A new stimulation strategy for recording electrical auditory evoked potentials in cochlear implant patients

Recording electrical auditory brainstem responses (EABR) provides clinical insight about responses of the residual post-cochlear neural system to electrical stimulation in profoundly deaf patients. A new strategy is presented for stimulating patients already implanted with a 15-electrode cochlear implant. Since the device is fully re-programmable via a RS-232 PC interface, it was possible to load a specific stimulating strategy designed to improve the spatial locus and the temporal structure of the impulse stimulation. Waves III to V emerge more clearly when this method is applied.     

Energy Efficient Neural Stimulation: Coupling Circuit Design and Membrane Biophysics

The delivery of therapeutic levels of electrical current to neural tissue is a well-established treatment for numerous indications such as Parkinson’s disease and chronic pain. While the neuromodulation medical device industry has experienced steady clinical growth over the last two decades, much of the core technology underlying implanted pulse generators remain unchanged. In this study we propose some new methods for achieving increased energy-efficiency during neural stimulation. The first method exploits the biophysical features of excitable tissue through the use of a centered-triangular stimulation waveform. Neural activation with this waveform is achieved with a statistically significant reduction in energy compared to traditional rectangular waveforms. The second method demonstrates energy savings that could be achieved by advanced circuitry design. We show that the traditional practice of using a fixed compliance voltage for constant-current stimulation results in substantial energy loss. A portion of this energy can be recuperated by adjusting the compliance voltage to real-time requirements. Lastly, we demonstrate the potential impact of axon fiber diameter on defining the energy-optimal pulse-width for stimulation. When designing implantable pulse generators for energy efficiency, we propose that the future combination of a variable compliance system, a centered-triangular stimulus waveform, and an axon diameter specific stimulation pulse-width has great potential to reduce energy consumption and prolong battery life in neuromodulation devices.     

在电子耳蜗CIS方案中语音增强算法的实现

目的：电子耳蜗是一个帮助聋人恢复听觉的装置。它根据人耳的仿生学原理,用有限个电极刺激神经以恢复聋人听觉。目前实际应用的电子耳蜗技术已经能够在安静环境下帮助聋人恢复一定的听觉。本文在使用GIS方案的基础上,采取了频谱增强的方法,以提高电子耳蜗的在噪声环境下的性能。另外采用计算机仿真及声音合成的方法,以评估耳蜗植入者听到的声音。本实验获得了比较好的试听效果。其中提出的方法对耳子耳蜗的研究和工程现实具有一定的意义。     

Efficient Universal Computing Architectures for Decoding Neural Activity

The ability to decode neural activity into meaningful control signals for prosthetic devices is critical to the development of clinically useful brain– machine interfaces (BMIs). Such systems require input from tens to hundreds of brain-implanted recording electrodes in order to deliver robust and accurate performance; in serving that primary function they should also minimize power dissipation in order to avoid damaging neural tissue; and they should transmit data wirelessly in order to minimize the risk of infection associated with chronic, transcutaneous implants. Electronic architectures for brain– machine interfaces must therefore minimize size and power consumption, while maximizing the ability to compress data to be transmitted over limited-bandwidth wireless channels. Here we present a system of extremely low computational complexity, designed for real-time decoding of neural signals, and suited for highly scalable implantable systems. Our programmable architecture is an explicit implementation of a universal computing machine emulating the dynamics of a network of integrate-and-fire neurons; it requires no arithmetic operations except for counting, and decodes neural signals using only computationally inexpensive logic operations. The simplicity of this architecture does not compromise its ability to compress raw neural data by factors greater than . We describe a set of decoding algorithms based on this computational architecture, one designed to operate within an implanted system, minimizing its power consumption and data transmission bandwidth; and a complementary set of algorithms for learning, programming the decoder, and postprocessing the decoded output, designed to operate in an external, nonimplanted unit. The implementation of the implantable portion is estimated to require fewer than 5000 operations per second. A proof-of-concept, 32-channel field-programmable gate array (FPGA) implementation of this portion is consequently energy efficient. We validate the performance of our overall system by decoding electrophysiologic data from a behaving rodent.     

