瞳孔控制系统采样特性的中枢机制

本文以双脉冲光分眼刺激（ｄｉｃｈｏｐｔｉｃ ｓｔｉｍｕｌａｔｉｎｇ,双脉冲的第一脉冲光刺激一侧眼,第二脉冲光刺激另一侧眼）进行瞳孔采样特性研究。实验结果表明：当双脉冲之间的时间间隔较长时,瞳孔产生两次收缩反应;当时间间隔小于约０．６ｓ时,瞳孔只对第一个脉冲光刺激产生瞬态收缩,对第二个脉冲光刺激不产生反应。这不仅证实了单眼实验研究的结论：瞳孔系统不是在时间上连续进行控制,而是离散的采样控制,它对光刺     

视觉图形诱发的瞳孔反应

以图形变化刺激进行瞳孔反应研究,实验表明：（１）空间平均亮度守恒的光栅或棋盘格图形翻转能激发起瞳孔反应,为瞬态收缩波形,与ｐｕｐｉｌｌａｒｙ ｅｓｃａｐｅ相似;（２）光栅或棋盘格的空间频率的变化也能引起瞳孔反应,且反应幅度随空间频率差别增大而变大;（３）从均匀亮背景变化到棋盘格图形或者从棋盘格图形变化到黑暗背景,虽然不存在任何局部亮度增强,皆能引起瞳孔反应。实验结果明确证明了人的瞳孔反应系统除接收     

用于研究快速扫视对瞳孔光反射调制作用的新方法

瞳孔对光反射系统和快速扫视系统在解剖学和功能上都有着紧密的联系,但是快速扫视系统对瞳孔的光反射系统是否有调制作用尚无报道。研究这两个系统间的调制作用,必须了解光刺激不均匀和近反应对瞳孔直径变化是否有影响。该研究以人为被试,设计了一种全新的实验方法,研究光刺激不均匀和近反应对瞳孔直径变化的影响。实验方法：将被试的一只眼用密闭的眼罩罩住给予脉冲光刺激,刺激由位于眼罩内全视野范围水平排列的一排发光二极管(light emitting diodes,LEDs)给出,被试的另一只眼用来记录眼动和瞳孔直径的变化,研究水平方向的快速扫视对瞳孔对光反射时瞳孔直径变化的影响。实验结果：比较被试注视视野内不同位置的瞳孔对光反射相对收缩率无显著差异（P=0.148, 非配对样本t检验）。结论：本方法消除了光刺激不均匀和近反应对瞳孔直径变化的影响,可用于研究快速扫视系统对瞳孔光反射系统间的调制作用。     

瞳孔光反应系统的空间分布式神经网络模型

为模拟刺激光空间分布变化引起瞳孔反应的实验现象,本文建立了空间分布式神经网络瞳孔模型。它是在瞳孔双通道模型基础上,借鉴Ｃａｎｎｏｎ－Ｒｏｂｉｎｓｏｎ的Ｏｃｕｌｏｍｏｔｏｒ模型的双层网络结构和视网膜的镶嵌式特点,经空间延括而成。空间各部位信号经第一层神经元处理得到对应各部位的线性ＤＣ和非线性ＡＣ输出,在第二层神经元进行空间综合,再经第三层神经元复合去控制效应器官虹膜肌的反应。该分布式部位机制模型能解释多种瞳孔实验现象。     

