌轻度收缩，于眶下孔附近刺激，胸锁乳突肌记录。结果：刺激正常受试者一侧的眶下神经，均可记录到双侧胸锁乳突肌反射的正-负波。结论：三叉神经-颈反射测定技术可靠，在下位脑干损伤的定位诊断中有一定帮助。     

交感中枢不同活动水平下躯体-交感反射的效应

一般认为,刺激躯体神经对心血管活动和交感神经发放的反射效应是和刺激参数有关。本室前阶段提示,刺激躯体神经引起的心血管活动及肾交感神经发放的反射效应还与实验动物的状态以及交感中枢活动水平有关。本工作的目的是进一步观察在交感中枢不同活动水平下弱刺激腓深神经15分钟,对肾交感发放及血压的影响,并对结果作初步     

快速循环伏安法(FCV)在体测定大鼠多巴胺释放

正常雌、雄性大鼠各１５ 只,采用快速循环伏安法分别测定在不同电刺激条件下、刺激大鼠内侧前脑束引起尾状核 壳核复合体多巴胺的释放量。结果：电刺激大鼠内侧前脑束引起的尾状核 壳核复合体多巴胺的释放无明显的性别差异而尾状核 壳核复合体多巴胺释放量与刺激内侧前脑束的电流强度、脉冲数与脉冲频率明显相关。结果提示：研究电刺激大鼠内侧前脑束引起尾状核 壳核复合体多巴胺释放可不考虑性别差异,最适电刺激参数为： 电流强度＝ ８００ μＡ,刺激脉冲数＝ ４０,刺激脉冲频率＝６０ Ｈｚ     

动作电位○期同步触发测定有效不应期

在整体动物心脏上测定有效不应期,因心脏处于自发窦性节律下活动,不宜采用双脉冲直接刺激心肌进行测定,这种方法不能反应在自然搏动下有效不应期的变化。为此,我们设计了以心肌细胞动作电位○期同步触发脉冲去测定有效不应期的方法。     

双向脉冲可实现的神经纤维选择性兴奋

背景：研究证明利用电刺激外周神经纤维可恢复一些因失去中枢神经控制的肌肉的功能。 目的：验证双电极1 mm较近距离下双向方波脉冲实现神经选择性兴奋的正确性,并基于此实现神经的选择性兴奋。 方法：成年Wistar大鼠8只,麻醉后暴露大鼠坐骨神经,将电极小心放于坐骨神经干,建立神经选择性刺激模型。实验用电极为自制Cuff双极性电极,刺激器采用的是Grass S88刺激器和AWG2005任意波形信号发生器。采取双电极双向刺激方式,两个电极之间距离为1 mm,刺激波形选用脉宽为0.2 ms的对称双向脉冲,其输出脉冲的幅度、脉宽和延时均可调。调节刺激强度,研究双电极双向刺激下神经兴奋性的规律,以此实现神经的选择性兴奋,并利用“碰撞法”原理验证利用双电极双向刺激方法实现神经选择性兴奋的可行性。 结果与结论：实验过程中神经动作电位的变化将经P511放大器放大后接入示波器显示,双电极刺激波形为脉宽为0.2 ms的对称双向脉冲。随着刺激幅度的增大,实现神经的选择性兴奋。说明用距离很近(1 mm)的双电极双向对称脉冲的方法实现了神经的选择性兴奋,并利用“碰撞法”原理证实了此种方法的有效性和可行性。     

