No description available.

Restoring vision to the blind has been an objective of several research teams for a number of years. It is known that spots of light -- phosphenes -- can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this, however, our understanding of prosthetic vision remains rudimentary. To advance the realisation of a clinically viable prosthesis for the blind, a versatile integrated circuit neurostimulator was designed, manufactured, and verified. The neurostimulator provides electrical stimuli to surviving neurons in the visual pathway, affording blind patients some form of patterned vision; besides other benefits (independence), this limited vision would let patients distinguish between day and night (resetting their circadian rhythm). This thesis presents the development of the neurostimulator, an interdisciplinary work bridging engineering and medicine. Features of the neurostimulator include: high-voltage CMOS transistors in key circuits, to prevent voltage compliance issues due to an unknown or changing combined tissue and electrode/tissue interface impedance; simultaneous stimulation using current sources and sinks, with return electrodes configured to provide maximum charge containment at each stimulation site; stimuli delivered to a two dimensional mosaic of hexagonally packed electrodes, multiplexing current sources and sinks to allow each electrode in the whole mosaic to become a stimulation site; electrode shorting to remove excess charge accumulated during each stimulation phase. Detailed electrical testing and characterisation verified that the neurostimulator performed as specified, and comparable to, or better than, other vision prostheses neurostimulators. In addition, results from several animal experiments verified that the neurostimulator can elicit electrically evoked visual responses. The features of the neurostimulator enable research into how simultaneous electrical stimulation affects the visual neural pathways; those research results could impact other neural prosthetics research and devices.

Neural prostheses (NPs) are electronic stimulators that activate nerves to restore sensory or motor functions. Surface NPs are non-invasive and inexpensive, but are often poorly selective, activating non-targeted muscles and cutaneous sensory nerves that can cause pain or discomfort. Implanted NPs are highly selective, but invasive and costly. The stimulus router system (SRS) is a novel NP consisting of fully implanted leads that capture and route some of the current flowing between a pair of surface electrodes to the vicinity of a target nerve. One end of an SRS lead has a pick-up terminal that is implanted subcutaneously under the location of a surface electrode and the other end has a delivery terminal that is secured on or near the target nerve. The studies presented in this thesis address the development of the SRS from animal testing to its implementation as an upper extremity NP in a tetraplegic subject. Chapters 2 and 3 describe the SRSs basic properties, provide proof-of-principle of the system in animal studies and identify aspects that maximize its performance as a motor NP. The studies showed that selective and graded activation of deep-lying nerves can be achieved with the SRS over the full physiological range. Long term reliability of the system was demonstrated in chronic animal studies. The surface current needed to activate nerves with a SRS was found to depend on the proximity of the delivery terminal(s) to the target nerve, contact areas of the surface electrodes and implanted terminals, electrode configuration and the distances from the surface anode to the surface cathode and delivery terminal. Chapter 4 describes the first human proof-of-principle of the SRS during an intra-operative test. Finally, Chapter 5 describes the implementation of the SRS for restoration of hand function in a tetraplegic subject. Stimulation parameters and force elicited through the SRS, along with usage of the device were monitored up to 10 months after implantation. The system was found to be useful, reliable and robust. It is argued that the results of these studies indicate that the SRS provides the basis for a new family of NPs.

No description available.

Restoring vision to the blind has been an objective of several research teams for a number of years. It is known that spots of light -- phosphenes -- can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this, however, our understanding of prosthetic vision remains rudimentary. To advance the realisation of a clinically viable prosthesis for the blind, a versatile integrated circuit neurostimulator was designed, manufactured, and verified. The neurostimulator provides electrical stimuli to surviving neurons in the visual pathway, affording blind patients some form of patterned vision; besides other benefits (independence), this limited vision would let patients distinguish between day and night (resetting their circadian rhythm). This thesis presents the development of the neurostimulator, an interdisciplinary work bridging engineering and medicine. Features of the neurostimulator include: high-voltage CMOS transistors in key circuits, to prevent voltage compliance issues due to an unknown or changing combined tissue and electrode/tissue interface impedance; simultaneous stimulation using current sources and sinks, with return electrodes configured to provide maximum charge containment at each stimulation site; stimuli delivered to a two dimensional mosaic of hexagonally packed electrodes, multiplexing current sources and sinks to allow each electrode in the whole mosaic to become a stimulation site; electrode shorting to remove excess charge accumulated during each stimulation phase. Detailed electrical testing and characterisation verified that the neurostimulator performed as specified, and comparable to, or better than, other vision prostheses neurostimulators. In addition, results from several animal experiments verified that the neurostimulator can elicit electrically evoked visual responses. The features of the neurostimulator enable research into how simultaneous electrical stimulation affects the visual neural pathways; those research results could impact other neural prosthetics research and devices.

