电子耳蜗

一、前言: 一九五七年法国Djourno在一例因胆脂瘤造成全聋和面瘫的50岁病人作面神经修复术时,将非作用电极植入颞肌,而把作用电极通过内耳前庭植入耳蜗神经,通过线圈感应方式产生电流,并让电流经插入导线和电极刺激耳蜗神经,使病人能听到声音。电流为每秒100次脉冲,每分钟间断的次数为100次,病人能感到像打板球或滚轮所发出的声音。通过传声器,病人还能察觉环境噪声和自身的语言节律。唇读能力提高,通过训练还可听懂一些单词。这可以说是首例耳蜗电极植入的报导,并从此揭开了应用电子技术模拟耳蜗功能的序幕。60年代,HUOSE,     

大鼠皮质脊髓束神经电信号的记录与分析方法研究

目的：探索皮质脊髓束（CST）电生理信号的采集记录方法,分析描述电信号的特征,从而为通过植入式微电极阵列进行信号采集的记录方法建立一定的实验基础,为将来进一步研究脊髓损伤修复与功能重建提供有价值的神经电生理基础资料。方法：使用神经信号采集处理系统（Cerebus System）,在SD大鼠的脊髓T8节段处的皮质脊髓束内通过插入微电极,记录大鼠皮质脊髓束神经电信号。利用神经信号分析软件Offline Sorter、Neuroexplorer对已存储的信号文件进行波形特点的描述,包括波长、波幅、放电频率、同一电极上记录到的不同放电单元之间的同步性、两根电极上记录到的不同放电单元之间的同步性、放电信号的峰间期（ISI）分析等。结果：长时间稳定记录到连续的皮质脊髓束自发放电信号,一般在同一电极上记录到3~4个来自不同放电单位（细胞）的放电信号。皮质脊髓束自发放电信号的波形呈双向型,波宽为0.6~1.3 ms,波幅为百μV级。在多次实验状态下均能达到很高的信噪比,信号采集效果理想。经快蓝（LFB）染色确认记录电极尖端位于皮质脊髓束内。结论：本实验采用Cere-bus神经信号采集处理系统,利用记录电极可在大鼠的皮质脊髓束内较长时间稳定地记录到较为稳定的微伏级神经电信号,并可进行有意义的神经电信号特征分析,为进一步研究脊髓损伤修复与功能重建提供了有价值的神经电生理基础资料。     

利用NEMG信号AR模型参数对局部肌疲劳的研究

探讨如何利用针电极肌电信号来评价人体的肌肉疲劳。采用参数化模型的方法提取针电极肌电信号的AR模型a1参数,并对反映肌肉疲劳时间过程的a1参数进行直线拟合。实验结果发现拟合的直线变化趋势能够较好地反映肌肉的疲劳过程。     

建立“人工面神经技术”恢复周围性面瘫兔的闭眼功能

目的:建立"人工面神经技术"以恢复单侧周围性面瘫兔的眼轮匝肌闭眼功能,为周围性面瘫提供一种新的治疗手段。方法:制备单侧周围性面瘫兔,建立健侧眼轮匝肌肌电信号采集、中枢信号处理模式识别、患侧电流刺激眼轮匝肌系统。当健侧眼轮匝肌采集的肌电信号经信号识别、提取以及电脑分析判断,符合其闭眼刺激阈值时,即对人工电刺激器发出指令,由刺激电极直接作用于患侧眼轮匝肌,引起眼睑完全闭合结果:以最小电流刺激患侧眼轮匝肌,引起眼睑完全闭合刺激方式为正负矩形波,电流强度为0.30～0.50mA。结论:利用可植入式微机电技术,在单侧周围性面瘫模型建立"人工面神经反射弧",恢复患侧眼轮匝肌闭眼收缩,可维持双侧闭眼功能的对称性和同步性。     

建立“人工面神经技术”恢复周围性面瘫兔的闭眼功能

目的：建立“人工面神经技术”以恢复单侧周围性面瘫兔的眼轮匝肌闭眼功能,为周围性面瘫提供一种新的治疗手段。方法：制备单侧周围性面瘫兔,建立健侧眼轮匝肌肌电信号采集、中枢信号处理模式识别、患侧电流刺激眼轮匝肌系统。当健侧眼轮匝肌采集的肌电信号经信号识别、提取以及电脑分析判断,符合其闭眼刺激阈值时,即对人工电刺激器发出指令,由刺激电极直接作用于惠侧眼轮匝肌,引起眼睑完全闭合。结果：以最小电流刺激患侧眼轮匝肌,引起眼睑完全闭合。刺激方式为正负矩形波,电流强度为0．30～0．50mA。结论：利用可植入式微机电技术,在单侧周围性面瘫模型建立“人工面神经反射弧”,恢复患侧眼轮匝肌闭眼收缩,可维持双侧闭眼功能的对称性和同步性。     

