基于有限元法的硬脑膜外视皮层电刺激仿真研究

经硬脑膜对视皮层电刺激是治疗失明的新思路。为从理论上认识其作用机制,首先建立视皮层区域的有限元仿真模型,分析脑组织内电场分布,并用激活函数和组织活化区来表征外加刺激的作用效果;随后逐次改变单相脉冲的幅值、脉宽和频率,通过基波作用下组织活化区的变化来探讨不同刺激参数对结果的影响。仿真结果显示,经硬脑膜可以实现对视皮层的有效刺激,只是所需刺激强度比直接皮层刺激约高30倍;多电极刺激模式下,只要电极间距超过5 mm,电极间的影响可忽略不计;降低幅值、脉宽和频率等参数,可以改善单相方波脉冲的刺激效果,其中幅值的减小对空间分辨率的提高效果最为显著。所得结论对实验具有一定指导意义。     

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.     

视皮层中神经元的同步发放现象黄江涛1

在Hindmarsh-Rose(HR)单神经元模型的基础上,结合视皮层的神经网络模型,研究分析视皮层中各神经元的发放模式.数值仿真显示:视皮层网络结构的各层中,神经元的发放具有同步现象;当双极细胞的外界刺激改变时,神经元出现簇发放和峰发放两类模式;随着外界刺激强度的增强,电位发放的峰峰间距(ISI)显示分岔现象.     

基于COMSOL和NEURON的坐骨神经电刺激模型

为研究周围神经在接受电刺激时的兴奋规律,建立了坐骨神经电刺激的仿真模型。利用有限元仿真软件COMSOL对神经和卡肤电极建模并计算神经周围在外加刺激下的电场分布情况,将此电场分布信息导入到神经建模软件NEURON建立的神经模型中作为细胞外激励源,以分析电刺激下神经的电生理行为。在此模型上分析了刺激电极尺寸和间距、电刺激波形、环境温度和局部温度等参数对坐骨神经纤维兴奋性的影响,为神经功能电刺激的进一步研究及临床应用提供了理论基础。     

视皮层中神经元的同步发放现象

在Hindmarsh—Rose（HR）单神经元模型的基础上，结合视皮层的神经网络模型，研究分析视皮层中各神经元的发放模式。数值仿真显示：视皮层网络结构的各层中，神经元的发放具有同步现象；当双极细胞的外界刺激改变时，神经元出现簇发放和峰发放两类模式；随着外界刺激强度的增强，电位发放的峰峰间距（ISI）显示分岔现象。     

刺入式电极刺激视神经的仿真研究

目的 刺入式电极激活视神经纤维是发展视神经假体的新思路.以MATLAB为平台建立仿真系统来研究其作用机制,并通过改变刺激参数来探讨刺激效果.方法 首先建立视神经的容积导体模型和视神经纤维模型,然后计算在刺入式电极刺激下不同深度纤维的兴奋阈值,并用激活函数和组织激活区来表征外加刺激的作用效果；随后改变纤维的直径、刺激脉冲脉宽来探讨不同参数对刺激效果的影响.结果 兴奋阈值随着电极-纤维距离的增加增大,此时视神经内能同时被激活的纤维数量增多；增大纤维直径,同一深度纤维兴奋阈值会减小,电极-纤维距离越大,阈值减小程度也越大；增加单相矩形波脉宽,兴奋阈值减小,脉宽大于0.5 ms时,同一深度纤维兴奋阈值几乎不再随脉宽增加而变化.结论 刺入式电极可以实现对视神经的有效刺激,不同的刺激参数能产生不同的激活效应.所得结论对实验具有一定的指导意义.     

大鼠前连合核神经元对渗透压和血管紧张素Ⅱ刺激的神经性反应——脑片电生理研究

在大鼠下丘脑离体脑片上,用电生理细胞外记录法研究了前连合核神经元的放电频率及其波形。实验观察到的前连合核自发放电神经元有不规则或规则的连续性放电活动,少数神经元有短阵性放电或不放电。这些神经元中的绝大部分可因脑片浸浴液中给予血管紧张素Ⅱ而被兴奋(放电频率增加),约1/3—1/2神经元对高渗透压刺激呈抑制性反应(放电频率减少),也有少数神经元可因高渗透压刺激而兴奋或无反应。前连合核的这些电生理特性大致与视上核、室旁核相似,也有一些与视上核、室旁核不同之处。对记录后的脑片进行组织化学及免疫组织化学染色的结果表明,记录部位在前连合核内,该部位有许多催产素样免疫阳性社经元。上述研究结果提示:前连合核的大细胞神经分泌神经元在水平衡的调节中起重要作用。     