Les travaux menés au cours de cette thèse portent sur la microfabrication d'interfaces neuro-électroniques pour des applications en neurosciences. Nous avons choisi de nos focaliser sur la réhabilitation fonctionnelle motrice et sensorielle en développant différentes matrices de micro-électrodes (MEA) respectivement, des sondes neuronales rigides et des implants rétiniens souples. Selon les applications visées, deux types de substrats ont été utilisés pour concevoir ces MEA. Pour des analyses ou expériences in-vitro, les MEA (sondes neuronales) ont plutôt été réalisées sur des substrats rigides tels que le silicium ou le verre, tandis que pour les expériences in-vivo, les MEA (implants rétiniens) ont été réalisées sur des substrats souples tels que des polymères biocompatibles (polyimide ou parylène). Ces MEA ont été fabriquées avec différents matériaux d'électrodes (diamant dopé, platine, platine noir et or) qui ont également été testés afin de déterminer leur capacité en enregistrement et/ou stimulation. De plus, à l'aide de travaux de modélisation numérique, nous avons validé le concept d'une géométrie tridimensionnelle avec grille de masse permettant une stimulation plus focale des cellules. Cette thèse a ainsi contribué à stabiliser différents procédés de fabrication pour obtenir des MEA plus reproductibles ainsi que pour améliorer leur rendement. Elle a également permis d'établir un suivi et un protocole expérimental pour assurer une traçabilité des MEA et contrôler leur performances à toutes les étapes : depuis leur fabrication au moyen de techniques électrochimiques (CV, EIS) jusqu'aux expériences biologiques in-vitro et in-vivo / The work lead during this thesis deals with microfabrication of neuro-electronic interfaces for neuroscience applications. We have chosen to focus on motor and sensory function rehabilitations by developing Micro-Electrode Arrays (MEA) respectively, rigid neural probes and flexible retinal implants. According to the targeted applications, two types of substrates have been used to achieve these MEA. For analysis or in vitro experiments, neural probes MEA have been realized on rigid substrates such as silicon or glass whereas for in-vivo experiments, retinal implants MEA have been realized on flexible substrates such as biocompatible polymers (polyimide or parylene). These MEA were made with different electrode materials (boron doped diamond, platinum, black platinum and gold) which have been tested to determine their capability in recording and/or stimulation. Moreover, with numerical modelling work, we have validated a tridimensional geometry concept with a ground grid which permits a more local stimulation of cells. This thesis has contributed to stabilize different fabrication processes to obtain more repeatable MEA and also to improve their yield. It also allowed the set-up of a follow-up and an experimental protocol to insure MEA traceability and to monitor their performances at each step since their fabrication through means of electrochemical techniques (CV, EIS) to in vitro and in-vivo biological experiments