一种新型植入式装置无线数据传输方法

提出了一种植入式装置无线数据传输方法,以射频电磁波作为信息传输媒介,实现体内植入式装置与体外程控仪的双向通信。文中提出的＂b it-by-b it＂遥测方式可以显著降低起搏器等植入式装置的功耗,延长其使用寿命。     

Visual advantage in deaf adults linked to retinal changes

The altered sensory experience of profound early onset deafness provokes sometimes large scale neural reorganisations. In particular, auditory-visual cross-modal plasticity occurs, wherein redundant auditory cortex becomes recruited to vision. However, the effect of human deafness on neural structures involved in visual processing prior to the visual cortex has never been investigated, either in humans or animals. We investigated neural changes at the retina and optic nerve head in profoundly deaf (N = 14) and hearing (N = 15) adults using Optical Coherence Tomography (OCT), an in-vivo light interference method of quantifying retinal micro-structure. We compared retinal changes with behavioural results from the same deaf and hearing adults, measuring sensitivity in the peripheral visual field using Goldmann perimetry. Deaf adults had significantly larger neural rim areas, within the optic nerve head in comparison to hearing controls suggesting greater retinal ganglion cell number. Deaf adults also demonstrated significantly larger visual field areas (indicating greater peripheral sensitivity) than controls. Furthermore, neural rim area was significantly correlated with visual field area in both deaf and hearing adults. Deaf adults also showed a significantly different pattern of retinal nerve fibre layer (RNFL) distribution compared to controls. Significant correlations between the depth of the RNFL at the inferior-nasal peripapillary retina and the corresponding far temporal and superior temporal visual field areas (sensitivity) were found. Our results show that cross-modal plasticity after early onset deafness may not be limited to the sensory cortices, noting specific retinal adaptations in early onset deaf adults which are significantly correlated with peripheral vision sensitivity.     

A Fully Implantable Pacemaker for the Mouse: From Battery to Wireless Power

Animal models have become a popular platform for the investigation of the molecular and systemic mechanisms of pathological cardiovascular physiology. Chronic pacing studies with implantable pacemakers in large animals have led to useful models of heart failure and atrial fibrillation. Unfortunately, molecular and genetic studies in these large animal models are often prohibitively expensive or not available. Conversely, the mouse is an excellent species for studying molecular mechanisms of cardiovascular disease through genetic engineering. However, the large size of available pacemakers does not lend itself to chronic pacing in mice. Here, we present the design for a novel, fully implantable wireless-powered pacemaker for mice capable of long-term (>30 days) pacing. This design is compared to a traditional battery-powered pacemaker to demonstrate critical advantages achieved through wireless inductive power transfer and control. Battery-powered and wireless-powered pacemakers were fabricated from standard electronic components in our laboratory. Mice (n = 24) were implanted with endocardial, battery-powered devices (n = 14) and epicardial, wireless-powered devices (n = 10). Wireless-powered devices were associated with reduced implant mortality and more reliable device function compared to battery-powered devices. Eight of 14 (57.1%) mice implanted with battery-powered pacemakers died following device implantation compared to 1 of 10 (10%) mice implanted with wireless-powered pacemakers. Moreover, device function was achieved for 30 days with the wireless-powered device compared to 6 days with the battery-powered device. The wireless-powered pacemaker system presented herein will allow electrophysiology studies in numerous genetically engineered mouse models as well as rapid pacing-induced heart failure and atrial arrhythmia in mice.     