A comparison of the horizontal and vertical optokinetic reflexes of the rabbit

Summary The horizontal and vertical monocular optokinetic reflexes of the rabbit were measured under closed-loop and open-loop conditions. A random noise, optokinetic stimulus subtending 70×70 deg was presented to the left eye of rabbits placed in front of a rear projection tangent screen. The position of the right eye (nonstimulated) was measured using an infrared light projection technique. During open-loop optokinetic stimulation the eye position signal was fed back to sum with a time-integrated velocity command signal driving the optokinetic stimulus. The dynamics of eye movements evoked by horizontal and vertical optokinetic stimulation were different. Horizontally evoked eye movements never exceeded a deviation of 15 deg before being interrupted by resetting saccades, which returned the eye past the primary position. By contrast, vertical eye deviations greater than 20 deg were often maintained for intervals exceeding 10 s without resetting. The closed-loop gain of optokinetically evoked horizontal eye movements was higher for monocular posterior-anterior optokinetic stimulation than for anterior-posterior stimulation. The vertical optokinetic gain for up-down stimulation was slightly greater than the gain for down-up stimulation. The vertical up-down, open-loop optokinetic gain was greater than the down-up gain over a range of retinal slip velocities of 0.5–5.0 deg/s. Measurement of the horizontal vestibulo-ocular reflex during simultaneous horizontal optokinetic stimulation demonstrated that visual and vestibular information combine linearly to produce reflex eye movements. These data suggest that the higher gain of the horizontal optokinetic reflex may compensate in part for the reduced gain of the horizontal vestibulo-ocular reflex at lower angular accelerations of the head. An equivalent vertical optokinetic gain would be obviated by the contribution of the utricular otoliths to the vertical vestibulo-ocular reflex at low frequencies of head movement.This research was supported by the National Institutes of Health Grant EY00848 and the Oregon Lions Sight and Hearing Foundation     

Eye movements induced by pontine stimulation: interaction with visually triggered saccades

1. Rhesus monkeys were trained to look to brief visual targets presented in an otherwise darkened room. On some trials, after the visual target was extinguished but before a saccade to it could be initiated, the eyes were driven to another orbital position by microstimulation of the paramedian pontine reticular formation. If, as current models of the saccadic system suggest, a copy of the motor command is used as a feedback signal of eye position, failure to compensate for stimulation-induced movements would indicate that stimulation occurred at a site beyond the point from which the eye position signal was derived. 2. Animals compensated for perturbations of eye position induced by stimulation of most pontine sites by making saccades that directed gaze to the position of the visual target. With stimulation at other pontine sites, compensatory saccades did not occur. 3. Pontine stimulation sometimes triggered, prematurely, impending visually directed saccades. The direction and amplitude of the premature movement depended upon the location of the briefly presented visual target. The amplitude of the premature movement was also a function of the interval between the stimulation train and the impending saccade. These data suggest that input signals for the horizontal and vertical pulse/step generators develop gradually during the presaccadic interval. Saccade trigger signals need to be delayed until the formation of these signals is completed. 4. The implications of these findings for models of the saccadic system are discussed. Robinson's local feedback model of the saccadic system can explain compensation for pontine stimulation-induced changes in eye position but cannot easily account for the failure to compensate for perturbations in eye position produced by stimulation at other sites. Modified versions of Robinson's model, which assume that the input signal to the pulse/step generator is the desired displacement of the eye, can account for both compensation and the failure to compensate since two separate neural integrators are employed. However, these models ignore kinematic arguments that commands to the extraocular muscles must specify the absolute position of the eye in the orbit rather than a relative movement from a previous position.     

药源性眼损伤快速评价的斑马鱼模型

目的 苯扎溴铵和羟苯乙酯是广泛应用于眼用制剂的防腐剂,其在眼表的积累是引起眼用制剂药物毒性的重要因素.目前还没有一种简单、快速的方法来检测防腐剂的体内毒性.本研究以苯扎溴铵和羟苯乙酯为探针药物建立一种快速筛选和评价化合物眼毒性的斑马鱼模型和方法.方法 体式显微镜下活体观察斑马鱼幼鱼给药后眼部形态的变化;采用斑马鱼行为学...     

Visual field analyser: Assessment of delay and temporal resolution of vision

The delay campimeter provides a simple and inexpensive means of detecting and measuring abnormally slowed transmission of visual signals from the eye to the brain. Such measurements can assist in the diagnosis of multiple sclerosis. This test can be carried out in 10 min. In an alternative mode of use, a double-flash method is used to assess the extent to which visual signals leaving the eye are sharply defined along the time axis. Additionally, visual sensitivity to flicker can be measured by sinewave-modulating light intensity. Visual stimulation is by switching on, switching off, pulsing or modulating light-emitting diodes, whose relative timing is controlled electronically.     