猫外膝体神经元对正弦调制光刺激反应的线性和非线性特性

用不同频率正弦波调制发光二极管亮度,刺激猫外膝体细胞的感受野中心。用Apple-Ⅱplus 计算机将细胞放电频率的瞬时变化作成反应直方图(PSTH)。通过傅里叶变换,计算平均放电率、基波幅度和高次谐波幅度的变化,定量地研究了细胞反应的线性和非线性性质。 1.在恒定的平均亮度下,持续细胞的反应具有较好的线性特征,表现在PSTH可以重现正弦光刺激的频率和波形;与此相反,瞬变细胞的反应显示明显的非线性性质,PSTH出现半波整流波形,反应上升相交陡而下降相较平缓。 2.两类细胞对正弦刺激的反应具有不同的谐波成分:典型持续细胞的反应中主要包含基波成分,高次谐波的幅度接近噪声水平;但是,瞬变细胞的谐波可以延续到8次之多,二次和三次谐波的幅度可高达基波幅度的50％。 3.逐渐增加调制光刺激的平均亮度,持续细胞反应中二次谐波幅度始终保持在很低的水平上,而瞬变细胞的谐波幅度则随着增大。 4.增加光刺激的调制深度,持续细胞的反应特点是:(1)平均放电率保持不变或略有增加,(2)二次谐波增长很慢,(3)基频相位基本保持不变。与此相反,瞬变细胞的平均放电率和二次谐波幅度都随调制深度增加而明显地增大,并且基波相位也可见到较明显的前移。 以上结果表明,持续细胞与瞬变细胞在时间域方面也具有线性和非线性的差别。     

变间隔的脉冲改变高频刺激对于脑神经元的作用

通常采用恒定电脉冲间隔的高频刺激(high-frequency stimulation,HFS),进行深部脑刺激治疗帕金森氏症等运动障碍疾病.为了开发适用于不同脑疾病治疗的新刺激模式,近年来脉冲间隔(inter-pulse-interval,IPI)变化的变频刺激模式受到关注.已有研究表明,即使具有相同的平均电脉冲频率,变频刺激与恒频刺激的治疗效果也不同.我们推测,变频刺激的短小IPI变化就足以改变HFS对于神经元的作用.为了验证此推测,本文在大鼠海马CA1区锥体神经元的输入轴突纤维上交替施加恒频刺激(100或133 Hz,即IPI=10 ms或7.5 ms)和随机变频刺激(100～200 Hz,即IPI=5～10 ms,平均频率为133 Hz),记录并分析刺激下游神经元群体的诱发电位,用于定量评价神经元对于恒频和变频刺激的响应.实验结果表明,持续的恒频刺激使得神经元的响应从最初的同步发放形成的群峰电位(population spike,PS)转变为非同步的动作电位发放(即单元锋电位).但是,当刺激切换为变频模式时,却又可以诱发神经元群体同步产生动作电位,重新形成PS波.并且,变频刺激诱发的PS幅值和神经元发放的同步程度可达基线的单脉冲刺激诱发波的水平.但是,PS的发生率只有脉冲刺激频率的7%左右,表明在持续的变频刺激时,多个脉冲累积的作用才能诱发这种同步的神经元发放.而且PS的出现与前导IPI的长度之间存在一定关系.神经元的轴突和突触等结构对于高频刺激的非线性响应可能是变频刺激诱发同步活动的原因.这些结果表明,变频刺激序列中短小的间隔变化可以产生与恒定间隔不同的调控作用.本文的结果对于揭示脑刺激的作用机制,促进新型刺激模式的开发及其在不同类型脑疾病治疗中的应用具有重要意义.     

藜芦碱致使大鼠背根神经节A类神经元产生触发性振荡

在大鼠L5背根节浸浴钠通道失活门阻断剂藜芦碱（veratridine),记录该背根节神经元A类单纤维传入放电。发现：浸浴藜芦碱（1．8－3μmol/L）10min后,触压皮肤感受野或刺激坐骨神经引起部分静息纤维产生高频放电,其放电峰峰间期（interspike interval,ISI)形成U字形等型式的振荡,称之为触发性振荡。刺激脉冲的间隔越大,触发该振荡所需要的刺激脉冲数也就越多;不同时程和形式的刺激引起触发性振荡的形式无明显差异;触发性振荡的后抑制时期一般为30－90s。另外,实验还观察到该触发性振荡可由同一神经刺激引起的传入冲动触发。上述结果表明,用黎芦碱处理可使初级感觉神经元产生一种触发性振荡,该振荡机制可能与触发病的发作有关。     

