Increasing the robustness of active upper limb prostheses

This thesis is based on my work done at the Institute for Neurorehabilitation Systems at the University Medical Center Goettingen. My work has been partially founded by German Ministry for Education and Research (BMBF) via the Bernstein Focus Neurotechnology (BFNT) Göttingen under grant number 1GQ0810 The local ethics committee approved all studies involving human subjects, and all subjects signed informed consents prior to their participation in the studies. The entire thesis has been originally written by me. Part of the materials used in this thesis have also been published in journals or conferences, where I am the first or corresponding author. All rights for re-use of previously published material were obtained. Reused figures and tables of IEEE publications are marked with © [Year] IEEE. Hereby I declare that I have written this thesis independently and with no other aids and sources than quoted

Improving the mechanistic study of neuromuscular diseases through the development of a fully wireless and implantable recording device

Neuromuscular diseases manifest by a handful of known phenotypes affecting the peripheral nerves, skeletal muscle fibers, and neuromuscular junction. Common signs of these diseases include demyelination, myasthenia, atrophy, and aberrant muscle activity—all of which may be tracked over time using one or more electrophysiological markers. Mice, which are the predominant mammalian model for most human diseases, have been used to study congenital neuromuscular diseases for decades. However, our understanding of the mechanisms underlying these pathologies is still incomplete. This is in part due to the lack of instrumentation available to easily collect longitudinal, in vivo electrophysiological activity from mice. There remains a need for a fully wireless, batteryless, and implantable recording system that can be adapted for a variety of electrophysiological measurements and also enable long-term, continuous data collection in very small animals. To meet this need a miniature, chronically implantable device has been developed that is capable of wirelessly coupling energy from electromagnetic fields while implanted within a body. This device can both record and trigger bioelectric events and may be chronically implanted in rodents as small as mice. This grants investigators the ability to continuously observe electrophysiological changes corresponding to disease progression in a single, freely behaving, untethered animal. The fully wireless closed-loop system is an adaptable solution for a range of long-term mechanistic and diagnostic studies in rodent disease models. Its high level of functionality, adjustable parameters, accessible building blocks, reprogrammable firmware, and modular electrode interface offer flexibility that is distinctive among fully implantable recording or stimulating devices. The key significance of this work is that it has generated novel instrumentation in the form of a fully implantable bioelectric recording device having a much higher level of functionality than any other fully wireless system available for mouse work. This has incidentally led to contributions in the areas of wireless power transfer and neural interfaces for upper-limb prosthesis control. Herein the solution space for wireless power transfer is examined including a close inspection of far-field power transfer to implanted bioelectric sensors. Methods of design and characterization for the iterative development of the device are detailed. Furthermore, its performance and utility in remote bioelectric sensing applications is demonstrated with humans, rats, healthy mice, and mouse models for degenerative neuromuscular and motoneuron diseases

The Use of Skeletal Muscle to Amplify Action Potentials in Transected Peripheral Nerves

Upper limb amputees suffer with problems associated with control and attachment of prostheses. Skin-surface electrodes placed over the stump, which detect myoelectric signals, are traditionally used to control hand movements. However, this method is unintuitive, the electrodes lift-off, and signal selectivity can be an issue. One solution to these limitations is to implant electrodes directly on muscles. Another approach is to implant electrodes directly into the nerves that innervate the muscles. A significant challenge with both solutions is the reliable transmission of biosignals across the skin barrier. In this thesis, I investigated the use of implantable muscle electrodes in an ovine model using myoelectrodes in combination with a bone-anchor, acting as a conduit for signal transmission. High-quality readings were obtained which were significantly better than skin-surface electrode readings. I further investigated the effect of electrode configurations to achieve the best signal quality. For direct recording from nerves, I tested the effect of adsorbed endoneural basement membrane proteins on nerve regeneration in vivo using microchannel neural interfaces implanted in rat sciatic nerves. Muscle and nerve signal recordings were obtained and improvements in sciatic nerve function were observed. Direct skeletal fixation of a prosthesis to the amputation stump using a bone-anchor has been proposed as a solution to skin problems associated with traditional socket-type prostheses. However, there remains a concern about the risk of infection between the implant and skin. Achieving a durable seal at this interface is therefore crucial, which formed the final part of the thesis. Bone-anchors were optimised for surface pore size and coatings to facilitate binding of human dermal fibroblasts to optimise skin-implant seal in an ovine model. Implants silanised with Arginine-Glycine-Aspartic Acid experienced significantly increased dermal tissue infiltration. This approach may therefore improve the soft tissue seal, and thus success of bone-anchored implants. By addressing both the way prostheses are attached to the amputation stump, by way of direct skeletal fixation, as well as providing high fidelity biosignals for high-level intuitive prosthetic control, I aim to further the field of limb loss rehabilitation