A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI]

BACKGROUND: Left cervical vagus nerve stimulation (VNS) using the implanted NeuroCybernetic Prosthesis (NCP) can reduce epileptic seizures and has recently been shown to give promising results for treating therapy-resistant depression. To address a disadvantage of this state-of-the-art VNS device, the use of an alternative transcutaneous electrical nerve stimulation technique, designed for muscular stimulation, was studied. Functional magnetic resonance imaging (MRI) has been used to test non-invasively access nerve structures associated with the vagus nerve system. The results and their impact are unsatisfying due to missing brainstem activations. These activations, however, are mandatory for reasoning, higher subcortical and cortical activations of vagus nerve structures. The objective of this study was to test a new parameter setting and a novel device for performing specific (well-controlled) transcutaneous VNS (tVNS) at the inner side of the tragus. This paper shows the feasibility of these and their potential for brainstem and cerebral activations as measured by blood oxygenation level dependent functional MRI (BOLD fMRI). MATERIALS AND METHODS: In total, four healthy male adults were scanned inside a 1.5-Tesla MR scanner while undergoing tVNS at the left tragus. We ensured that our newly developed tVNS stimulator was adapted to be an MR-safe stimulation device. In the experiment, cortical and brainstem representations during tVNS were compared to a baseline. RESULTS: A positive BOLD response was detected during stimulation in brain areas associated with higher order relay nuclei of vagal afferent pathways, respectively the left locus coeruleus, the thalamus (left > right), the left prefrontal cortex, the right and the left postcentral gyrus, the left posterior cingulated gyrus and the left insula. Deactivations were found in the right nucleus accumbens and the right cerebellar hemisphere. CONCLUSION: The method and device are feasible and appropriate for accessing cerebral vagus nerve structures, respectively. As functional patterns share features with fMRI BOLD, the effects previously studied with the NCP are discussed and new possibilities of tVNS are hypothesised.     

Remote electrical stimulation by means of implanted rectifiers

Miniaturization of active implantable medical devices is currently compromised by the available means for electrically powering them. Most common energy supply techniques for implants--batteries and inductive couplers--comprise bulky parts which, in most cases, are significantly larger than the circuitry they feed. Here, for overcoming such miniaturization bottleneck in the case of implants for electrical stimulation, it is proposed to make those implants act as rectifiers of high frequency bursts supplied by remote electrodes. In this way, low frequency currents will be generated locally around the implant and these low frequency currents will perform stimulation of excitable tissues whereas the high frequency currents will cause only innocuous heating. The present study numerically demonstrates that low frequency currents capable of stimulation can be produced by a miniature device behaving as a diode when high frequency currents, neither capable of thermal damage nor of stimulation, flow through the tissue where the device is implanted. Moreover, experimental evidence is provided by an in vivo proof of concept model consisting of an anesthetized earthworm in which a commercial diode was implanted. With currently available microelectronic techniques, very thin stimulation capsules (diameter <500 μm) deliverable by injection are easily conceivable.     

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。     

The multiple-channel cochlear implant: the interface between sound and the central nervous system for hearing, speech, and language in deaf people-a personal perspective

The multiple-channel cochlear implant is the first sensori-neural prosthesis to effectively and safely bring electronic technology into a direct physiological relation with the central nervous system and human consciousness, and to give speech perception to severely-profoundly deaf people and spoken language to children. Research showed that the place and temporal coding of sound frequencies could be partly replicated by multiple-channel stimulation of the auditory nerve. This required safety studies on how to prevent the effects to the cochlea of trauma, electrical stimuli, biomaterials and middle ear infection. The mechanical properties of an array and mode of stimulation for the place coding of speech frequencies were determined. A fully implantable receiver-stimulator was developed, as well as the procedures for the clinical assessment of deaf people, and the surgical placement of the device. The perception of electrically coded sounds was determined, and a speech processing strategy discovered that enabled late-deafened adults to comprehend running speech. The brain processing systems for patterns of electrical stimuli reproducing speech were elucidated. The research was developed industrially, and improvements in speech processing made through presenting additional speech frequencies by place coding. Finally, the importance of the multiple-channel cochlear implant for early deafened children was established.     