大鼠离体视皮层神经元短时程时间整合特性的研究

用双脉冲白质电刺激研究了８７个大鼠视皮层神经元的短时程时间整合特性。第一个脉冲所引起的细胞反应对第二个反应有影响的细胞占被记录细胞总数的５５．２％,其中表现为突触作用增强的占４１．７％,表现为突触作用压抑的占５８．３％。整合作用的强度决定于两个脉冲之间的时间间隔,作用形式主要表现为第二个刺激所引起的反应的幅度和时程的改变。电反应可以ＥＰＳＰ或ＩＰＳＰ为主,或由ＥＰＳＰ和ＩＰＳＰ混合组成。部分细胞的反应包含快慢两个成份,时间整合作用对不同反应成份的影响程度有明显的不同。在锥体神经元中,增强型和压抑型的比例大致相等,而非锥体神经元只显示压抑型作用。位于皮层深层的神经元有时间整合作用的比率（３７．５％）比位于浅层的神经元（６０．５％）要低得多。     

人左右颈动脉窦反射有功能不对称性

在30名24～38岁的健康受试者身上研究了对左右侧颈动脉压力感受器活动(CBA)和不活动(CBI)所引起的反射性心脏反应。实验是在受试者安静卧位下进行的。CBA是用两个分开的小颈室(neck chamber)对左右侧窦区施加10s负压(-20～-60mmHg)引起的。CBI是通过给颈部左右侧施加10s正压(20～60mmHg)产生的。当CBA和CBI时,继续保持平静呼吸。从心电图测量R—R间期。对每一个单独刺激,先求出颈部抽气(压力)前10s内R—R间期的平均值作为基线测量。把R—R间期的毫秒变化的最高值表示反应。用多普勒扫描器在胸骨上的切口测量血流速度,以血流加速程度作为左心室收缩力的指标。结果R—     

大鼠海马神经元对于高频脉冲刺激的暂态响应

闭环刺激是深部脑刺激(deep brain stimulation,DBS)的重要发展方向之一,有望用于治疗多种脑神经系统疾病.与常规开环的长时间持续刺激不同,闭环刺激通常采用短促的高频脉冲序列.而神经元对于高频刺激的响应存在暂态过程,在初期的短时间内会发生很大变化,从而影响闭环刺激的作用.为了研究这种暂态过程,在大鼠海马CA1区传出轴突纤维(alveus)上施加不同频率的恒频以及随机变频的逆向高频刺激(antidromic high-frequency stimulation,A-HFS),并以逆向诱发的群峰电位(antidromically-evoked population spike,APS)的幅值作为指标来考察神经元群体的响应.研究结果表明,100、133和200 Hz的恒频A-HFS初期,APS迅速衰减,脉冲频率越高,APS衰减越快.平均不到1 s时间内APS的幅值就会下降一半以上,100 Hz时的平均半衰期为～0.96 s,频率增加1倍至200 Hz时,平均半衰期缩短至～0.21 s.使用100～200 Hz范围内实时微调脉冲间隔的随机变频刺激,则可以显著延缓神经元响应的衰减速度,延长刺激作用的维持时间.这些结果可以为短促闭环刺激等DBS新模式的开发提供依据.     

Binocular alternating pulse stimuli: Experimental and modeling studies of the pupil reflex to light

In our experiment, alternating pulse stimuli of both low and high intensity are used to study the pupil reflex to light. When applied monocularly, high intensity stimulation normally results in a sustained contraction; when alternated between the two eyes, it is found to produce small transient responses similar to those obtained with low intensity monocular stimulation. In order to study the mechanisms regulating these binocular responses, a model of the pupillary light reflex is constructed. It includes parallel AC and DC pathways for processing the light stimulus to produce motor signals to the iris muscles, nonlinear parameter control of pathway gains dependent upon internal operating level, binocular summation of DC pathway signals to produce that operating level, equal motor responses of both pupils, and iris neuromuscular delays and lags. The model is found to simulate the experimental data. It shows the binocular transient responses to be due to the canceling by summation of the symmetric DC pathway responses to alternating stimuli, thus allowing the AC pathway signals to become manifest. Therefore the dilatory portion of the transient responses is shown to be due to the lead-lag operator in the AC pathway and not to the off-dilatation elicited by removal of the light stimulus from the eye. Finally the results of our study are used to discuss the Marcus Gunn pupillary sign, a clinical test utilizing this binocular alternating pulse stimulation for detecting unilateral afferent defects.     