On the viability of implantable electrodes for the natural control of artificial limbs: Review and discussion

The control of robotic prostheses based on pattern recognition algorithms is a widely studied subject that has shown promising results in acute experiments. The long-term implementation of this technology, however, has not yet been achieved due to practical issues that can be mainly attributed to the use of surface electrodes and their highly environmental dependency. This paper describes several implantable electrodes and discusses them as a solution for the natural control of artificial limbs. In this context "natural" is defined as producing control over limb movement analogous to that of an intact physiological system. This includes coordinated and simultaneous movements of different degrees of freedom. It also implies that the input signals must come from nerves or muscles that were originally meant to produce the intended movement and that feedback is perceived as originating in the missing limb without requiring burdensome levels of concentration. After scrutinizing different electrode designs and their clinical implementation, we concluded that the epimysial and cuff electrodes are currently promising candidates to achieving a long-term stable and natural control of robotic prosthetics, provided that communication from the electrodes to the outside of the body is guaranteed

Neuromorphic hardware for somatosensory neuroprostheses

In individuals with sensory-motor impairments, missing limb functions can be restored using neuroprosthetic devices that directly interface with the nervous system. However, restoring the natural tactile experience through electrical neural stimulation requires complex encoding strategies. Indeed, they are presently limited in effectively conveying or restoring tactile sensations by bandwidth constraints. Neuromorphic technology, which mimics the natural behavior of neurons and synapses, holds promise for replicating the encoding of natural touch, potentially informing neurostimulation design. In this perspective, we propose that incorporating neuromorphic technologies into neuroprostheses could be an effective approach for developing more natural human-machine interfaces, potentially leading to advancements in device performance, acceptability, and embeddability. We also highlight ongoing challenges and the required actions to facilitate the future integration of these advanced technologies

