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.     

Cuff电极长期植入性能初步研究

目的：研究Cuff电极长期植入性能。方法：在狗面神经颧支周围植入Cuff电极，通过这个植入电极，分别在14天、6月后提取自然发生的神经电信号，比较分析其信号的差异性；通过组织形态学的方法，在Cuff电极植人后6个月观察分析周围有电极植入的神经段落的组织形态学变化，以分析植入电极对神经的影响。结果：通过植入的Cuff电极，在电极植入后14天、6月均能提取出能反映眨眼动作发生的神经信号，所提取到的自然睁眼状态下的神经信号在幅值（RMS）和频率（MPF）方面没有明显的变化。长期植入Cuff电极的神经，未发现有明显的损伤性形态改变。结论：Cuff电极适合作为长期植入体使用。可以提取到稳定的神经电信号，对于所附着神经不会产生明显的损伤，提示这种植入电极的应用具有可逆性。     

Implantation of a newly developed direct optic nerve electrode device for artificial vision in rabbits

The purpose of this study was to investigate the surgical procedures involved in the implantation of a newly developed direct optic nerve electrode device for inducing artificial vision. The electrode device comprised seven wire stimulation electrodes and a return electrode (diameter 50?μm), one manipulation rod (diameter 100?μm), and a cylindrical silicone board (diameter 2.0?mm). The stimulation electrodes and the manipulation rod protruded through the board to allow implantation of the electrode tips into the optic disc of the rabbit eye. The surgical procedures required to insert the device into the vitreous cavity and implant the device into the optic disc were evaluated. When the electrodes were stimulated, electrically evoked potentials (EEPs) were recorded at the visual cortex. The electrode device was inserted into the vitreous cavity with no damage using a trocar through a scleral incision. The device was easily manipulated using vitreoretinal forceps in the vitreous cavity, and the electrode tips were implanted into the optic disc in a single insertion after vitrectomy. When electrical stimulation was applied, EEPs were recorded from all electrode pairs. The newly developed electrode device was inserted into the eye and implanted into the optic nerve disc smoothly and safely, suggesting that these surgical procedures are useful for our artificial vision system.     

Fabrication and evaluation of conductive elastomer electrodes for neural stimulation

This study explored the feasibility of applying nanocomposites derived from conducting organic polymers and silicone elastomers to fabricate electrodes for neural stimulation. A novel combination of nanoparticulate polypyrrole polymerized within a processable elastomeric silicone host polymer was evaluated in vitro and in vivo. The electrical properties of the elastomeric conductors were strongly dependent on their composition, and mixtures were identified that provided high and stable conductivity. Methods were developed for incorporating conductive polymer-siloxane co-polymer nanocomposite and silicone insulating polymers into thin-layered structures for simple single-poled electrode fabrication. In vitro testing revealed that the materials were stable under continuous pulsing for at least 10 days. Single contact prototype nerve cuff electrodes were fabricated and device functionality was demonstrated in vivo following acute implantation. The results of this study demonstrate the feasibility of conductive elastomers for peripheral nerve stimulating electrodes. Matching the mechanical properties of cuff electrode to those of the underlying neural tissue is expected to improve the long-term tissue response to the presence of the electrode.     

Acute and chronic implantation of coiled wire intraneural electrodes during cyclical electrical stimulation

The posterior tibial nerves of 18 rabbits were intraneurally implanted with coiled wire electrodes for up to 9 weeks to evaluate their usefulness for neuromuscular electrical stimulation. In one group an electrode was implanted and removed in one leg while the other leg was chronically implanted. A second group was chronically implanted without electrical stimulation in one leg and implanted with cyclical electrical stimulation applied through the electrode in the other leg. No significant changes in nerve conduction velocities between the time of implantation and up to 9 weeks post-implantation were observed in either the stimulated or the non-stimulated nerves. Little change in motor current threshold was observed beyond 10 days postimplantation. The nerves showed little or no histologic demyelination or denervation in most specimens, although in about 40% of the nerves, a bulbous formation of connective tissue was observed at electrode entry and exit sites with some demyelination in these regions. The spinal cords showed no histologic abnormalities in either group. The gastrocenemius and soleus muscles showed only occasional signs of denervation. One cat was implanted in both the posterior tibial and peroneal nerves of each leg for a 4-year period. Threshold current showed very little change during the implantation period. The nerves showed minimal focal demyelination at the electrode site and the muscles showed normal fibers.     

