Implantable measurement technique dedicated to the monitoring of electrode-nerve contact in bladder stimulators

A fully integrated electrode-nerve contact monitoring circuit intended to increase safety and reliability in implantable bladder stimulators is described. The proposed integrated circuit converts a measurement of the impedance of two electrode-nerve contacts into frequency. The measurement is derived from a test current generated by the stimulation current source. The obtained result is the frequency of a square wave signal. This frequency is then converted into 8-bit data, which are serially transmitted to an external controller through an inductive link. The whole circuit can be set in idle mode during stimulation, ensuring low energy consumption. It is fully testable, and an internal calibration technique makes it possible to reduce errors due to temperature and process variations. The total area of the proposed monitoring circuit is 0.1 mm² when fabricated with a 0.35μm technology, including a digitally controlled, current source. The design has been fabricated and successfully tested.     

Implantable device for long-term electrical stimulation of denervated muscles in rabbits

Although denervating injuries produce severe atrophic changes in mammalian skeletal muscle, a degree of functional restoration can be achieved through an intensive regime of electrical stimulation. An implantable stimulator was developed so that the long-term effects of different stimulation protocols could be compared in rabbits. The device, which is powered by two lithium thionyl chloride batteries, is small enough to be implanted in the peritoneal cavity. All stimulation parameters can be specified over a wide range, with a high degree of resolution; in addition, up to 16 periods of training (10–180 min) and rest (1–42 h) can be set in advance. The microcontroller-based device is programmed through a bidirectional radiofrequency link. Settings are entered via a user-friendly computer interface and annotated to create an individual study protocol for each animal. The stimulator has been reliable and stable in use. Proven technology and rigorous quality control has enabled 55 units to be implanted to date, for periods of up to 36 weeks, with only two device failures (at 15 and 29 weeks). Changes in the excitability of denervated skeletal muscles could be followed within individual animals. Chronaxie increased from 3.24±0.54 ms to 15.57±0.85 ms (n=55, p<0.0001) per phase in the 2 weeks following denervation.     

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.     

Modelling selective activation of small myelinated nerve fibres using a monopolar point electrode

The aim of this study is to investigate theoretically the possibility for activation of small myelinated nerve fibres without activating larger ones when stimulating a nerve fibre bundle using a monopolar point electrode. Therefore, the sensitivity of excitation and blocking threshold currents of nerve fibres to fibre diameter, electrode-fibre distance and pulse duration has been simulated by a computer model. A simple infinite, homogeneous volume conductor and a cathodal point source were used in combination with a model representing the electrical properties of a myelinated nerve fibre. The results show that selective activation of small myelinated fibres may be possible in a region at some distance from 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.     

Gait control system for functional electrical stimulation using neural networks

In functional electrical stimulation (FES) systems for restoring walking in spinal cord injured (SCI) individuals, hand switches are the preferred method for controlling stimulation timing. Through practice the user becomes an ‘expert’ in determining when stimulation should be applied. Neural networks have been used to ‘clone’ this expertise but these applications have used small numbers of sensors, and their structure has used a binary output, giving rise to possible controller oscillations. It was proposed that a threelayer structure neural network with continuous function, using a larger number of sensors, including ‘virtual’ sensors, can be used to ‘clone’ this expertise to produce good controllers. Using a sensor set of ten force sensors and another of 13 ‘virtual’ kinematic sensors, a good FES control system was constructed using a three-layer neural network with five hidden nodes. The sensor set comprising three sensors showed the best performance. The accuracy of the optimum three-sensor set for the force sensors and the virtual kinematic sensors was 90% and 93%, respectively, compared with 81% and 77% for a heel switch. With 32 synchronised sensors, binary neural networks and continuous neural networks were constructed and compared. The networks using continuous function had significantly fewer oscillations. Continuous neural networks offer the ability to generate good FES controllers.     