Implantable Electrodes for Upper Limb Prosthetic Control

This thesis describes a study investigating implantable interfaces with muscles and peripheral nerves. Current prostheses for upper limb amputees do not provide intuitive control over hand, wrist and elbow motion. By implanting electrodes for recording and stimulating onto muscles and into nerves in the amputation stump a greater number of control signals may be made available, signals which will be used to control dextrous hand movements. An implantable epimysial interface was developed using a bone-anchored device to hard-wire signals across the skin barrier. In a single ovine model pilot study the bone-anchor was implanted transtibially and the epimysial electrode was place superficially to m. peroneus teritus. Physiological signals were obtained over 12 weeks during treadmill walking. The external connector on the bone-anchor failed at 12 weeks, correlating with a drop in signal quality in an otherwise robust interface integrated with bone and skin tissue. The ovine bone-anchor model was repeated in 6 sheep for 19 weeks, with epimysial recordings made regularly. Increasing signal quality was seen during the study and was significantly greater from implanted electrodes compared with skin surface electrodes at 19 weeks (p = 0.016). Some complications with skin-implant integration were observed in proximally located implants. Crosstalk between muscles was assessed using pre-terminal nerve stimulation, and was found to be dependent upon muscle location and innervation. The ovine m. peroneus teritus model was used to assess recovery following targeted muscle reinnervation. Muscle signal recovery was observed approximately one month after surgery correlating with the start of functional recovery (assessed by force plate analysis). These studies indicate that a suitably modified bone-anchored device may be suitable for signal transmission in human patients, providing a stable, long-term solution to both prosthesis attachment and control. The potential of nerve interfaces for prosthetic control was investigated. The microchannel neural interface (MNI) was chosen because it overcomes limitations with other neural microarray designs: signal strength; cross-talk, and the locations of Nodes of Ranvier. MNIs confine regenerating nerves to small, ∼ 100 µm diameter, insulating tubes, this increases the length within which nerve signals can be recorded and amplifies the recorded signals. However, in vivo MNIs can become occluded by fibrosis that reduces or prevents axon regeneration. Two in vitro studies of neurocompatibility were carried out to investigate strategies for improving axon regeneration within microchannels. The first in vitro study compared the effect of different adsorbed endoneurial basement membrane proteins on PC-12 cell neurite extension on silicone substrates. The optimal protein coating concentrations for poly-D-lysine, collagen-IV and laminin-2,(-4) were determined. The optimal concentrations were compared with mixtures of basement membrane proteins, the effect of mixture coating order and constitution were investigated. It was found that endoneurial BM proteins significantly enhance neurite outgrowth compared with controls. Two coatings were suggested as most suited for improving neural regeneration within microchannels: a single layer coating of 10 µg/cm2 collagen-IV; and a mixed coating of 10 µg/cm2 collagen-IV, 1 µg/cm2 laminin-2,(-4), and 0.175 µg/cm2 nidogen-1. The second in vitro study investigated the effect of grooved, roughened and multi-scale silicone surfaces on on PC-12 cell neurite extension. Deeper, narrower grooves were shown to increase the extent of neurite alignment, while resulting in fewer, longer, neurites. Roughening surfaces was shown to increase the amount of protein (collagen-IV) which adsorbed from solution and increase the number of neurites each cell extended. Surfaces with multiscale topographies synergistically increased the number and length of neurites and guided neurite growth along the groove direction. MNIs were manufactured for in vivo testing. These MNIs were used to determine the effect of adsorbed endoneurial basement membrane proteins on nerve regeneration in vivo, but the multiscale topographies were not applied during manufacturing. Four alternative manufacturing methods were investigated and iterative improvements were made to create a stacked interface with multiple microchannel layers. Microchannel layers were created by laser patterning silicone and metal foil components, followed by plasma bonding to create a 3-dimensional structure with 150 µm deep, 200 µm wide microchannels. Electrode impedances of 27.2 ± 19.8 kΩ at 1kHz were achieved by DC etching. The method overcomes some current limitations on electrode connectivity and microchannel sealing, and may improve recording capabilities over single layer designs by increasing the ratio of electrodes to microchannels. Manufactured MNIs were tested in a rat sciatic nerve transection model. Following implantation nerves were allowed to regenerate for one and two months. First, suture and fibrin glue were compared as MNI fixation methods for one month, the nerve regenerated within the fibrin glue, outside the interface lumen, therefore sutures were chosen as a long term fixation method. The influence of endoneurial basement membrane protein coatings, identified previously, on nerve regeneration with MNIs was investigated. Nerves regenerated through the MNIs over two months and began to reinnervate the distal limb. Improvements in the sciatic function index were observed over two months, with no significant differences between protein coated and control interfaces. Some weak histological evidence for the use of protein coatings was found, with axon diameters increased distal to protein coated MNIs. Electromyographic and electroneurographic recordings demonstrated similar signal amplitudes to previous studies. In order to bring the research described in this thesis to clinical practice further engineering improvements to the design and manufacture of electrodes, which utilise materials or coatings to enhance neurocompatibility, is required. Avenues for further research are discussed and additional experiments and investigations are described. By combining developments in implantable muscle and nerve interfaces with surgical techniques and improvements in neurocompatibility the promise of upper limb prosthetic control may be realised

Improving Upper Extremity Myoelectric Prosthesis Functionality Through the Use of Intramuscular EMG Signals