Long-term recording from the chorda tympani nerve in rats

Cuff electrodes with headcap connectors were implanted around the rat chorda tympani nerve. Whole nerve recordings under anesthesia were made from these nerves every week to chemical, thermal and tactile stimuli applied to the anterior tongue. The signal/noise ratio of these recordings was similar to acute recordings from the chorda tympani nerve, and the nerves were spontaneously active. Responses to chemical as well as thermal and mechanical stimulation of the tongue were recorded as early as 2 and 3 weeks after implantation and recordings from the same nerve were made for more than 3 months. These results have demonstrated the feasibility of making long-term chronic recordings of chemosensory activity in the chorda tympani nerve. The cuff electrode has great potential to provide correlative information between neurophysiological and behavioral data.     

Fabrication and evaluation of conductive elastomer electrodes for neural stimulation

This study explored the feasibility of applying nanocomposites derived from conducting organic polymers and silicone elastomers to fabricate electrodes for neural stimulation. A novel combination of nanoparticulate polypyrrole polymerized within a processable elastomeric silicone host polymer was evaluated in vitro and in vivo. The electrical properties of the elastomeric conductors were strongly dependent on their composition, and mixtures were identified that provided high and stable conductivity. Methods were developed for incorporating conductive polymer–siloxane co-polymer nanocomposite and silicone insulating polymers into thin-layered structures for simple single-poled electrode fabrication. In vitro testing revealed that the materials were stable under continuous pulsing for at least 10 days. Single contact prototype nerve cuff electrodes were fabricated and device functionality was demonstrated in vivo following acute implantation. The results of this study demonstrate the feasibility of conductive elastomers for peripheral nerve stimulating electrodes. Matching the mechanical properties of cuff electrode to those of the underlying neural tissue is expected to improve the long-term tissue response to the presence of the electrode.     

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     

Access of autonomic nerves through the optic canal, and their orbital distribution in man

The notion that autonomic nerves from the internal carotid plexus are transmitted to the orbit with the ophthalmic artery through the optic canal has been variously assumed, disregarded, or denied, but never demonstrated. The objective of this study was to examine the contents of the canal, identify any autonomic nerves, and follow their passage within the orbit. The soft tissues of the optic canal, and the apical tissues of the orbit were removed and examined histologically using 10 cadaver preparations. Additionally, tissues from an orbital exenteration and 10 ocular enucleation or donor specimens were prepared. Some of the latter material was examined with an electron microscope. Numerous autonomic nerves (four to 25, ranging in diameter from 23 to 130 microm) entered the orbit from the internal carotid plexus in the periosteum of the optic canal, the optic nerve dura mater, or the adventitia of the ophthalmic artery. In the orbit they advanced in the loose connective tissue covering the optic nerve dura and joined ciliary nerves close to the eye or entered the eye directly. None were observed to penetrate the dura, apart from a nerve accompanying the central retinal artery. Others were distributed with the ophthalmic artery and its branches. It is concluded that the optic canal is a regular, and often major, route for autonomic nerve distribution to the eye and orbit.     

