Thomas Stieglitz

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

Abstract  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 strategies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.

Attentional stimulus selection through selective synchronization between monkey visual areas.

A central motif in neuronal networks is convergence, linking several input neurons to one target neuron. In visual cortex, convergence renders target neurons responsive to complex stimuli. Yet, convergence typically sends multiple stimuli to a target, and the behaviorally relevant stimulus must be selected. We used two stimuli, activating separate electrocorticographic V1 sites, and both activating an electrocorticographic V4 site equally strongly. When one of those stimuli activated one V1 site, it gamma synchronized (60-80 Hz) to V4. When the two stimuli activated two V1 sites, primarily the relevant one gamma synchronized to V4. Frequency bands of gamma activities showed substantial overlap containing the band of interareal coherence. The relevant V1 site had its gamma peak frequency 2-3 Hz higher than the irrelevant V1 site and 4-6 Hz higher than V4. Gamma-mediated interareal influences were predominantly directed from V1 to V4. We propose that selective synchronization renders relevant input effective, thereby modulating effective connectivity.

Restoring Natural Sensory Feedback in Real-Time Bidirectional Hand Prostheses

A multigrasp, bidirectional hand prosthesis delivers dynamic sensory feedback, allowing a user with a hand amputation to achieve fine grasping force control and realistic object sensing. An Artificial Hand’s Sense of Touch To feel the hard curvature of a baseball or the soft cylinder that is a soda can—these sensations we often take for granted. But amputees with a prosthetic arm know only that they are holding an object, the shape and stiffness discernible only by eye or from experience. Toward a more sophisticated prosthetic that can “feel” an object, Raspopovic and colleagues incorporated a feedback system connected to the amputee’s arm nerves, which delivers sensory information in real time. The authors connected electrodes in the arm nerves to sensors in two fingers of the prosthetic hand. To “feel” an object, the electrodes delivered electrical stimuli to the nerves that were proportional to the finger sensor readouts. To grasp an object and perform other motor commands, muscle signals were decoded. This bidirectional hand prosthetic was tested in a single amputee who was blindfolded and acoustically shielded to assure that sound and vision were not being used to manipulate objects. In more than 700 trials, the subject showed that he could modulate force and grasp and identify physical characteristics of different types of objects, such as cotton balls, an orange, and a piece of wood. Such sensory feedback with precise control over a hand prosthetic would allow amputees to more freely and naturally explore their environments. Hand loss is a highly disabling event that markedly affects the quality of life. To achieve a close to natural replacement for the lost hand, the user should be provided with the rich sensations that we naturally perceive when grasping or manipulating an object. Ideal bidirectional hand prostheses should involve both a reliable decoding of the user’s intentions and the delivery of nearly “natural” sensory feedback through remnant afferent pathways, simultaneously and in real time. However, current hand prostheses fail to achieve these requirements, particularly because they lack any sensory feedback. We show that by stimulating the median and ulnar nerve fascicles using transversal multichannel intrafascicular electrodes, according to the information provided by the artificial sensors from a hand prosthesis, physiologically appropriate (near-natural) sensory information can be provided to an amputee during the real-time decoding of different grasping tasks to control a dexterous hand prosthesis. This feedback enabled the participant to effectively modulate the grasping force of the prosthesis with no visual or auditory feedback. Three different force levels were distinguished and consistently used by the subject. The results also demonstrate that a high complexity of perception can be obtained, allowing the subject to identify the stiffness and shape of three different objects by exploiting different characteristics of the elicited sensations. This approach could improve the efficacy and “life-like” quality of hand prostheses, resulting in a keystone strategy for the near-natural replacement of missing hands.

Micromachined, Polyimide-Based Devices for Flexible Neural Interfaces

Micromachining technologies were established to fabricate microelectrode arrays and devices for interfacing parts of the central or peripheral nervous system in case of neuronal disorders. The devices were part of a neural prosthesis that allows simultaneous multichannel recording and multisite stimulation of neurons. Overcoming the brittle mechanics of silicon, we established a process technology to fabricate light-weighted and highly flexible polyimide based devices. Concerning the challenging housing demands close to the nerve to prevent mechanical induced nerve traumatization, we integrated interconnects to decouple the nerve interface from plugs and signal processing electronics. Hybrid integration with a new assembling technique—the MicroFlex interconnection (MFI)—has been applied for the connection of the flexible microsystems to silicon microelectronics. In this paper, we present different shapes and applications of the flexible electrodes: sieve electrodes for regeneration studies, cuff electrodes for interfacing peripheral nerves, and a retina implant for ganglion cell stimulation. The discussion is focused on electrode and material properties and the hybrid assembly of a fully implantable neural prosthesis.

A MEMS-based flexible multichannel ECoG-electrode array.

We present a micromachined 252-channel ECoG (electrocorticogram)-electrode array, which is made of a thin polyimide foil substrate enclosing sputtered platinum electrode sites and conductor paths. The array subtends an area of approximately 35 mm by 60 mm and is designed to cover large parts of a hemisphere of a macaque monkeys cortex. Eight omnetics connectors are directly soldered to the foil. This leads to a compact assembly size which enables a chronic implantation of the array and allows free movements of the animal between the recording sessions. The electrode sites are 1 mm in diameter and were characterized by electrochemical impedance spectroscopy. At 1 kHz, the electrode impedances vary between 1.5 kOmega and 5 kOmega. The yield of functioning electrodes in three assembled devices is 99.5%. After implantation of a device with 100% working electrodes, standard electrocorticographic signals can be obtained from every electrode. The response to visual stimuli can be measured with electrodes lying on the visual cortex. After an implantation time of 4.5 months, all electrodes are still working and no decline in signal quality could be observed.

