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

Flexible Electronics for High-Density EMG Based Signal Acquisition for Upper Limb Myoelectric Prosthesis Control

The research detailed in this thesis is aimed at developing flexible electrodes for high-density control of an upper limb myoelectric prosthesis. Different flexible dry electrode materials (made from doped traditionally non-conductive substrates) were used and compared to titanium (which is the industry standard for EMG electrodes). We determined that conductivity measurements alone, (the current industry standard for characterizing electrical properties of materials), are not sufficient due to their complex impedance. We measured the skin electrode complex impedance and relationship with signal to noise ratio (SNR) and settling time. We show that complex skin electrode impedance is linearly related to the SNR of signals and that complex skin electrode impedance better characterizes the electrical properties of doped, traditionally non-conductive materials for physiological signal acquisition. Next we constructed a flexible high-density array with 128- contact points arranged in an 8 x 16 configuration to cover the entire residual limb. Myoelectric signals, and its relationship to derived time domain features of all 128 channels were extracted and represented as spatio-temporal values as 8 x 16 images to represent the muscle activity map of the residual limb. Thus, a traditional signal-processing problem is converted into an image processing problem. Obtaining High Density (HD) (128 channel) spatio-temporal information has significant merits which include: ability to easily identify the optimum myoelectric recording sites on a residual limb, ability to temporally study the onset and decline of a contraction, predicting the stage of contraction and, finally, ability to implement proportional control and fine motor myoelectric control

A Comparison of ICA versus genetic algorithm optimized ICA for use in non-invasive muscle tissue EMG

Includes bibliographical references.The patent developed by Dr. L. John [1] allows for the the detection of deep muscle activation through the combination of specially positioned monopolar surface Electromyography (sEMG) electrodes and a Blind Source Separation algorithm. This concept was then proved by Morowasi and John [2] in a 12 electrode prototype system around the bicep. This proof of concept showed that it was possible to extract the deep tissue activity of the brachialis muscle in the upper arm, however, the effect of surface electrode positioning and effectual number of electrodes on signal quality is still unclear. The hope of this research is to extend this work. In this research, a genetic algorithm (GA) is implemented on top of the Fast Independent Component Analysis (FastICA) algorithm to reduce the number of electrodes needed to isolate the activity from all muscles in the upper arm, including deep tissue. The GA selects electrodes based on the amount of significant information they contribute to the ICA solution and by doing so, a reduced electrode set is generated and alternative electrode positions are identified. This allows a near optimal electrode configuration to be produced for each user. The benefits of this approach are: 1.The generalized electrode array and this algorithm can select the near optimal electrode arrangement with very minimal understanding of the underlying anatomy. 2. It can correct for small anatomical differences between test subjects and act as a calibration phase for individuals. As with any design there are also disadvantages, such as each user needs to have the electrode placement specifically customised for him or her and this process needs to be conducted using a higher number of electrodes to begin with

Implantable Transducers for Neurokinesiological Research and Neural Prostheses

The objective of this thesis was to develop a family of advanced electrical and mechanical interfaces to record activity of nerves and muscles during natural movements. These interfaces have applications in basic research and may eventually be refined for used in restoring voluntary control of movement in paralyzed persons. I) A muscle length gauge was designed that is based on piezoelectric crystals attached at the ends of a fluid filled extensible tubing. The in-vivo performance of these gauges was equal to previous length gauge designs. In addition, the ultrasound based design provided for the first time a direct muscle length calibration method. 2) An innovative nerve cuff closing technique was devised that does not reqmre suture closures. The new design uses interdigitated tubes to lock the opening and fix the lumen of a nerve cuff. The cuffs were tested in long-term mammalian implants and their performance matched or surpassed previous closure designs. The nerve cuff was further redesigned to include a more compliant cuff wall and wire electrodes. 3) Floating microelectrodes previously used for central nervous system recordings were adapted for chronic use in the peripheral nervous system. These electrodes proved disappointing in terms of signal quality and longevity. The reasons for failure are thought to be of both electrical and mechanical origin. 4) An innovative silicon micromachined peripheral single unit electrode was designed and tested. In the in-vivo tests, a limited number of recording sites successfully established short-term neural interfaces. However, the quality of the electrode performance, in terms of signal amplitude and ability to discriminate single unit potentials, was insufficient. 5) Using a finite difference model, a numerical simulation of static and dynamic electrical interactions between peripheral axons and microelectrode interfaces was derived. The model consisted of resistive and capacitive elements arranged in a 3-dimensional conductive universe (two spatial dimensions and time). Models of intrafascicular fine wire or silicon based electrodes were used to record simulated propagating action potentials. It was confirmed that electrode movement affected the recorded signal amplitude and that a dielectric layer on a silicon electrode accentuated the recorded potential field. A conducting back plane facing away from axon sources did not have a significant effect on the electrode recording properties. In conclusion, several novel implantable transducers were developed for use in neurokinesiological research. A numerical simulation of the axonal potentials recorded by intrafascicular electrodes helped interpret various shortcomings found in the in-vivo electrode performance. Although not attempted in the present thesis some of the developed technologies may have potential of transferring to clinical neural prostheses applications