Wavelet based analysis and characterization of the ECG signal

We present details of the modelling, design, and experimental testing of an implantable system with a monopolar half-cuff electrode for selective stimulation of fibres within certain superficial regions of the human common peroneal nerve which is capable of making a selective activation of muscles, thus contributing to strong dorsal flexion and moderate eversion of the hemiplegic foot. The development of the cuff electrode was based partly on data obtained from histological examination of human common peroneal nerves, and from previously described models of excitation of myelinated nerve fibres. The modelling objectives were to determine the electric field that would be generated within the deep peroneal branch of the nerve by a monopolar half-cuff electrode installed on the nerve behind the lateral head of the fibula. The extent of initial excitation of the nerve fibres within the superficial region of the deep peroneal branch elicited by a monopolar half-cuff electrode was predicted. In the past 6 months two systems were implanted. In both patients significant improvements of gait dynamics were observed.     

Flexible 3D carbon nanotubes cuff electrodes as a peripheral nerve interface

The cuff electrode provides a stable interface with peripheral nerves, which has been widely used in basic research and clinical practice. Currently, the cuff electrodes are limited by the planar processing of microfabrication. This paper presents a novel cuff electrode using high-aspect ratio carbon nanotubes (CNTs) integrated on a flexible biocompatible parylene. The microfabrication process unites the high quality vertical CNTs grown at high temperature with the heat sensitive parylene substrate in a highly controllable manner. The fabricated cuff electrodes have been utilized for extracellular nerve stimulation in rats. The experimental results demonstrate the proposed CNT electrode has a better performance than Pt electrode in nerve stimulation. Moreover, the effect of electrode position and stimulation frequency is demonstrated in this paper. This preliminary data indicates that flexible 3D CNTs cuff electrode provides an excellent platform for functional electrical stimulation.     

An intrafascicular electrode for recording of action potentials in peripheral nerves

We are developing a new type of bipolar recording electrode intended for implantation within individual fascicles of mammalian peripheral nerves. In the experiments reported here we used electrodes fabricated from 25 μm diameter Pt wire, 50 μm 90% Pt-10% Ir wire and 7 μm carbon fibers. The electrodes were implanted in the sciatic nerves of rats and in the ulnar nerves of cats. The signal-to-noise ratio of recorded activity induced by nonnoxious mechanical stimulation of the skin and joints was studied as a function of the type of electrode material used, the amount of insulation removed from the recording zone, and the longitudinal separation of the recording zones of bipolar electrode pairs. Both acute and short term (two day) chronic experiments were performed. The results indicate that a bipolar electrode made from Teflon^™-insulated, 25 μm diameter, 90% Pt-10% Ir wire, having a 1–2 mm long recording zone, can be used for recording of peripheral nerve activity when implanted with one wire inside the fascicle and the other lead level with the first lead, but outside the fascicle. No insulating cuff needs to be placed around the nerve trunk.     

Electric field aspects in hypoglossal nerve stimulation for obstructive sleep apnea: A bilateral electrophysiological evaluation of unilateral electrode configuration changes

Hypoglossal nerve stimulation is an established treatment option for obstructive sleep apnea in selected patients. A unilateral hypoglossal nerve stimulation system was approved a decade ago, yet the physiological effect of unilateral hypoglossal stimulation on bilateral tongue motion remains unclear. This study examined how electrode configuration, stimulation cuff position, or body mass index influenced the contralateral genioglossus electromyography (EMG) signal. Twenty-nine patients underwent three EMG recordings in a polysomnographic setting after being implanted with a unilateral hypoglossal nerve stimulator for at least 6 months. The ratio of EMG signals between the ipsi- and contralateral sides was evaluated. No difference in EMG signals was demonstrated based on electrode configurations, stimulation-cuff position, body-mass-index, or sleep apnea severity, even in patients with right tongue protrusion only. Our findings may be explained by a significant level of cross-innervation and by a smaller and less variable circumferential electric field than expected based on prior biophysical models. A patient's individual anatomy needs to be considered during therapy titration in order to achieve an optimal response.     