Construction of implantable optical fibers for long-term optogenetic manipulation of neural circuits

In vivo optogenetic strategies have redefined our ability to assay how neural circuits govern behavior. Although acutely implanted optical fibers have previously been used in such studies, long-term control over neuronal activity has been largely unachievable. Here we describe a method to construct implantable optical fibers to readily manipulate neural circuit elements with minimal tissue damage or change in light output over time (weeks to months). Implanted optical fibers readily interface with in vivo electrophysiological arrays or electrochemical detection electrodes. The procedure described here, from implant construction to the start of behavioral experimentation, can be completed in approximately 2-6 weeks. Successful use of implantable optical fibers will allow for long-term control of mammalian neural circuits in vivo, which is integral to the study of the neurobiology of behavior.     

Treatment of spasmodic torticollis by dorsal column stimulation.

A new method is described to treat spasmodic torticollis with the implantation of a dorsal column stimulator at the C1--2 level or with transcutaneous stimulation. 22 patients were evaluated. 3 had sufficient relief to be treated with transcutaneous stimulation only. An additional 6 patients had surgically implanted dorsal column stimulators. It was empirically determined that a frequency of 800--1,100 Hz gave the best relief from torticollis. 1 patient had an excellent result; 3 have had good results; 1 had a fair result, and 1 had a poor result. An additional patient with dystonia musculorum deformans was considerably improved by the use of dorsal column stimulation.     

Simple three-program implantable muscle stimulator with optical control

We describe an implantable stimulator which is capable of producing both continuous and intermittent patterns of indirect muscle stimulation. Switching between modes is achieved remotely via a percutaneous optical link and only standard laboratory techniques are employed in the construction of the device. It has been used to assess the influence of the pattern of stimulation on type transformation of mammalian skeletal muscle.     

Subcutaneous implantable infusion device for chronic intravenous pulsatile gonadotropin-releasing hormone treatment

Preliminary data indicate the potential utility of an implantable subcutaneous device that facilitates chronic intravenous infusion of pulsatile gonadotropin-releasing hormone (GnRH) for ovulation induction. GnRH distribution curves were congruent in control monkeys and those with implanted devices. Tissue tolerance was good in this brief trial. These findings suggest that use of this or a similar implantable device be considered for chronic GnRH administration in human pulse therapy.     

Sudden failure of implantable pulse generators: cause of failure and examination.

A sudden failure of implantable pulse generators used for spinal cord stimulation occurred in two patients. To identify the cause of this failure, an intensive destructive analysis of the explanted devices was carried out. A functional diagnosis was carried out by inspecting amplitude, pulse width and frequency on each output channel of the implantable pulse generators. Later, the titanium case of the pulse generators was opened by laser cutting to minimise any additional mechanical stress during the opening procedure. The functional test for both pulse generators showed faultless behaviour. Using light and electron microscopy, hairline cracks could be identified in the electrical connection between battery and electronic circuit. In both devices, the cracks spread through the whole bond wire in the connection to the plus pole of the battery and partially also to the minus pole. The analysis showed that both devices failed by broken bond wires. The electrical connection to the battery exists just by the spring characteristic of the wires. A push to the implant causes a short-term disconnection, resulting in a power on reset of the device. Manufacturing or design issues, allowing micromotion between battery and the hybrid part, may be the reason for this problem.     

Programmed electrical stimulation and Amiodarone therapy for the control of persistent junctional tachycardia

The use of radiofrequency as a means of synchronization and stimulation does not necessitate an external lead, and thus has allowed the construction of an implantable device for long-term treatment of reentry tachycardias. The device is used along with Amiodarone therapy and can be triggered by the patient himself.     

Battery-powered miniature implant for electrical nerve stimulation.