外部电场作用下的视神经纤维兴奋性的仿真研究

基于刺入式电极的视神经视觉假体,为盲人的视觉修复提供了新的可能性。为了对该视神经假体的电刺激策略和微电极设计提供理论支持,基于真实的电极结构,在COMSOL软件中建立刺入式微电极的外部电场仿真模型,并将其与利用NEURNO软件实现的神经纤维双层电缆模型结合,系统地研究电极与视神经纤维的相对位置、电刺激脉冲宽度以及电极几何结构的改变对视神经纤维兴奋阈值的影响。不同电极位置、刺激脉宽刺激下阈值变化规律的仿真结果,与以往报道的动物实验和仿真实验结果相符,证明了所建模型的有效性。 根据仿真结果,对刺入式视神经假体中刺激脉宽的选择和电极几何结构的设计,建议如下：窄脉宽刺激有利于降低能量消耗;电极锥度的设计要在满足电极力学特性及易于植入视神经的基础上,尽可能地减小,以降低纤维兴奋的阈值;电极的暴露面积越小,纤维兴奋所需的电流阈值越低,但电荷密度阈值越高;较低的电流阈值有利于减少能量消耗,但过高的电荷密度阈值却容易造成组织损伤,因此电极暴露面积的设计需要在耗能与安全性之间进行综合考虑。电极绝缘层厚度的改变对视神经纤维的兴奋阈值没有明显的影响,但从电极插入的难易考虑,应尽可能减小绝缘层厚度。以上结果对人体其他部位神经纤维的电刺激同样具有参考价值     

胃电刺激对大鼠VMH胃扩张敏感神经元电活动及脑内催产素表达的影响

目的： 给予胃窦部以2组不同参数的电刺激，观察大鼠下丘脑腹内侧核（VMH）胃扩张（GD）敏感性神经元放电频率的变化及脑内有促进摄食作用的神经肽-催产素(OT) 表达的变化，为胃电刺激（GES）治疗肥胖的中枢作用机制及临床上治疗肥胖参数的选择提供理论依据。方法: ① 电生理实验：采用细胞外记录神经元单位放电方法，记录下丘脑腹内侧核神经元自发放电活动，根据神经元对胃扩张刺激反应的不同，分为胃扩张兴奋性神经元（GD-E）和胃扩张抑制性神经元（GD-I）， 并观察不同参数电刺激胃窦部，VMH内GD-E和GD-I放电频率的变化。②免疫组化实验：采用免疫荧光组织化学染色方法观察胃电刺激 2 h 对大鼠脑内OT阳性神经元表达的影响。结果: ① 电生理结果：GES1和GES2分别使60.4%和75.0%的GD敏感性神经元兴奋（P>0.05）。GES2和GES1分别可使GD-E神经元的放电频率平均增加343.59%±89.19%和97.44±33.67% (P<0.05)，GD-I神经元的放电频率平均增加366.30%±87.20%和112.00%±14.67% (P<0.05)。②免疫组化结果：GES1刺激胃窦部 2 h，室旁核（PVN）和视上核（SON）OT 免疫阳性神经元明显增加（P<0.05）。结论: GES可通过兴奋“饱中枢”-VMH内胃扩张敏感性神经元和增加脑内OT的表达来抑制摄食，且GES的作用效应与其强度有关。     

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。     

Effect of prolonged cortical stimulation differs with size of infarct after sensorimotor cortical lesions in rats

Motor deficit improvement is limited in rats with a large sensorimotor cortex infarct, even with cortical stimulation during rehabilitation. However, we find prolonged stimulation that differs with the size of cortical lesion to be effective. Two weeks of prolonged epidural electrical stimulation and rehabilitative training were delivered to rats whose cortex had been subjected to photothrombotic infarct after training in a single-pellet reaching task. Continuous stimulation greatly improved recovery in animals with large infarcts (6 mm diameter), while intermittent stimulation was more effective in animals with small (4 mm) lesions. Thus, prolonged cortical stimulation is a strategy to enhance motor recovery in photothrombotic infarct model rats. However, pattern and duration of stimulation requires modification depending on the extent of infarct.     