Far-field somatosensory evoked potentials in response to selective stimulation of small diameter myelinated fibers in the cat

Summary Five far-field components were identified preceding the cortical wave in response to the stimulation of the A fibers of the sural nerve. When A activity was also included in the afferent volley, a second cortical wave and additional far-field potentials were recorded. Upon blocking the A fiber activity and thus isolating the peripheral input to A fibers alone, the initial cortical wave and the far-field potentials preceding it disappeared completely, leaving the A evoked potentials intact.     

Laterality effects in selective attention to threat after repetitive transcranial magnetic stimulation at the prefrontal cortex in female subjects

Recently, several experiments have indicated that the left and right prefrontal cortex (PFC) are differently involved in emotional processing. The aim of this study was to investigate the role of the left and right PFC in selective attention to angry faces by using a pictorial emotional Stroop task. Slow repetitive transcranial magnetic stimulation (rTMS) was applied to the left and right PFC of 10 female subjects for 15 min on separate days. Results showed a significant effect of stimulation position: right PFC rTMS resulted in selective attention towards angry faces, whereas left PFC rTMS resulted in selective attention away from angry faces. This finding is in accordance with theoretical accounts of the neural implementation of approach and withdrawal systems.     

Production of elastic electrodes for nerve stimulation

For better evoking and monitoring electrical activities of visceral nerves, a elastic electrode made of conductive plastic and silicone gum is developed.     

硬膜外植入式皮质刺激脑卒中患者提高神经网络功能

背景：硬膜外植入式皮质刺激兼顾了经颅磁刺激、经颅直流电刺激、硬膜下皮质刺激和深部脑刺激的优点,可显著改善脑卒中后的肢体运动与语言功能。 目的：综述近年来有关硬膜外植入式皮质刺激在脑卒中康复中的研究及其临床应用。 方法：由第一作者应用计算机检索1995年1月至2014年4月PubMed 数据库及中国期刊全文数据库文献,检索关键词为“cortical stimulation,extradural motor cortex stimulation,extradural cortical implants,extradural cortical stimulation,stroke,rehabilitation;皮质刺激,硬膜外电刺激,硬膜外皮质植入,硬膜外皮质刺激,脑卒中,康复”。纳入有关硬膜外植入式皮质刺激在脑卒中后运动与言语障碍中应用的文章。 结果与结论：硬膜外皮质刺激是植入式皮质刺激,其优势是侵入性小、高度精确性和经硬膜与大脑密切接触,对缺乏有效治疗的脑卒中慢性期运动和语言障碍患者来说,这有可能是一种新的治疗方法。硬膜外皮质刺激通过促进神经可塑性、促进病灶周围结构与功能改变、提高神经网络功能、促进大脑半球间功能平衡及增加感觉输入来改善脑卒中后的肢体运动功能与语言功能。中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程全文链接：     

Effects of aging on neural connectivity underlying selective memory for emotional scenes

Older adults show age-related reductions in memory for neutral items within complex visual scenes, but just like young adults, older adults exhibit a memory advantage for emotional items within scenes compared with the background scene information. The present study examined young and older adults' encoding-stage effective connectivity for selective memory of emotional items versus memory for both the emotional item and its background. In a functional magnetic resonance imaging (fMRI) study, participants viewed scenes containing either positive or negative items within neutral backgrounds. Outside the scanner, participants completed a memory test for items and backgrounds. Irrespective of scene content being emotionally positive or negative, older adults had stronger positive connections among frontal regions and from frontal regions to medial temporal lobe structures than did young adults, especially when items and backgrounds were subsequently remembered. These results suggest there are differences between young and older adults' connectivity accompanying the encoding of emotional scenes. Older adults may require more frontal connectivity to encode all elements of a scene rather than just encoding the emotional item.     