The range of application of implantable stimulators in functional electrical stimulation (FES) for therapeutic purposes and for the restoration of lost or damaged functions has steadily grown within the last 20 years. Each time a clinically used method is improved, a new field of FES application explored or basic research conducted, animal experiments are needed to check and evaluate the findings and results. It is precisely for this use that the stimulation system described in this paper was developed. The battery-powered single-channel stimulator can be used for the excitation of motor and sensory nerves with monophasic or biphasic impulses. All parameters and functions are programmable via the bidirectional telemetry circuit. Implant programming is achieved by a laptop computer, supported by a graphical user interface, instead of by a specially designed programmer. The maximum settings of the stimulation parameters are: frequency 100 Hz, monophasic pulse duration 0.8 ms, biphasic pulse duration 1.6 ms, stimulation current 3 mA. The implant volume was reduced to 2 cm3 (length 23 mm, width 13 mm, height 7.5 mm), lowering the weight to 3.6 g. Due to this small volume the implant can be used in small animals. The power supply via battery obviates the need for transcutaneous tunneling or permanent external high-frequency senders and facilitates the keeping of the animals.     

Evaluation of Intradural Stimulation Efficiency and Selectivity in a Computational Model of Spinal Cord Stimulation

Spinal cord stimulation (SCS) is an alternative or adjunct therapy to treat chronic pain, a prevalent and clinically challenging condition. Although SCS has substantial clinical success, the therapy is still prone to failures, including lead breakage, lead migration, and poor pain relief. The goal of this study was to develop a computational model of SCS and use the model to compare activation of neural elements during intradural and extradural electrode placement. We constructed five patient-specific models of SCS. Stimulation thresholds predicted by the model were compared to stimulation thresholds measured intraoperatively, and we used these models to quantify the efficiency and selectivity of intradural and extradural SCS. Intradural placement dramatically increased stimulation efficiency and reduced the power required to stimulate the dorsal columns by more than 90%. Intradural placement also increased selectivity, allowing activation of a greater proportion of dorsal column fibers before spread of activation to dorsal root fibers, as well as more selective activation of individual dermatomes at different lateral deviations from the midline. Further, the results suggest that current electrode designs used for extradural SCS are not optimal for intradural SCS, and a novel azimuthal tripolar design increased stimulation selectivity, even beyond that achieved with an intradural paddle array. Increased stimulation efficiency is expected to increase the battery life of implantable pulse generators, increase the recharge interval of rechargeable implantable pulse generators, and potentially reduce stimulator volume. The greater selectivity of intradural stimulation may improve the success rate of SCS by mitigating the sensitivity of pain relief to malpositioning of the electrode. The outcome of this effort is a better quantitative understanding of how intradural electrode placement can potentially increase the selectivity and efficiency of SCS, which, in turn, provides predictions that can be tested in future clinical studies assessing the potential therapeutic benefits of intradural SCS.     

Investigation of the mechanisms for wireless nerve stimulation without active electrodes

Electric-field stimulation of neuronal activity can be used to improve the speed of regeneration for severed and damaged nerves. Most techniques, however, require invasive electronic circuitry which can be uncomfortable for the patient and can damage surrounding tissue. A recently suggested technique uses a graft-antenna—a metal ring wrapped around the damaged nerve—powered by an external magnetic stimulation device. This technique requires no electrodes and internal circuitry with leads across the skin boundary or internal power, since all power is provided wirelessly. This paper examines the microscopic basic mechanisms that allow the magnetic stimulation device to cause neural activation via the graft-antenna. A computational model of the system was created and used to find that under magnetic stimulation, diverging electric fields appear at the metal ring's edges. If the magnetic stimulation is sufficient, the gradients of these fields can trigger neural activation in the nerve. In-vivo measurements were also performed on rat sciatic nerves to support the modeling finding that direct contact between the antenna and the nerve ensures neural activation given sufficient magnetic stimulation. Simulations also showed that the presence of a thin gap between the graft-antenna and the nerve does not preclude neural activation but does reduce its efficacy.