Neural network mosaic model for pupillary responses to spatial stimuli

A neural network mosaic model was developed to investigate the spatial-temporal properties of the human pupillary control system. It was based on the double-layer neural network model developed by Cannon and Robinson and the pupillary dual-path model developed by Sun and Stark. The neural network portion of the model received its input from a sensor array and consisted of a retina-like two-dimensional neuronal layer. The dual-path portion of the model was composed of interconnections of the neurons that formed a mosaic of AC transient and DC sustained paths. The spatial aggregates of the AC and DC signals were input to the AC and DC summing neurons, respectively. Finally, the weighted sum of the aggregate AC and DC signals provided the output for driving the pupillary response. An important property of the model was that it could adaptively learn from training samples by adjustment of the weights. The neural network mosaic model showed excellent performance in simulating both the traditional pupillary phenomena and the new spatial stimulation findings such as responses to change in stimulus pattern and shift of light spot. Moreover, the model could also be used for the diagnosis of clinical deficits and image processing in machine vision. Received: 12 December 1997 / Accepted in revised form: 22 April 1998     

瞳孔控制系统非线性的频率特性与固有频率

本文用实验方法从时域和频域上揭示了瞳孔对光反应的非线性特性.在亮度以正弦变化的光刺激下,瞳孔反应波形呈同步倍频现象;描述函数的频率-振幅特性曲线呈多峰的锯齿形;具有1.2Hz左右的系统固有频率和极限环现象.     

Level dependent signal flow in the light pupil reflex

Latency of pupillary responses to light stimuli are smaller for larger steps of light, and larger for smaller steps of light (Alpern 1954; Lowenstein et al. 1964; Lee et al. 1969; Terdiman et al. 1969; Cibis et al. 1977; and many others). Miller and Thompson (1978), however, reported negligible change in pupil cycle time (period of high gain instability oscillations) with increased mean brightness. Sandberg and Stark (1968) reportd a negligible reduction in phase lag of pupillary responses to sinusoidal light stimuli as the modulation coefficient (m) increased. To resolve the inconsistency between the well-documented dependence of latency upon brightness, and the apparent absence of level dependence in the phase characteristics (as reflected directly in the responses to sinusoidal stimuli and indirectly in pupil cycle time experiments) we measured: 1. Latency to step stimuli of light, 2. Phase of responses to sinusoidal light stimuli and 3. Period (pupil cycle time) of high gain instability oscillations. The dependence of pupillary latency upon stimulus level (both light and accommodation) and the interaction between accommodation and light responses were investigated. We show that most of the level dependence of light-pupil latency resides in the afferent path. In the companion papers, we demonstrate that: 1. Phase of pupillary response to sinusoidal light stimuli is reduced by increased mean light level, but is independent of pupil size and accommodative stimulus level; and 2. The period of high gain oscillations is shown to decrease with increased mean light level. Taken together, these results imply the existence of a Level Dependent Signal Flow (LDSF) operator that resides in the light-pupil pathway, but not in the accommodation-pupil pathway. We propose a systems model of this operator in which the neural signals controlling pupil size are treated as waves whose phase velocity increases in response to brighter stimuli, and decreases in response to dimmer stimuli. When parameters of the model are adjusted to fit measured pupillary latency over a range of light levels, the model exhibits reduced phase lag in response to increased mean light level in the sinusoidal paradigm, and it exhibits reduced pupil cycle time in the high-gain oscillation paradigm. The model exhibits saturation of the LDSF effect in all paradigms at high light levels, as do experimental results. It simulates directional asymmetry of pupillary response to positive and negative steps of light, with constriction more rapid than dilatation. Finally, it simulates tonic pupillary constriction in response to modulation of a light simulus without changing average light level (Varju 1964; Troelstra 1968). All of these stimulated results are in accord with experimental observation.     