Modelling motor cortex stimulation for chronic pain control: Electrical potential field, activating functions and responses of simple nerve fibre models

This computer modelling study on motor cortex stimulation (MCS) introduced a motor cortex model, developed to calculate the imposed electrical potential field characteristics and the initial response of simple fibre models to stimulation of the precentral gyrus by an epidural electrode, as applied in the treatment of chronic, intractable pain. The model consisted of two parts: a three-dimensional volume conductor based on tissue conductivities and human anatomical data, in which the stimulationinnduced potential field was computed, and myelinated nerve fibre models allowing the calculation of their response to this field. A simple afferent fibre branch and three simple efferent fibres leaving the cortex at different positions in the precentral gyrus were implemented. It was shown that the thickness of the cerebrospinal fluid (CSF) layer between the dura mater and the cortex below the stimulating electrode substantially affected the distribution of the electrical potential field in the precentral gyrus and thus the threshold stimulus for motor responses and the therapeutic stimulation amplitude. When the CSF thickness was increased from 0 to 2.5 mm, the load impedance decreased by 28%, and the stimulation amplitude increased by 6.6 V for each millimetre of CSF. Owing to the large anode-cathode distance (10 mm centre-to-centre) in MCS, the cathodal fields in mono- and bipolar stimulation were almost identical. Calculation of activating functions and fibre responses showed that only nerve fibres with a directional component parallel to the electrode surface were excitable by a cathode, whereas fibres perpendicular to the electrode surface were excitable under an anode.     

脊髓硬膜外电刺激的数学模型

为研究直接脊髓神经电刺激下场的分布规律,构建尽可能模拟脊髓在电刺激作用下的数学模型,本研究将硬膜外电刺激下的脊柱理想化为圆柱,理论推导了点电流源刺激下脊髓及被膜组织中场的分布模型,并利用Matlab对模型进行模拟,分析了刺激电极下电位场和电流密度场的分布规律。结果表明直接脊髓电刺激对脊髓神经通路的作用是局部的而非整体刺激,刺激的范围受电极摆放位置的影响,这将对直接脊髓刺激在临床中的正确使用起到理论指导意义。     

Plasticity in cat visual cortex restored by electrical stimulation of the locus coeruleus

It has been proposed that the presence of noradrenaline (NA)-containing terminals and NA-related receptors within the visual cortex is necessary to maintain the high level of neuronal plasticity in the immature visual cortex of kittens. In the present study we wanted to show whether electrical stimulation of the locus coeruleus (LC), which contains the somata of these cortical NA fibers, can restore neuronal plasticity to the normally aplastic visual cortex of juvenile and adult cats. We consistently found a significant loss of binocular cells in the visual cortex of mature animals which had monocular vision for only 12 h dispersed over 6 days (2 h a day, otherwise kept in the dark) in combination with concurrent LC stimulation. This result was interpreted as indicating that endogenous NA released from NA terminals restored susceptibility to monocular vision in the mature visual cortex. We next examined how long the restored plasticity lasts in the same animals after the LC stimulation was ended. The animals revived from the first recording session were either returned to the same daily schedule of brief monocular exposure (light/dark = 2/22 h) as before, or subjected to the usual monocular lid suture and kept in a cat colony environment (light/dark = 16/8 h). The LC electrodes had been removed and no more electrical stimulation was delivered at this stage. In the animals subjected to reiteration of brief monocular exposure, the state of reduced binocularity gradually returned to normal over a period of 2-3 weeks after stopping LC stimulation. We calculated that the revived plasticity disappeared at an average rate of a 22% loss every 7 days. This result sharply contrasted with the result obtained in the animals subjected to usual monocular lid suture. In this test the state of reduced binocularity continued for at least the next 3 weeks, suggesting that the restored plasticity was sustained throughout a period of 3 weeks (longest term tested). The different results obtained in the two paradigms may be explained by the different strength of binocular imbalance in the two tests imposed on the visual cortex in which neuronal plasticity was restored partially.     

Phosphene induction and the generation of saccadic eye movements by striate cortex

The purpose of this review is to critically examine phosphene induction and saccadic eye movement generation by electrical microstimulation of striate cortex (area V1) in humans and monkeys. The following issues are addressed: 1) Properties of electrical stimulation as they pertain to the activation of V1 elements; 2) the induction of phosphenes in sighted and blind human subjects elicited by electrical stimulation using various stimulation parameters and electrode types; 3) the induction of phosphenes with electrical microstimulation of V1 in monkeys; 4) the generation of saccadic eye movements with electrical microstimulation of V1 in monkeys; and 5) the tasks involved for the development of a cortical visual prosthesis for the blind. In this review it is concluded that electrical microstimulation of area V1 in trained monkeys can be used to accelerate the development of an effective prosthetic device for the blind.     

Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex.

1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans-synaptically activated from the cortex. The latter group included units with on-off, on-centre or off-centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium-speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on-centre or off-centre concentric pattern were encountered rarely; they included colour-coded fields, local-edge-detectors and one edge-inhibitory off-centre type.     