Differences between otolith- and semicircular canal-activated neural circuitry in the vestibular system

In the last two decades, we have focused on establishing a reliable technique for focal stimulation of vestibular receptors to evaluate neural connectivity. Here, we summarize the vestibular-related neuronal circuits for the vestibulo-ocular reflex, vestibulocollic reflex, and vestibulospinal reflex arcs. The focal stimulating technique also uncovered some hidden neural mechanisms. In the otolith system, we identified two hidden neural mechanisms that enhance otolith receptor sensitivity. The first is commissural inhibition, which boosts sensitivity by incorporating inputs from bilateral otolith receptors, the existence of which was in contradiction to the classical understanding of the otolith system but was observed in the utricular system. The second mechanism, cross-striolar inhibition, intensifies the sensitivity of inputs from both sides of receptive cells across the striola in a single otolith sensor. This was an entirely novel finding and is typically observed in the saccular system. We discuss the possible functional meaning of commissural and cross-striolar inhibition. Finally, our focal stimulating technique was applied to elucidate the different constructions of axonal projections from each vestibular receptor to the spinal cord. We also discuss the possible function of the unique neural connectivity observed in each vestibular receptor system.     

Optimum electrode geometry for spinal cord stimulation: The narrow bipole and tripole

A computer model is used to calculate the optimum geometry of an epidural electrode, consisting of a longitudinal contact array, for spinal cord stimulation in the managmment of chronic, intractable pain. 3D models of the spinal area are used for the computation of stimulation induced fields, and a cable model of myelinated nerve fibre is used for the calculation of the threshold stimulus to excite large dorsal column and dorsal root fibres. The criteria for the geometry of the longitudinal contact array are: a low threshold for the stimulation of dorsal column fibres compared with dorsal root fibres; and a low stimulation voltage (and current). For both percutaneous and laminectomy electrodes, the contact length should be approximately 1.5 mm, and the optimum contact separation, as determined by the computer model, is 2–2.5 mm. The contacts for a laminectomy electrode should be approximately 4 mm wide. This electrode geometry is applicable to all spinal levels where the dorsal columns can be stimulated (C1-2 down to L1). The stimulating electrode should preferably be used as a tripole with one (central) cathode.     

The anatomical basis for transcutaneous auricular vagus nerve stimulation

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non-invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold’s reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the ‘gold-standard’ approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined.     

A model for transcutaneous current stimulation: simulations and experiments

Complex nerve models have been developed for describing the generation of action potentials in humans. Such nerve models have primarily been used to model implantable electrical stimulation systems, where the stimulation electrodes are close to the nerve (near-field). To address if these nerve models can also be used to model transcutaneous electrical stimulation (TES) (far-field), we have developed a TES model that comprises a volume conductor and different previously published non-linear nerve models. The volume conductor models the resistive and capacitive properties of electrodes, electrode-skin interface, skin, fat, muscle, and bone. The non-linear nerve models were used to conclude from the potential field within the volume conductor on nerve activation. A comparison of simulated and experimentally measured chronaxie values (a measure for the excitability of nerves) and muscle twitch forces on human volunteers allowed us to conclude that some of the published nerve models can be used in TES models. The presented TES model provides a first step to more extensive model implementations for TES in which e.g., multi-array electrode configurations can be tested.     

Relationship between stimulus amplitude,stimulus frequency and neural damage during electrical stimulation of sciatic nerve of cat

The relation is investigated between stimulus frequency, stimulus pulse amplitude and the neural damage induced by continuous stimulation of the cat's sciatic nerve. The chronically implanted electrodes were pulsed continuously and the effects of the electrical stimulation were quantified as the amount of early axonal degeneration (EAD) present in the nerves seven days after the continuous stimulation. The primary effect of stimulating at 100 Hz rather than 50 Hz was to cause an increase in the slope of the plot of the amount of EAD versus stimulus lower. There was a small amount of EAD in three of the nerves stimulated at 20 Hz, but there was no detectable correlation between the amount of EAD and the stimulus amplitude. This suggests that continuous electrical stimulation of peripheral nerves at a low frequency induce little or no neural damage, even if the stimulus amplitude is very high. A preliminary presentation of the results has been made elsewhere (Agnew et al., 1993)