聚3，4乙烯二氧噻吩修饰的新型碳纳米管纤维电极及其电化学性能评价

目的 植入式脑机接口在神经疾病的治疗方面已经得到了广泛应用，治疗的效果依赖于与神经组织接触的电极。与刚性材料制作的电极相比，碳基微纤维电极尺度小、生物兼容性好、组织炎症反应小，可以减少植入后的异物反应，改善神经记录信号的信噪比，可以长期保持稳定的电极特性。方法 本文设计了一种柔性碳纳米管（carbon nanotubes，CNTs）纤维电极的修饰方法，该方法采用电化学聚合的方式可以将聚3,4-乙烯二氧噻吩（poly（3,4-ethylenedioxythiophene），PEDOT）薄膜沉积到CNTs纤维电极上，作为微电极涂层。为了证明修饰涂层在电极表面具有良好的机械稳定性，对修饰电极进行了超声处理。此外，本文将PEDOT薄膜沉积到ITO玻璃上，评价了PEDOT薄膜的生物相容性。结果 恒电流方式在CNTs纤维电极表面沉积的PEDOT涂层降低了电极的电化学阻抗，提高了电极的电化学性能，且PEDOT沉积的时间越长阻抗减少的幅度越明显。对电极进行超声处理后，电极的电化学阻抗没有产生显著变化，说明超声处理后PEDOT涂层剥离较少，证明了修饰涂层在电极表面具有良好的机械稳定性。最后，细胞实验表明，PEDOT薄膜具有与ITO导电玻璃相当的细胞相容性。结论 PEDOT薄膜可以提高CNTs纤维电极的稳定性，有望提高脑机接口系统的寿命和可靠性，具有应用于长时间记录神经电信号的前景。     

自制起搏电极在心脏电生理实验中的应用研究

本文探索了自制起搏电极在心脏电生理研究中的应用,通过选择适当的材料,分为三部分制作电极：极片部分、起搏器接口部分、焊封与绝缘。最后,将电极缝合于犬的心脏进行起搏。结论是自制起搏电极应用于动物实验进行心脏电生理的研究是可行的。     

表面肌电信号的肌肉疲劳判别研究进展

肌肉在周期的收缩或静态的拉伸过程中,会渐渐进入疲劳状态,肌肉疲劳特性的研究在康复医学、运动医学领域具有重要作用。表面肌电信号是从肌肉表面通过电极记录下来的反映神经肌肉系统活动的一维时间序列非平稳生物电信号,是评价局部肌肉疲劳的有效工具。本研究从时域和频域、时频域线性方法下的测量指标和非线性方法下的指标来综述表面肌电信号的疲劳研究进展,同时比较各种方法的优缺点,并对使用表面肌电信号来判别疲劳研究做了进一步的展望。     

无线遥测和刺激技术建立兔房颤模型的探索

目的探索一种在无线遥测和刺激技术基础上的兔房颤模型的制作。方法新西兰兔皮下植入自主研发的植入式遥测刺激器,植入式遥测刺激器的制作是以TI公司（德州仪器）的MSP单片机和TI公司的RF无线收发芯片CC2250为核心开发设计。优化植入系统设计以满足新西兰兔房颤模型建立的探索实验;植入子植入新西兰兔腹部皮下,采集电极留置于左上肢和右上肢腋下皮下,两个刺激电极分别缝合于左心耳和左心房上,通过无线收发采集和刺激信号;实现利用Powerlab生理记录仪连续监测体表I导联心电信号,并通过专用计算机程序刺激软件,发放间歇（刺激2 s,暂停2 s）高频（频率20 Hz）阈上（强度2 mA,脉宽1 ms）刺激,若间歇期内出现房颤,则人为干预中止刺激,若转为窦性心律,则继续刺激。结果植入式遥测刺激器在体内可稳定工作（包括采集模拟心电信号和发放刺激）30 d,植入新西兰兔体内刺激3周后可诱导出房颤,持续时间〉48 h。结论用新西兰兔代替比格犬建立基于无线遥测和刺激基础上的房颤模型是完全可行的,同时也体现了动物福利优化和替代原则。     