Light-induced changes of sensitivity in Limulus ventral photoreceptors

The responses of Limulus ventral photoreceptors to brief test flashes and to longer adapting lights were measured under voltage clamp conditions. When the cell was dark adapted, there was a range of energy of the test flashes over which the peak amplitude of the responses (light-induced currents) was directly proportional to the flash energy. This was also true when test flashes were superposed on adapting stimuli but the proportionality constant (termed peak currently/photon) was reduced. The peak current/photon was attenuated more by brighter adapting stimuli than by less bright adapting stimuli. The peak current/photon is a measure of the sensitivity of the conductance-increase mechanism underlying the light response of the photo-receptor. The response elicited by an adapting stimulus had a large initial transient which declined to a smaller plateau. The peak current/photon decreased sharply during the declining phase of the transient and was relatively stable during the plateau. This indicates that the onset of light adaptation is delayed with respect to the onset of the response to the adapting stimulus. If the adaptational state just before the onset of each of a series of adapting stimuli was constant, the amplitude of the transient was a nearly linear function of intensity. When the total intensity was rapidly doubled (or halved) during a plateau response, the total current approximately doubled (or halved). We argue that the transition from transient to plateau, light-elicited changes of threshold, and the nonlinear function relating the plateau response to stimulus intensity all reflect changes of the responsiveness of the conductance-increase mechanism.     

The Light Growth Response of Phycomyces

With the help of an automated tracking system we have studied the characteristics of the transient light growth response of Phycomyces. The response shows a sharply defined latency. The Q₁₀ of the reciprocal latency is 2.4. Response patterns at different peaks of the action spectrum are the same. The gradual variation of response magnitude over a wide range of adapted intensifies parallels that of phototropism. The responses to saturating stimuli exhibit a strong oscillation with a constant period of 1.6 min and variable damping. The growth responses to sinusoidally varying light intensities show a system bandwidth of 2.5 x 10^-3 Hz. The linear dependence of phase shift on frequency is largely attributable to the latency observed with pulse stimuli. In the high intensity range a previously suspected increase of the steady-state growth rate with intensity has been confirmed. The light growth responses of mutants selected for diminished phototropism have been investigated. Many of these mutants have sizable but grossly distorted growth responses.     

A linear chromatic mechanism drives the pupillary response.

Previous studies have shown that a chromatic mechanism can drive pupil responses. The aim of this research was to clarify whether a linear or nonlinear chromatic mechanism drives pupillary responses by using test stimuli of various colours that are defined in cone contrast space. The pupil and accommodation responses evoked by these test stimuli were continuously and simultaneously objectively measured by photorefraction. The results with isochromatic and isoluminant stimuli showed that the accommodative level remained approximately constant (< 0.25 D change in mean level) even when the concurrent pupillary response was large (ca. 0.30 mm). The pupillary response to an isoluminant grating was sustained, delayed (by ca. 60 ms) and larger in amplitude than that for a isochromatic uniform stimulus, which supports previous work suggesting that the chromatic mechanism contributes to the pupillary response. In a second experiment, selected chromatic test gratings were used and isoresponse contours in cone contrast space were obtained. The results showed that the isoresponse contour in cone contrast space is well described (r(2) = 0.99) by a straight line with a positive slope. The results indicate that a /L - M/ linear chromatic mechanism, whereby a signal from the long wavelength cone is subtracted from that of the middle wavelength cone and vice versa, drives pupillary responses.     

Stochastic Properties of Discrete Waves of the Limulus Photoreceptor

In the dark-adapted photoreceptor of the horseshoe crab, Limulus, transient discrete depolarizations of the cell membrane, discrete waves, occur in total darkness and their rate of occurrence is increased by illumination. The individual latencies of the discrete waves evoked by a light stimulus often cannot be resolved because the discrete waves overlap in time. The latency of the first discrete wave that follows a stimulus can be determined with reasonable accuracy. We propose a model which allows us to make an estimate of the distribution of the latencies of the individual light-evoked discrete waves, and to predict the latency distribution of the first discrete wave that follows a stimulus of arbitrary intensity-time course from the latency distribution of the first discrete wave that follows a brief flash of light. For low intensity stimuli, the predictions agree well with the observations. We define a response as the occurrence of one or more discrete waves following a stimulus. The distribution of the peak amplitudes of responses suggests that the peak amplitude of individual discrete waves sometimes has a bimodal distribution. The latencies of the two types of discrete waves, however, follow similar distributions. The area under the voltage-time curve of responses that follow equal energy long (1.25 sec) and short (10 msec) light stimuli follows similar distributions, and this suggests that discrete waves summate linearly.