邻域比较数字滤波——一种对脑电信号进行滤波的有效方法

目的：探讨对脑电时间序列进行邻域比较的数字滤波方法的实用价值。方法：对10例实测脑电信号用邻域比较数字滤波的方法和中值滤波的方法进行处理,观察比较两种方法滤波效果。结果：邻域比较滤波法对叠加有单个噪声脉冲及连续噪声脉冲的脑电信号有很好的去噪效果,对尖波和棘波几乎没有影响,EEG信号无失真。中值滤波法对叠加单个噪声脉冲的脑电信号有效,而对叠加有连续噪声脉冲的脑电信号则失效,并使EEG中尖波,棘波及高频信号失真。结论：在脑电信号处理中,邻域比较数字滤波方法在消除干扰脉冲,保持脑电信号不失真两方面均优于中值滤波法,是一种有实用价值的滤波方法,。     

MR-Eyetracker: a new method for eye movement recording in functional magnetic resonance imaging

 We present a method for recording saccadic and pursuit eye movements in the magnetic resonance tomograph designed for visual functional magnetic resonance imaging (fMRI) experiments. To reliably classify brain areas as pursuit or saccade related it is important to carefully measure the actual eye movements. For this purpose, infrared light, created outside the scanner by light-emitting diodes (LEDs), is guided via optic fibers into the head coil and onto the eye of the subject. Two additional fiber optical cables pick up the light reflected by the iris. The illuminating and detecting cables are mounted in a plastic eyepiece that is manually lowered to the level of the eye. By means of differential amplification, we obtain a signal that covaries with the horizontal position of the eye. Calibration of eye position within the scanner yields an estimate of eye position with a resolution of 0.2° at a sampling rate of 1000 Hz. Experiments are presented that employ echoplanar imaging with 12 image planes through visual, parietal and frontal cortex while subjects performed saccadic and pursuit eye movements. The distribution of BOLD (blood oxygen level dependent) responses is shown to depend on the type of eye movement performed. Our method yields high temporal and spatial resolution of the horizontal component of eye movements during fMRI scanning. Since the signal is purely optical, there is no interaction between the eye movement signals and the echoplanar images. This reasonably priced eye tracker can be used to control eye position and monitor eye movements during fMRI. Received: 7 September 1998 / Accepted: 19 February 1999     

Electrical stimulation of retinal neurons in epiretinal and subretinal configuration using a multicapacitor array

Electrical stimulation of retinal neurons offers the possibility of partial restoration of visual function. Challenges in neuroprosthetic applications are the long-term stability of the metal-based devices and the physiological activation of retinal circuitry. In this study, we demonstrate electrical stimulation of different classes of retinal neurons with a multicapacitor array. The array--insulated by an inert oxide--allows for safe stimulation with monophasic anodal or cathodal current pulses of low amplitude. Ex vivo rabbit retinas were interfaced in either epiretinal or subretinal configuration to the multicapacitor array. The evoked activity was recorded from ganglion cells that respond to light increments by an extracellular tungsten electrode. First, a monophasic epiretinal cathodal or a subretinal anodal current pulse evokes a complex burst of action potentials in ganglion cells. The first action potential occurs within 1 ms and is attributed to direct stimulation. Within the next milliseconds additional spikes are evoked through bipolar cell or photoreceptor depolarization, as confirmed by pharmacological blockers. Second, monophasic epiretinal anodal or subretinal cathodal currents elicit spikes in ganglion cells by hyperpolarization of photoreceptor terminals. These stimuli mimic the photoreceptor response to light increments. Third, the stimulation symmetry between current polarities (anodal/cathodal) and retina-array configuration (epi/sub) is confirmed in an experiment in which stimuli presented at different positions reveal the center-surround organization of the ganglion cell. A simple biophysical model that relies on voltage changes of cell terminals in the transretinal electric field above the stimulation capacitor explains our results. This study provides a comprehensive guide for efficient stimulation of different retinal neuronal classes with low-amplitude capacitive currents.     

A method for reducing motion induced errors in T2-weighted magnetic resonance imaging

It is known that motion of an object imaged by magnetic resonance imaging leads to errors and artifacts in the image. This effect is especially important when a pulse sequence with long echo time (TE) and long TR is used to provide T2-weighted images. We have modified the usual spin warp imaging pulse sequence in a way which greatly reduces the severity of such errors. The method was tested on both a moving phantom and a living rabbit. The pulsing of the scanner was gated in synchrony to the motion of the phantom; two pulses per mechanical cycle were used to create a special situation which served to verify the validity of a theoretical analysis of the loss of signal with echo time. Under such conditions it was shown that the conventional method led to a progressive loss of signal with increasing TE while the new method gave a pure exponential decay of signal in accordance with the known T2 of the sample. When either the phantom or the animal was scanned without gating, the new pulse sequence showed far less artifacts attributable to motion. The potential application of the technique to improved quantitative imaging of the abdomen in clinical situations is discussed.     