Phosphene threshold as a function of contrast of external visual stimuli

Transcranial magnetic stimulation (TMS) of the occipital lobe is frequently used to induce visual percepts by direct stimulation of visual cortex. The threshold magnetic field strength necessary to elicit a visual percept is often regarded as a measure of electrical excitability of visual cortex. Using single-pulse TMS during visual motion stimulus presentation, we investigated the relationship between different degrees of visual cortical preactivation and cortical phosphene threshold (PT). The two possible, mutually exclusive, predictions on the outcome of this experiment were that a) PT increases with stronger preactivation because of a decrease in the signal-to-noise ratio, or b) that PT decreases with increased preactivation because of the increase in neuronal response towards some threshold. PTs for single-pulse stimulation of the occipital lobe were determined for eight subjects while they passively viewed a horizontally drifting luminance-modulated sinewave grating. Gratings used were of four different luminance contrasts while the spatial and temporal frequencies remained constant. PTs were shown to increase significantly as the background grating increased in contrast. These results suggest that the neural activity underlying the perception of a phosphene can be considered a type of signal that can be partially masked by another signal, in this case the visual cortical activation produced by passive viewing of drifting gratings.

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This revised version was published online in May 2005. The preceding version was showing a false article.     

What delay fields tell us about striate cortex

It is well known that electrical activation of striate cortex (area V1) can disrupt visual behavior. Based on this knowledge, we discovered that electrical microstimulation of V1 in macaque monkeys delays saccadic eye movements when made to visual targets located in the receptive field of the stimulated neurons. This review discusses the following issues. First, the parameters that affect the delay of saccades by microstimulation of V1 are reviewed. Second, the excitability properties of the V1 elements mediating the delay are discussed. Third, the properties that determine the size and shape of the region of visual space affected by stimulation of V1 are described. This region is called a delay field. Fourth, whether the delay effect is mainly due to a disruption of the visual signal transmitted through V1 or whether it is a disturbance of the motor signal transmitted between V1 and the brain stem saccade generator is investigated. Fifth, the properties of delay fields are used to estimate the number of elements activated directly by electrical microstimulation of macaque V1. Sixth, these properties are used to make inferences about the characteristics of visual percepts induced by such stimulation. Seventh, the disruptive effects of V1 stimulation in monkeys and humans are compared. Eighth, a cortical mechanism to account for the disruptive effects of V1 stimulation is proposed. Finally, these effects are related to normal vision.     

Temporal properties of feedforward and feedback pathways between the thalamus and visual cortex in the ferret

This study examines the temporal properties of geniculocortical and corticogeniculate (CG) pathways that link the lateral geniculate nucleus (LGN) and primary visual cortex in the ferret. Using electrical stimulation in the LGN to evoke action potentials in geniculocortical and CG axons, results show that conduction latencies are significantly faster in geniculocortical neurons than in CG neurons. Within each pathway, axonal latency and visual physiology support the view of sub-classes of neurons. By examining the timing of visual responses and the latency of CG feedback, estimates indicate that visual information can reach the cortex and return to the LGN as early as 60 msec following the onset of a visual stimulus. These findings place constraints on the functional role of corticogeniculate feedback for visual processing.     

Visual training paired with electrical stimulation of the basal forebrain improves orientation-selective visual acuity in the rat

The cholinergic afferents from the basal forebrain to the primary visual cortex play a key role in visual attention and cortical plasticity. These afferent fibers modulate acute and long-term responses of visual neurons to specific stimuli. The present study evaluates whether this cholinergic modulation of visual neurons results in cortical activity and visual perception changes. Awake adult rats were exposed repeatedly for 2 weeks to an orientation-specific grating with or without coupling this visual stimulation to an electrical stimulation of the basal forebrain. The visual acuity, as measured using a visual water maze before and after the exposure to the orientation-specific grating, was increased in the group of trained rats with simultaneous basal forebrain/visual stimulation. The increase in visual acuity was not observed when visual training or basal forebrain stimulation was performed separately or when cholinergic fibers were selectively lesioned prior to the visual stimulation. The visual evoked potentials show a long-lasting increase in cortical reactivity of the primary visual cortex after coupled visual/cholinergic stimulation, as well as c-Fos immunoreactivity of both pyramidal and GABAergic interneuron. These findings demonstrate that when coupled with visual training, the cholinergic system improves visual performance for the trained orientation probably through enhancement of attentional processes and cortical plasticity in V1 related to the ratio of excitatory/inhibitory inputs. This study opens the possibility of establishing efficient rehabilitation strategies for facilitating visual capacity.