Electrical stimulation of excitable tissue: design of efficacious and safe protocols.

Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strate- gies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

Brain responses to micro-machined silicon devices.

Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for percutaneous intravascular delivery of pulsed electric fields to achieve such neuromodulation.

Methods and apparatus for renal neuromodulation

▪ Abstract Paralyzed or paretic muscles can be made to contract by applying electrical currents to the intact peripheral motor nerves innervating them. When electrically elicited muscle contractions are coordinated in a manner that provides function, the technique is termed functional electrical stimulation (FES). In more than 40 years of FES research, principles for safe stimulation of neuromuscular tissue have been established, and methods for modulating the strength of electrically induced muscle contractions have been discovered. FES systems have been developed for restoring function in the upper extremity, lower extremity, bladder and bowel, and respiratory system. Some of these neuroprostheses have become commercialized products, and others are available in clinical research settings. Technological developments are expected to produce new systems that have no external components, are expandable to multiple applications, are upgradable to new advances, and are controlled by a combination of signals, ...

https://www.annualreviews.org/doi/pdf/10.1146/annurev.bioeng.6.040803.140103

Functional electrical stimulation for neuromuscular applications

Nerve-based stimulating electrodes provide the technology for advancing the function of motor system neural prostheses. The goal of this work was to measure and quantify the recruitment properties of a 12 contact spiral nerve cuff electrode. The cuff was implanted on the cat sciatic nerve trunk, which consists of at least four distinct motor fascicles, and the torque generated at the ankle joint by selective stimulation of the nerve was recorded in nine acute experiments. Comparisons of torques generated with the cuff to torques generated by selective stimulation of individual nerve branches indicated that the cuff allowed selective activation of individual nerve fascicles. Selectivity was dependent on the relative location of the electrode contacts and the nerve fascicles, as well as the size and relative spacing of neighboring fascicles. Selective stimulation of individual nerve fascicles allowed independent and graded control of dorsiflexion and plantarflexion torques in all nine experiments. Field steering currents improved selectivity as reflected by significant increases in the maximum torques that could be generated before spillover to other fascicles, significant increases in the difference between the current amplitude at spillover and the current amplitude at threshold, and significant increases in the slope of the current distance relationship.

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Quantification of recruitment properties of multiple contact cuff electrodes

Choice of stimulus parameters is an important consideration in the design of neural prosthetic systems. The objective of this study was to determine the effect of rectangular stimulus pulsewidth (PW) on the selectivity of peripheral nerve stimulation. Computer simulations using a cable model of a mammalian myelinated nerve fiber indicated that shorter PW's increased the difference between the threshold currents of fibers lying at different distances from an electrode. Experimental measurements of joint torque generated by peripheral nerve stimulation demonstrated that shorter PW's generated larger torques before spillover and created a larger dynamic range of currents between threshold and spillover. Thus, shorter PW's allowed more spatially selective stimulation of nerve fibers. Analysis of the response of a passive cable model to different duration stimuli indicated that PW dependent contributions of distributed sources to membrane polarization accounted for the observed differences in selectivity.

The effect of stimulus pulse duration on selectivity of neural stimulation

The objective of this study was to characterize the tissue response to multiple contact spiral nerve cuff electrodes implanted on the sciatic nerve of seven cats for 28-34 weeks. The cuffs were surrounded by fibrous tissue encapsulation consisting of foreign body cells, collagen, and fibroblasts. Focal areas of abnormal neural morphology including perineurial thickening, endoneurial fibrosis, thinly myelinated axons, and focal reduction in the density of myelinated axons were noted in five of seven nerves. In three implants, the percutaneous lead cable was destroyed by the animal pulling on the external leads. Morphological changes were observed in two of three nerves from implants sustaining no known animal induced trauma (group A), and in three of four nerves from implants damaged by the animal pulling at the leads (group B). All nerves appeared normal 2 cm proximal to the cuff. At the cuff level, small regions of one fascicle in each of two nerves (both group B) exhibited abnormalities, while the proximal and distal sections of both nerves were normal. Distal to the cuff, small regions of seven fascicles distributed among three nerves (two group A, one group B) exhibited abnormalities. These nerves were normal at the cuff level but exhibited abnormalities in individual nerve branches distal to the cuff. The incidence and characteristics of the morphological abnormalities at the cuff level are consistent with those observed in previous studies of nerve cuff electrodes, and support the hypothesis that spiral cuff electrodes can be implanted with an internal diameter less than that of the nerve and expand to accommodate the nerve without compression The pattern of morphological abnormalities indicated that mechanical trauma had occurred at some time in the past, and the distribution suggested animal intervention and the lead cable as possible causes.

Neural and connective tissue response to long‐term implantation of multiple contact nerve cuff electrodes

A self-curling elongate non-conductive sheet (A) defines a helical cuff electrode (10). A plurality of contact members (40) are linearly disposed along a direction (C) between a first layer (30) and a second layer (32) of laminated elastomeric material. The first layer is stretched along direction (F) oblique to the direction (C) before lamination such that the cuff electrode is elastomerically biased to curl into a helix. Windows (50) are defined in the elastomeric first layer (31) and bonding layer (34) to provide for electrical conduction between the contact members (40) and the nerve tissue (60) about which the cuff is wrapped. Method steps for endoscopic implantation of the cuff electrode (10) include flattening and then sliding the cuff from a carrier (100), the cuff helically self-wrapping around the nerve as it is urged from the carrier held stationary.

Implantable helical spiral cuff electrode

Systems and methods for blocking nerve impulses use an implanted electrode located on or around a nerve. A specific waveform is used that causes the nerve membrane to become incapable of transmitting an action potential. The membrane is only affected underneath the electrode, and the effect is immediately and completely reversible. The waveform has a low amplitude and can be charge balanced, with a high likelihood of being safe to the nerve for chronic conditions. It is possible to selectively block larger (motor) nerve fibers within a mixed nerve, while allowing sensory information to travel through unaffected nerve fibers.

J.T. Mortimer

Papers

Quantification of recruitment properties of multiple contact cuff electrodes

The effect of stimulus pulse duration on selectivity of neural stimulation

Neural and connective tissue response to long‐term implantation of multiple contact nerve cuff electrodes

Implantable helical spiral cuff electrode

Systems and methods for reversibly blocking nerve activity