Many people around the world suffer from neurological injuries of various sorts that cause serious difficulties in their lives, due to the loss of important sensory and motor functions. Functional electrical stimulation (FES) provides a possible solution to these difficulties by means of a feedback connection allowing the target organ (or organs) to be controlled by electrical stimulation. The control signals can be provided using recorded data extracted from the nerves (electroneurogram, ENG). The most common and safe approaches for interfacing with nerves is called cuff electrodes which deliver the required feedback path for the implantable system with minimum risk. The amount of recorded information can be improved by increasing the number of electrodes within a single cuff known as multi-electrode cuffs (MECs) configuration. This strategy can increase the signal to noise ratio for the recorded signals which have typically very low amplitude (less than 5μV). Consequently multiple high gain amplifiers are used in order to amplify the signals and supply a multi-channel recorded data stream for signal processing or monitoring applications. The signal processing unit within the implantable system or outside the body is employed for classification and sorting the action potential signals (APs) depending on their conduction velocities. This method is called velocity selective recording (VSR). Basically, the idea of this approach is that the conduction velocity of AP can be determined by timing the appearance of the signal at two or more points along the nerve and then dividing the distance between the points by the delay. The purpose of this thesis to investigate an alternative approach using artificial network for APs detection and extraction in neural recording applications to increase the velocity selectivity based on VSR using MECs. The prototype systems impose four major requirements which are high velocity selectivity, small size, low power consumption and high reliability. The proposed method has been developed for applications which require online AP classification. A novel time delay neural network (TDNN) approach is used to decompose the recorded data into several matched velocity bands to allow for individual velocity selectivity at each band to be increased. Increasing the velocity selectivity leads to more accurate recording from the target fibre (or fibres) within the nerve bundle which can be used for applications that require AP classification such as bladder control and the adjustment of foot drop. The TDNN method was developed to obtain more information from an individual cuff without increasing the number of electrodes or the sampling rate. Moreover, the optimization of the hardware implementation for the proposed signal processing method permits savings in power consumption and silicon area. Finally, a nerve signal synthesiser and noise generator for the evaluation of the VSRmethod is described. This system generates multiple artificial AP signals with a time offset between the channels with additive white Gaussian noise (AWGN) to simulate the MEC and hence reduce the cost and the number of the animals required for experimental tests.

Neural prostheses are being developed to provide motor capabilities to patients who suffer from motor-debilitating diseases and conditions. These brain-computer interfaces (BCI) will be controlled by activity from the brain and bypass damaged parts of the spinal cord or peripheral nervous system to re-establish volitional control of motor output. Spike sorting is a technologically expensive component of the signal processing chain required to interpret population spike activity acquired in a BCI. No systematic analysis of the need for spike sorting has been carried out and little is known about the effects of spike sorting error on the ability of a BCI to decode intended motor commands. We developed a theoretical framework and a modelling environment to examine the effects of spike processing on the information available to a BCI decoder. Shannon information theory was applied to simulated neural data. Results demonstrated that reported amounts of spike sorting error reduce mutual information (MI) significantly in single-unit spike trains. These results prompted investigation into how much information is available in a cluster of pooled signals. Indirect information analysis revealed the conditions under which pooled multi-unit signals can maintain the MI that is available in the corresponding sorted signals and how the information loss grows with dissimilarity of MI among the pooled responses. To reveal the differences in non-sorted spike activity within the context of a BCI, we simulated responses of 4 neurons with the commonly observed and exploited cosine-tuning property and with varying levels of sorting error. Tolerances of angular tuning differences and spike sorting error were given for MI loss due to pooling under various conditions, such as cases of inter- and/or intra-electrode differences and combinations of various mean firing rates and tuning depths. These analyses revealed the degree to which mutual information loss due to pooling spike activity depended upon differences in tuning between pooled neurons and the amount of spike error introduced by sorting. The theoretical framework and computational tools presented in this dissertation will BCI system designers to make decisions with an understanding of the tradeoffs between a system with and without spike sorting. / Dissertation

<p>This dissertation is about the first substantial restoration of human sense using a medical intervention. In particular, the development of the modern cochlear implant (CI) is described, with a focus on sound processors for CIs. As of October 2015, more than 460 thousand persons had each received a single CI on one side or bilateral CIs for both sides. More than 75 percent of users of the present-day devices use the telephone routinely, including conversations with previously unknown persons and with varying and unpredictable topics. That ability is a long trip indeed from severe or worse losses in hearing. The sound processors, in conjunction with multiple sites of highly-controlled electrical stimulation in the cochlea, made the trip possible.</p><p>Many methods and techniques were used in the described research, including but not limited to those of signal processing, electrical engineering, neuroscience, speech science, and hearing science. In addition, the results were the products of collaborative efforts, beginning in the late 1970s. For example, our teams at the Duke University Medical Center and the Research Triangle Institute worked closely with investigators at 27 other universities worldwide. </p><p>The most important outcome from the research was unprecedented levels of speech reception for users of CIs, which moved a previously experimental treatment into the mainstream of clinical practice.</p> / Dissertation

No description available.