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

Development of a Multimodal Apparatus to Generate Biomechanically Reproducible Spinal Cord Injuries in Large Animals

Rodents are widespread animal models in spinal cord injury (SCI) research. They have contributed to obtaining important information. However, some treatments only tested in rodents did not prove efficient in clinical trials. This is probably a result of significant differences in the physiology, anatomy, and complexity between humans and rodents. To bridge this gap in a better way, a few research groups use pig models for SCI. Here we report the development of an apparatus to perform biomechanically reproducible SCI in large animals, including pigs. We present the iterative process of engineering, starting with a weight-drop system to ultimately produce a spring-load impactor. This device allows a graded combination of a contusion and a compression injury. We further engineered a device to entrap the spinal cord and prevent it from escaping at the moment of the impact. In addition, it provides identical resistance around the cord, thereby, optimizing the inter-animal reproducibility. We also present other tools to straighten the vertebral column and to ease the surgery. Sensors mounted on the impactor provide information to assess the inter-animal reproducibility of the impacts. Further evaluation of the injury strength using neurophysiological recordings, MRI scans, and histology shows consistency between impacts. We conclude that this apparatus provides biomechanically reproducible spinal cord injuries in pigs

Neurophysiological mechanisms of sensorimotor recovery from stroke

Ischemic stroke often results in the devastating loss of nervous tissue in the cerebral cortex, leading to profound motor deficits when motor territory is lost, and ultimately resulting in a substantial reduction in quality of life for the stroke survivor. The International Classification of Functioning, Disability and Health (ICF) was developed in 2002 by the World Health Organization (WHO) and provides a framework for clinically defining impairment after stroke. While the reduction of burdens due to neurological disease is stated as a mission objective of the National Institute of Neurological Disorders and Stroke (NINDS), recent clinical trials have been unsuccessful in translating preclinical research breakthroughs into actionable therapeutic treatment strategies with meaningful progress towards this goal. This means that research expanding another NINDS mission is now more important than ever: improving fundamental knowledge about the brain and nervous system in order to illuminate the way forward. Past work in the monkey model of ischemic stroke has suggested there may be a relationship between motor improvements after injury and the ability of the animal to reintegrate sensory and motor information during behavior. This relationship may be subserved by sprouting cortical axonal processes that originate in the spared premotor cortex after motor cortical injury in squirrel monkeys. The axons were observed to grow for relatively long distances (millimeters), significantly changing direction so that it appears that they specifically navigate around the injury site and reorient toward the spared sensory cortex. Critically, it remains unknown whether such processes ever form functional synapses, and if they do, whether such synapses perform meaningful calculations or other functions during behavior. The intent of this dissertation was to study this phenomenon in both intact rats and rats with a focal ischemia in primary motor cortex (M1) contralateral to the preferred forelimb during a pellet retrieval task. As this proved to be a challenging and resource-intensive endeavor, a primary objective of the dissertation became to provide the tools to facilitate such a project to begin with. This includes the creation of software, hardware, and novel training and behavioral paradigms for the rat model. At the same time, analysis of previous experimental data suggested that plasticity in the neural activity of the bilateral motor cortices of rats performing pellet retrievals after focal M1 ischemia may exhibit its most salient changes with respect to functional changes in behavior via mechanisms that were different than initially hypothesized. Specifically, a major finding of this dissertation is the finding that evidence of plasticity in the unit activity of bilateral motor cortical areas of the reaching rat is much stronger at the level of population features. These features exhibit changes in dynamics that suggest a shift in network fixed points, which may relate to the stability of filtering performed during behavior. It is therefore predicted that in order to define recovery by comparison to restitution, a specific type of fixed point dynamics must be present in the cortical population state. A final suggestion is that the stability or presence of these dynamics is related to the reintegration of sensory information to the cortex, which may relate to the positive impact of physical therapy during rehabilitation in the postacute window. Although many more rats will be needed to state any of these findings as a definitive fact, this line of inquiry appears to be productive for identifying targets related to sensorimotor integration which may enhance the efficacy of future therapeutic strategies

Olfactory Inputs Modulate Respiration-Related Activity In The Prefrontal Cortex And Fear Behavior

Voluntary control of respiration, especially via rhythmic nasal breathing, alleviates negative feelings such as fear and is used clinically to manage certain types of panic attacks. However, the neural substrates that link nasal breathing to fear circuits remains unknown. Here we show that during conditioned fear-induced freezing behavior, mice breathe at a steady rate (~4 Hz) which is strongly correlated with a predominant 4 Hz oscillation observed in the olfactory bulb and the prelimbic prefrontal cortex (plPFC), a structure critical for the expression of conditioned fear behaviors. We demonstrate anatomical and functional connectivity between the olfactory pathway and plPFC via circuit tracing and optogenetic approaches. Disrupting olfactory inputs significantly reduces the 4 Hz oscillation in the plPFC suggesting that respiration-related signals from the olfactory system play a role in entraining this fear-related signal. Surprisingly, we find that without olfactory inputs, freezing times are significantly prolonged. Collectively, our results indicate that olfactory inputs modulate rhythmic activity in fear circuits and suggest a neural pathway that may underlie the behavioral benefits of respiration-entrained olfactory signals