微丝电极阵列的参考电极内置与外置的对比研究*

目的: 通过对比内置和外置参考电极的微丝电极阵列在记录大鼠脑神经元放电过程中的优缺点,优化微丝电极阵列的制作与埋置,为多通道电生理实时记录系统提供更加实惠、优异的媒介工具。方法: 采用镍铬合金丝、电路板、电极引脚和地线(银线)制作16通道的微丝电极阵列,通过内置(参考电极与电极阵列并列排布)或外置(参考电极与地线分别焊接在电极一侧的两端)微丝电极阵列的参考电极,观察对比两种电极在记录大鼠ACC脑区神经元放电中的区别。实验大鼠分为内置组(8只)和外置组(9只),检测指标有信噪比(n=8)、放电幅度(n=380)和放电频率(n=54)。结果: 内置与外置参考电极的微丝电极阵列均可顺利记录出大鼠ACC脑区神经元的电信号;与外置组相比,内置组的神经元电信号具有信噪比高(P＜0.05)、背景信号幅度小、受噪音干扰小,和放电幅度大(P＜0.05)的优点;锋电位放电频率没有显著差异(P＞0.05)。结论: 在记录大鼠ACC脑区神经元电活动时,内置参考电极的微丝电极阵列记录到更高信噪比、更大放电幅度的电信号,为多通道电生理技术提供更加可靠的工具。     

Selective recording of electroneurograms from the left vagus nerve of a dog during stimulation of cardiovascular or respiratory systems

Selective electroneurograms (ENGs) from superficial regions of the left vagus nerve of a dog were recorded with a 33-electrode spiral cuff (cuff) implanted on the nerve at the neck in an adult Beagle dog. The electrodes in the cuff were arranged in thirteen groups of three electrodes (GTE 1-13). To identify the relative positions of the particular nerve regions that innervated the heart and lungs, stimulating pulses (2 mA, 200 micros, 20 Hz) were individually delivered to all thirteen GTEs. It was shown that by delivering stimulating pulses to GTEs 4 and 9, heart rate, blood pressure and respiratory rate were modulated. Precisely, only when the stimuli were delivered to GTE 9, the heart rate began to fall and only when the stimuli were delivered to GTE 4 the rate of breathing decreased. To test the selectivity of recording the above-defined groups GTEs 4 and 9 and randomly chosen GTEs 1 and 7 were simultaneously used as recording GTEs while cardio-vascular or respiratory systems were stimulated by carotid artery compression, epinephrine injection and non-invasive, positive end-pressure ventilation. Results showed that stimulations elicited site-specific changes in ENG power spectra recorded from the superficial regions of the vagus nerve. Power spectrum of the ENG recorded with GTE 9, contained frequencies belonging to the neural activity elicited by compression of the carotid artery and injection of epinephrine. The power spectrum of the ENG recorded with GTE 4, contained frequencies belonging to the neural activity elicited by non-invasive, positive end-expiratory pressure ventilation. We concluded that the multi-electrode nerve cuff enables selective stimulation and recording of nerve activity from internal organs.     

Effects of almitrine on hypoglossal and phrenic electroneurograms

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight alpha-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO2, arterial PO2, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that 1) almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at approximately 1.0 mg/kg; 2) almitrine markedly increased HG and PHR ENG activity at all arterial PO2 values from 35-175 Torr; 3) almitrine increased HG and PHR ENG activity at all arterial PCO2 values from 30-70 Torr; and 4) almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.     

The effect of subthreshold prepulses on the recruitment order in a nerve trunk analyzed in a simple and a realistic volume conductor model

 The influence of subthreshold depolarizing prepulses on the threshold current-to-distance and the threshold current-to-diameter relationship of myelinated nerve fibers has been investigated. A nerve fiber model was used in combination with both a simple, homogeneous volume conductor model with a point source and a realistic, inhomogeneous volume conductor model of a monofascicular nerve trunk surrounded by a cuff electrode. The models predict that a subthreshold depolarizing prepulse will desensitize Ranvier nodes of fibers in the vicinity of the cathode and thus cause an increase in the threshold current of a subsequent pulse to activate these fibers. If the increase in threshold current of the excited node is large enough, the excitation will be accompanied by a strong hyperpolarization of adjacent nodes, preventing the propagation of action potentials in these fibers. As fibers close to the electrode are more desensitized by prepulses than more distant ones, it is possible to stimulate distant fibers without stimulating such fibers close to the electrode. Moreover, as larger fibers are more desensitized than smaller ones, smaller fibers have lower threshold currents than larger fibers up to a certain distance from the electrode. The realistic model has provided an additional condition for the application of this method to invert nerve fiber recruitment, i.e., real or virtual anodes should be close to the cathode. When using a cuff electrode for this purpose, in the case of monopolar stimulation the cuff length (determining the position of the virtual anodes) should not exceed twice the internodal length of the fibers to be blocked. Similarly, the distance between cathode and anodes should not exceed the internodal length of these fibers when stimulation is to be applied tripolarly. Received: 15 May 2000 / Accepted in revised form: 9 February 2001     