The prevalence of upper extremity amputation is increasing in the United States. To meet the demand of decreased functionality associated with upper extremity loss, prosthetic design has become increasingly complex, allowing for an high number of operable degrees-of-freedom (DOFs). Unfortunately, the ability to control this in- creased mechanical capability is limited. Pattern recognition using EMG signals obtained from surface electrodes is the state-of-the-art for myoelectric prosthetic con- trol; however, it is limited in its ability allow for natural, simultaneous control of multiple DOFs. Recognizing this limitation, some researchers have focused efforts on creating control algorithms based on intramuscular signals. Despite initial reports that demonstrated no improvements in the classification accuracy, more recent liter- ature presents intramuscular EMG signals as potentially useful drivers of classifying multiple, simultaneous DOFs. As opposed to surface-based signals, intramuscular signals are generated from a much smaller conduction volume, dependent on the type of electrode used. A novel combined control strategy incorporating both intramus- cular and surface EMG signals may have the potential to leverage advantages from both strategies. The research presented herein represents the first examination of complement- ing the more global signal obtained from surface electrodes with the muscle-specific information from intramuscular electrodes. When compared to control with either intramuscular or surface signals alone, a strategy involving combining information from both signal sources results in the highest degree of classification accuracy for controlling wrist rotation, flexion and hand grasps simultaneously using a 3-DOF LDA classifier. A single classifier, in which 3 DOFs are included, outperformed a par- allel classifier, in which each DOF was independently classified and all classifications combined for a single 3 DOF output. However, high classification accuracies for each individual DOF highlight the potential for using combined signals for accurate control of a prosthetic limb. The impacts of these findings are also discussed, including the implication for future prosthetic and electrode design. Additionally, a novel method for quantitatively measuring the functionality of a prosthetic user is included

Prosthetic Control and Sensory Feedback for Upper Limb Amputees

Hand amputation could dramatically degrade the life quality of amputees. Many amputees use prostheses to restore part of the hand functions. Myoelectric prosthesis provides the most dexterous control. However, they are facing high rejection rate. One of the reasons is the lack of sensory feedback. There is a need for providing sensory feedback for myoelectric prosthesis users. It can improve object manipulation abilities, enhance the perceptual embodiment of myoelectric prostheses and help reduce phantom limb pain. This PhD work focuses on building bi-directional prostheses for upper limb amputees. In the introduction chapter, first, an overview of upper limb amputee demographics and upper limb prosthesis is given. Then the human somatosensory system is briefly introduced. The next part reviews invasive and non-invasive sensory feedback methods reported in the literature. The rest of the chapter describes the motivation of the project and the thesis organization. The first step to build a bi-directional prostheses is to investigate natural and robust multifunctional prosthetic control. Most of the commerical prostheses apply non-pattern recognition based myoelectric control methods, which offers only limited functionalities. In this thesis work, pattern recognition based prosthetic control employing three commonly used and representative machine learning algorithms is investigated. Three datasets involving different levels of upper arm movements are used for testing the algorithm effectiveness. The influence of time-domain features, window and increment sizes, algorithms, and post-processing techniques are analyzed and discussed. The next three chapters address different aspects of providing sensory feedback. The first focus of sensory feedback process is the automatic phantom map detection. Many amputees have referred sensation from their missing hand on their residual limbs (phantom maps). This skin area can serve as a target for providing amputees with non-invasive tactile sensory feedback. One of the challenges of providing sensory feedback on the phantom map is to define the accurate boundary of each phantom digit because the phantom map distribution varies from person to person. Automatic phantom map detection methods based on four decomposition support vector machine algorithms and three sampling methods are proposed. The accuracy and training/ classification time of each algorithm using a dense stimulation array and two coarse stimulation arrays are presented and compared. The next focus of the thesis is to develop non-invasive tactile display. The design and psychophysical testing results of three types of non-invasive tactile feedback arrays are presented: two with vibrotactile modality and one with multi modality. For vibrotactile, two types of miniaturized vibrators: eccentric rotating masses (ERMs) and linear resonant actuators (LRAs) were first tested on healthy subjects and their effectiveness was compared. Then the ERMs are integrated into a vibrotactile glove to assess the feasibility of providing sensory feedback for unilateral upper limb amputees on the contralateral hand. For multimodal stimulation, miniature multimodal actuators integrating servomotors and vibrators were designed. The actuator can be used to deliver both high-frequency vibration and low-frequency pressures simultaneously. By utilizing two modalities at the same time, the actuator stimulates different types of mechanoreceptors and thus h