Artificial vision by direct optic nerve electrode (AV-DONE) implantation in a blind patient with retinitis pigmentosa

The purpose of this study was to evaluate the efficacy and safety of artificial vision by using a direct optic nerve electrode (AV-DONE) in a blind patient with retinitis pigmentosa (RP). This device, comprising three wire electrodes (0.05 mm in diameter), was implanted into the optic disc of a patient with RP with no light perception vision and the device was left implanted. Six months later, visual sensations were elicited by electrical stimulation through each electrode and the thresholds for the phosphene perception elicited by pulses of 0.25-ms duration/phase and a pulse frequency of 320 Hz were 30, 5, and 70 μA for each electrode. The phosphenes, which ranged in size from that of a match head to an apple, were round, oval, or linear, primarily yellow, and focally distributed. The area of the phosphenes changed when the electrical stimulation was supplied from different electrodes. No complications arose during the follow-up period. Localized visual sensations were produced in a blind patient with advanced RP, suggesting that our system could lead to the development of a useful visual prosthesis system.     

Spinal cord direct current stimulation: finite element analysis of the electric field and current density

Applied low-intensity direct current (DC) stimulates and directs axonal growth in models of spinal cord injury (SCI) and may have therapeutic value in humans. Using higher electric strengths will probably increase the beneficial effects, but this faces the risk of tissue damage by electricity or toxic reactions at the electrode–tissue interface. To inform the optimisation of DC-based therapeutics, we developed a finite element model (FEM) of the human cervical spine and calculated the electric fields (EFs) and current densities produced by electrodes of different size, geometry and location. The presence of SCI was also considered. Three disc electrodes placed outside the spine produced low-intensity, uneven EFs, whereas the EFs generated by the same electrodes located epidurally were about three times more intense. Changes in electrical conductivity after SCI had little effect on the EF magnitudes. Uniformly distributed EFs were obtained with five disc electrodes placed around the dura mater, but not with a paddle-type electrode placed in the dorsal epidural space. Replacing the five disc electrodes by a single, large band electrode yielded EFs > 5 mV/mm with relatively low current density (2.5 μA/mm²) applied. With further optimisation, epidural, single-band electrodes might enhance the effectiveness of spinal cord DC stimulation.     

Myelomatous involvement of the dura mater: a rare complication of multiple myeloma

A case of myelomatous involvement of the dura mater is reported. The patient presented with blurring of vision in the right visual field and left sided facial numbness. A magnetic resonance imaging scan of the head revealed extensive infiltration of the dura mater. Cerebrospinal fluid (CSF) analysis showed no plasmacytosis and although there was a raised CSF protein concentration, no paraprotein band was detected, despite the presence of serum paraprotein. The infiltration of the dura mater is likely to have arisen by spread from contiguous bone lesions, contrasting with the pattern of spread seen in myelomatous involvement of the leptomeninges, which probably occurs through haematogenous seeding of the meninges. Leptomeningeal involvement is associated with a very poor prognosis; however, this patient had a favourable response to combined chemotherapy and cranial radiotherapy, suggesting that myelomatous involvement of the dura mater should be considered as a distinct complication of myeloma.     

Long-term implantation of platinum electrodes: Effects on electrode material and nerve tissue

Electrical stimulation of nerves has become an established method in long-term treatment of patients with disturbances in the central or peripheral nervous system. This type of treatment raises questions as to the long-term consequences of implantation in terms of tissue and electrode reactions. The aim of the present study was to find out whether the structure of peripheral nerve tissue is altered after long-term contact with platinum electrodes and the way in which platinum electrodes are changed by prolonged implantation. The study was performed in six dogs which had undergone experiments in which stimulation electrodes were placed bilaterally on the carotid sinus nerves. Fibrotic changes in the nerve bundle and the perineurium were observed after 12·5 years. Accumulation of organic material on the electrode surface was revealed by Auger electron spectroscopy. The surfaces of the implanted electrodes had oxidised and had a high concentration of carbon and measurable amounts of sulphur, indicating corrosion.     