Clinical application of biological research

Salivary glands may be involved in a wide variety of diseases, which may be broadly grouped into (1) inflammatory, (2) noninflammatory, nonneoplastic and (3) neoplastic categories.Most inflammatory and noninflammatory, nonneoplastic diseases should be managed conservatively and symptomatically. The common exceptions are first-arch branchialcleft cysts and calculi.Neoplastic lesions always require resection if that is feasible. For benign tumors, simple excision with a cuff of normal tissue around it will usually suffice. The prevailing trend for treatment of malignant neoplasms is conservatism. No longer is the facial nerve routinely sacrificed. The resection done is dictated by the tumor size and the facial nerve is spared unless directly invaded. Postoperative radiation therapy is increasingly used.     

Nerve stimulation with a multi-contact cuff electrode: validation of model predictions

The recruitment characteristics of muscle selective nerve stimulation by a multi-contact nerve cuff electrode, as predicted by computer modeling, have been investigated in acute experiments on rabbits. A nerve cuff containing five or six dot electrodes was placed around the sciatic nerve in five rabbits. M-waves were recorded with wire electrodes from the lateral gastrocnemius, soleus, tibialis anterior, and extensor digitorum longus muscles. The muscle recruitment performances of three contact configurations (monopole, transverse bipole, transverse tripole) were compared. The selectivity was quantified by the recruitment of two muscles (one extensor and one flexor) in response to a particular stimulus. The results showed that only in a few cases, transverse bi- and tripolar stimulation provided a better selectivity than monopolar stimulation. Neither of the two extensors, nor of the two flexors could be stimulated separately. In accordance with the results of the modeling studies, bi- and tripolar stimulation required higher stimulus currents than monopolar stimulation, whereas maximum recruitment and slopes of recruitment curves were lower. The rabbit sciatic nerve appears to be a less suitable preparation for reproducible selectivity experiments, due to the variability in the number and size of the fascicles and their position in this nerve.     

A technique for recording from intact phrenic nerve afferents

Recent evidence has suggested that phrenic nerve afferents can influence respiratory motor drive. This paper presents a technique whereby the activity of single phrenic nerve afferents can be recorded from uncut dorsal root filaments. Cervical dorsal roots 4, 5, and 6 were exposed by dorsal laminectomy in 10 anesthetized, spontaneously breathing cats. A stimulating electrode was placed on the right whole phrenic nerve low in the neck. The animal was then placed in a spinal suspension frame. Dissection of the dorsal root filaments was performed with probes made of fine tungsten wire. Single filaments were isolated intact from the dorsal root fascicles and placed across a tungsten electrode. Fiber classification was performed by determining conduction velocity. Monopolar recordings were made from a total of 38 fibers. Tonic activity was observed in 21, respiratory-related activity was evident in 15, and two fibers were silent but could be recruited by phrenic nerve stimulation. The conduction velocities ranged from 2.2 to 103 m/s. Approximately one-half of the fibers had conduction velocities of less than 20 m/s. This technique offers a way to record the activity of diaphragm afferents while maintaining the integrity of possible reflex pathways. Application of this method should prove helpful in elucidating the possible role of the various diaphragm afferents in the control of respiratory motor drive.     

Neural prostheses in clinical applications--trends from precision mechanics towards biomedical microsystems in neurological rehabilitation.

Neural prostheses partially restore body functions by technical nerve excitation after trauma or neurological diseases. External devices and implants have been developed since the early 1960s for many applications. Several systems have reached nowadays clinical practice: Cochlea implants help the deaf to hear, micturition is induced by bladder stimulators in paralyzed persons and deep brain stimulation helps patients with Parkinson's disease to participate in daily life again. So far, clinical neural prostheses are fabricated with means of precision mechanics. Since microsystem technology opens the opportunity to design and develop complex systems with a high number of electrodes to interface with the nervous systems, the opportunity for selective stimulation and complex implant scenarios seems to be feasible in the near future. The potentials and limitations with regard to biomedical microdevices are introduced and discussed in this paper. Target specifications are derived from existing implants and are discussed on selected applications that has been investigated in experimental research: a micromachined implant to interface a nerve stump with a sieve electrode, cuff electrodes with integrated electronics, and an epiretinal vision prosthesis.     