Polyimide cuff electrodes for peripheral nerve stimulation.

This paper describes a new tripolar spiral cuff electrode, composed of a thin (10 microm) and flexible polyimide insulating carrier and three circumneural platinum electrodes, suitable for stimulation of peripheral nerves. The cuffs were implanted around the sciatic nerve of two groups of ten rats each, one in which the polyimide ribbon was attached to a plastic connector to characterize the in vivo stimulating properties of the electrode, and one without a connector for testing possible mechanical nerve damage by means of functional and histological methods. The polyimide cuff electrodes induced only a very mild foreign body reaction and did not change the nerve shape over a 2-6 month implantation period. There were no changes in the motor and sensory nerve conduction tests, nociceptive responses and walking track pattern over follow-up, and no morphological evidence of axonal loss or demyelination, except in one case with partial demyelination of some large fibers after 6 months. By delivering single electrical pulses through the cuff electrodes graded recruitment curves of alpha-motor nerve fibers were obtained. Recruitment of all motor units was achieved with a mean charge density lower than 4 microC/cm(2) for a pulse width of 50 micros at the time of implantation as well as 45 days thereafter. These data indicate that the polyimide cuff electrode is a stable stimulating device, with physical properties and dimensions that avoid nerve compression or activity-induced axonal damage.

Implantable biomedical microsystems for neural prostheses

In the following article, the technologies to fabricate polyimide-based thin and flexible substrates with monolithically integrated electrode arrays and printed circuit boards (PCB) for hybrid electronic assemblies as well as an assembling technique that connects bare electronic dice with flexible PCBs are presented. The concept of modular, flexible biomedical microsystems as neural prostheses is introduced in general and described in detail in three examples. A cuff electrode with integrated multiplexer circuitry and standard implantable cables represents the combination of microtechnology with precision mechanics; a sieve electrode used as an implant in peripheral nerve regeneration studies demonstrates the next level of integration density but still uses a cable connection; and last, joint effort to fabricate the demonstrator of a vision prosthesis that is completely implantable in the eye with a wireless link for energy supply and data transmission is presented. System design, hybrid assembling technology, and flexible multilayer encapsulation using parylene and silicone rubber are the key components for creating a new generation of neural prostheses for complex and challenging new applications.

A flexible, light-weight multichannel sieve electrode with integrated cables for interfacing regenerating peripheral nerves

Abstract It has been shown previously that peripheral nerve axons regenerate through microvias in silicon devices. A major challenge in the design of a biocompatible interface is to establish a reliable electrical and mechanical interconnection to signal-processing and transmission electronics which allows simultaneous multichannel recordings or stimulation of nerves. This paper describes the on-going work of developing a new generation of flexible and extremely light-weight electrode arrays with integrated cables. A process technology has been established to fabricate a multilayer device with micromachining methods, which overcomes the ‘classical’ separation of substrate and insulation layers. The micromachined electrodes exhibit promising mechanical stability and high insulation resistance.

Characterization of parylene C as an encapsulation material for implanted neural prostheses

The applicability of parylene C as an encapsulation material for implanted neural prostheses was characterized and optimized. The adhesion of parylene C was tested on different substrate materials, which were commonly used in neural prostheses and the efficiency of different adhesion promotion methods was investigated. On Si(3)N(4), platinum, and on a first film of parylene C, a satisfactory adhesion was achieved with Silane A-174, which even withstood standard steam sterilization. The adhesion to gold and polyimide could not be improved sufficiently with the tested methods. Furthermore, tensile tests and measurements of the degree of crystallinity were performed on untreated, on steam sterilized, and on annealed parylene C layers to investigate the influence of thermal treatment. This led to more brittle and stiffer films due to an increase in the crystalline portion in the parylene layers. Finally, an electrochemical impedance spectroscopy was used to test if a parylene C layer was able to protect a metallic structure against corrosion on a Si(3)N(4) substrate. The results indicated that this could be only possible by treating the substrate with Silane A-174. To receive parylene C layers with a good encapsulation performance, it is important to consider the materials, which are used in the neural prosthesis, to find the best suited process parameters.

Comparative analysis of transverse intrafascicular multichannel, longitudinal intrafascicular and multipolar cuff electrodes for the selective stimulation of nerve fascicles

The selection of a suitable nerve electrode for neuroprosthetic applications implies a trade-off between invasiveness and selectivity, wherein the ultimate goal is achieving the highest selectivity for a high number of nerve fascicles by the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME) is intended to be transversally inserted into the peripheral nerve and to be useful to selectively activate subsets of axons in different fascicles within the same nerve. We present a comparative study of TIME, LIFE and multipolar cuff electrodes for the selective stimulation of small nerves. The electrodes were implanted on the rat sciatic nerve, and the activation of gastrocnemius, plantar and tibialis anterior muscles was recorded by EMG signals. Thus, the study allowed us to ascertain the selectivity of stimulation at the interfascicular and also at the intrafascicular level. The results of this study indicate that (1) intrafascicular electrodes (LIFE and TIME) provide excitation circumscribed to the implanted fascicle, whereas extraneural electrodes (cuffs) predominantly excite nerve fascicles located superficially; (2) the minimum threshold for muscle activation with TIME and LIFE was significantly lower than with cuff electrodes; (3) TIME allowed us to selectively activate the three tested muscles when stimulating through different active sites of one device, both at inter- and intrafascicular levels, whereas selective activation using multipolar cuff (with a longitudinal tripolar stimulation configuration) was only possible for two muscles, at the interfascicular level, and LIFE did not activate selectively more than one muscle in the implanted nerve fascicle.