新型螺旋电极胞外选择性刺激视神经的仿真分析

目的 电刺激中枢神经系统已用于治疗一些神经病、精神病和感觉障碍.尽管在一些应用里相当成功,但现有的刺激技术不能精确地控制激活靶向神经元.提出一种形状自适应的新型螺旋电极,实现选择性刺激视神经.方法 应用COMSOL Multiphysics建立视神经和新型螺旋电极的几何模型；新型电极由起支撑和绝缘隔离作用的硅橡胶螺旋支架和嵌入支架内的铂金触点组成.引入激活函数来表征刺激效果,应用COMSOL仿真分析新型螺旋电极对视神经纤维选择性刺激的能力,并考虑电极触点位置的变化对选择性的影响.结果 假定激活函数的归一化阈值为0.1 V/m2,新型螺旋电极和传统袖套电极激活函数大于阈值的比例差异仅为1.2410％.当新型螺旋电极两端的电极触点靠近中间触点时,可以先激活细视神经纤维束,后激活粗纤维束.结论 仿真结果表明新型螺旋电极可以达到传统袖套电极的刺激效果.改变新型螺旋电极的触点位置可以实现选择性激活视神经纤维束.     

Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells.

Mast cells are involved in allergic reactions, but may also participate in neurogenic inflammation. The morphology of mast cells in rat dura mater and tongue was evaluated by histochemistry, as well as by scanning and transmission electron microscopy following unilateral trigeminal ganglion stimulation (5 min, 5 Hz, 5 ms, and 0.02, 0.1 or 1.0 mA). Mast cells in dura and tongue of normal animals were numerous, perivascular and often in close proximity to nerve fibers. After 5 min of electrical stimulation, mast cells contralateral to the stimulation showed histochemical characteristics of normal peripheral tissue mast cells (Safranin-positive), and by electron microscopy appeared homogeneous with numerous intact electron-dense granules. On the stimulated side, however, the staining characteristics of mast cells showed changes indicating progressive intracellular loss of their granular content. In addition, the total number of stainable mast cells decreased at all three stimulus intensities, but reached significance only at 0.1 and 0.02 mA. Ultrastructural evidence of granule changes consistent with secretion were observed although degranulation was not observed until 20 min after stimulation. There were no mast cell changes after electrical trigeminal stimulation in adult rats treated as neonates with capsaicin to destroy small caliber sensory afferent axons. These results suggest that mast cells may secrete in response to electrical stimulation of trigeminal axons, possibly mediated by antidromic release of neuropeptides, and may participate in the development of neurogenic inflammation.     

长期置入骶神经根刺激电极的兔组织学变化及其安全性

背景：有研究表明基于阳极阻滞技术的骶神经根刺激器能有效重建脊髓损伤兔的膀胱排尿功能,但符合此技术的刺激电极至今未见报道。 目的：设计并研制既与兔骶神经根匹配又符合阳极阻滞技术的刺激电极,观察长期植入刺激电极的兔骶神经根超微结构及病理形态学变化,评估刺激电极安全性。 方法：纳入新西兰兔30只,随机抽取10只兔切取双侧S2及S3神经前根,光镜下测量其直径后,制成与其直径相匹配的套筒型刺激电极。将剩余20只兔随机分为对照组及植入组,每组10只。植入组麻醉后将刺激电极植入S2及S3神经根前处,饲养半年后处死取材,观察植入处骶神经根超微结构变化。 结果与结论：长期植入该刺激电极后,光学显微镜下见植入组植入处骶神经根神经细胞结构保存良好,轴突无明显变性,无炎症细胞浸润及胶质瘢痕形成;透射电镜下观察,植入组髓鞘排列紧密,无脱髓鞘现象,神经元无核萎缩、核凹陷和异染色质增多等现象。免疫组织化学染色显示,与对照组相比,植入组植入处神经根中胶质纤维酸性蛋白、Bax,Bcl-2和Caspase-3蛋白表达差异无显著性意义。结果说明实验成功研制了兔骶神经根刺激电极,长期植入骶神经根未出现组织病理学改变及无细胞凋亡现象,安全性好。