Multielectrode spiral cuff for ordered and reversed activation of nerve fibres

In this paper we present the modelling, design, and experimental testing of a nerve cuff multielectrode system for selective activation of fibres in superficial peripheral nerve trunk regions which is capable of activating fibres in physiological order. The multielectrode system consists of 45 platinum electrodes embedded within a self-curling spiral silicone sheet organized in fifteen longitudinal groups consisting of three electrodes spaced equidistally around the circumference of the cuff. Electrodes in the centre band acted as stimulating cathodes while the two electrodes of the same group in the two outer bands were connected together and corresponded to the position of a particular cathode, serving as anodes to block the nascent action potentials by membrane hyperpolarization. The interpolar distance was 6 mm on both sides, resulting in a total cuff length of about 20 mm. The cuff was constructed with a diameter to fit the size of the dog sciatic nerve. Preliminary animal testing of the nerve cuff was performed on the sciatic nerve of a Bigley female dog. In the 45-electrode stimulation system, biphasic cathodic first pulses with quasitrapezoidal-shaped cathodic and square anodic parts were delivered through the particular group of tripolar electrodes to effect both selective stimulation of motor axons within the gastrocnemius muscle fascicle, and differential block by membrane hyperpolarization. The test was repeated using rectangular cathodic first biphasic current pulses delivered monopolarly on the central electrode of the same group while connected anodes were replaced by a common anode situated elsewhere in the surrounding tissue. In both experiments an isometric torque in the ankle joint elicited by the gastrocnemius muscle was measured and compared. It was shown that tripolar activation with quasitrapezoidal stimulation pulses elicited an isometric torque with a peak value of 0.83 Nm in 65 ms after onset of delivering stimulating pulses in comparison to the monopolar activation with rectangular biphasic pulses where the peak of the same value was observed in 45 ms after onset. Thus, the multipolar cuff stimulating monopolarly provided an effective means of activating motor axons selectively within the gastrocnemius muscle fascicle, while more physiological recruitment of the muscle fibres was evident when stimulating tripolarly.     

Axisymmetric finite element analysis of tourniquet application on limb

An axisymmetric finite element model of cuff on limb was developed. The model was used to simulate a clinical experiment by others in which the fluid pressure was measured at various points under a blood pressure cuff; the distribution of calculated hydrostatic stress was consistent with the clinical results. Simulations involving varying degrees of rounding at the edges of a tourniquet suggested that ensuring such rounding decreases maximum octahedral shear stress; this finding was consistent with studies by others using a two-dimensional physical model. The calculated stresses were highest at the tourniquet edges; this was consistent with nerve conduction and photomicrographic studies by others of damage caused by tourniquet use.     

Motion control of the ankle joint with a multiple contact nerve cuff electrode: a simulation study

The flat interface nerve electrode (FINE) has demonstrated significant capability for fascicular and subfascicular stimulation selectivity. However, due to the inherent complexity of the neuromuscular skeletal systems and nerve–electrode interface, a trajectory tracking motion control algorithm of musculoskeletal systems for functional electrical stimulation using a multiple contact nerve cuff electrode such as FINE has not yet been developed. In our previous study, a control system was developed for multiple-input multiple-output (MIMO) musculoskeletal systems with little prior knowledge of the system. In this study, more realistic computational ankle/subtalar joint model including a finite element model of the sciatic nerve was developed. The control system was tested to control the motion of ankle/subtalar joint angles by modulating the pulse amplitude of each contact of a FINE placed on the sciatic nerve. The simulation results showed that the control strategy based on the separation of steady state and dynamic properties of the system resulted in small output tracking errors for different reference trajectories such as sinusoidal and filtered random signals. The proposed control method also demonstrated robustness against external disturbances and system parameter variations such as muscle fatigue. These simulation results under various circumstances indicate that it is possible to take advantage of multiple contact nerve electrodes with spatial selectivity for the control of limb motion by peripheral nerve stimulation even with limited individual muscle selectivity. This technology could be useful to restore neural function in patients with paralysis.