Interaction between the horizontal vestibulo-ocular reflex and optokinetic response in rabbits

Summary Dynamic characteristics of the horizontal vestibulo-ocular reflex (HVOR), the optokinetic response (OKR), and their interactions were investigated in alert albino rabbits. For stimulation of the horizontal semicircular canals, the whole rabbit was rotated sinusoidally on a motor-driven turntable at peak-to-peak amplitudes of 5 ° to 30 ° over a frequency range of 1/30 to 1/2 Hz. Optokinetic stimulation was provided by a narrow vertical slit light source presented in front of the eye to be tested. The evoked horizontal eye movements were observed and measured by means of a closed circuit television system adapted to provide an analog signal proportional to the eye movement. The net HVOR was obtained by rotation of the turntable in darkness and the net OKR by rotation of the light source. Combining rotation of the turntable with a stationary light source immediately increased the gain and reduced the phase shift of the HVOR. The light source moving in phase with the turntable, but at twice the angular amplitude, reduced the gain and advanced the phase of the HVOR. Eye movement curves of the HVOR modified by a fixed or moving slit light could be reconstructed approximately by a linear combination of the net HVOR and OKR.The work was supported by a grant from the Japanese Ministry of Education, Science and Culture (987008)On leave from C.N.R.S., France (from Nov. 1974 to Feb. 1975) and supported by a Franco-Japanese Cultural Relations Program FellowshipOn leave from C.N.R.S., France (from Nov. 1974 to Feb. 1975) and supported by a visiting professorship from Japan. Society for the Promotion of ScienceOn leave from Nencki Institute of Experimental Biology, Warsaw (from Jan. 1977 to Jan. 1978) and supported by a Polish-Japanese Cultural Relations Program Fellowship     

Optokinetic nystagmus in the rabbit and its modulation by bilateral microinjection of carbachol in the cerebellar flocculus

Summary 1. In the alert, pigmented rabbit, eye movements were recorded during optokinetic nystagmus (OKN) and during optokinetic afternystagmus (OKAN). These responses were elicited by steps in surround-velocity ranging from 5–110°/s during binocular as well as monocular viewing. 2. In the baseline condition, OKN showed an approximately linear build-up of eye velocity to a steady-state, followed by a linear decay of eye velocity during OKAN after the lights were turned off. Build-up during binocular viewing was characterized by a constant, maximum eye-acceleration (about 1°/s²) for stimulus velocities up to 60°/s. OKAN, instead, was characterized by a fixed duration (about 10 s) for stimulus velocities up to 20°/s. Steady-state eye velocity saturated at about 50°/s. 3. Monocular stimulation in the preferred (nasal) direction elicited a build-up that was on average twice as slow as during binocular stimulation. Steady-state velocity during monocular stimulation saturated at about 20°/s. OKAN was of equal duration as during binocular stimulation. In the non-preferred direction, a very irregular nystagmus was elicited without velocity build-up. The stronger response to binocular stimulation, compared to the responses under monocular viewing condition in either nasal and temporal direction suggests potentiation of the signals of either eye during binocular viewing. 4. OKN and OKAN were re-assessed after intra-floccular microinjection of the nonselective cholinergic agonist carbachol. In the binocular viewing condition, eye-acceleration during build-up was strongly enhanced from 1°/s² before to 2.5°/s² after injection. The saturation level of steady-state eye velocity was also increased, from 50°/s before to more than 60°/s after carbachol. The duration of OKAN, however, was shortened from 10 s before to 6 s after injection. The response to monocular stimulation in the preferred direction revealed similar changes. 5. The flocculus appears to be involved in the control of the dynamics of OKN in the rabbit. Cholinergic mechanisms affect the floccular control of the rate at which slow-phase velocity can be built up and the rate of decay of eye velocity during OKAN. Cholinergic stimulation of the flocculus enhances the dynamics of OKN, while velocity storage is shortened.