Electromyogram Interference Reduction In Neural Signal Recording Using Simple RC Compensation Circuits

Neuroprosthesis can partially restore lost motor functionalities of individuals such as bladder voiding using functional electrical stimulation (FES) techniques. FES involves applying pattern of electrical current pulses using implanted electrodes to trigger affected nerves that are damaged due to paralysis. A neural signal recorded using tripolar cuff electrodes is significantly contaminated due to the presence of EMG interference from the surrounding muscles. Conventional neural amplifiers are unable to remove such interferences and modifications to the design are required. The modification to the design of the Quasi-tripole (QT) amplifier is considered in this work to minimise the EMG interferences from neural signal recording. The analogy between this modified version of QT known as mQT and Wheatstone bridge claims to neutralise the EMG interference by adding compensation circuit to either end of the outer electrodes of the tripolar cuff and therefore balancing the bridge. In this work, we present simple 3 and 2 stage RC compensation circuits to minimise EMG interference in trying to balance the bridge in the neural frequency band of interest (500-10kHz). It is shown that simple RC compensation circuit in series reduces EMG interference only at the spot frequency rather than linearly in the entire frequency band of interest. However, two and three stages RC ladder compensation circuits mimicking electrode-electrolyte interface, can minimize the EMG interference linearly in the entire frequency band of interest, without requiring any readjustment to their components. The aim is to minimise EMG interference as close to null as possible. Invitro testing of about 20% imbalanced cuff electrode with proposed 3 and 2 stage RC ladder compensation circuits resulted in linear EMG interference reduction atleast by a factor of 6. On an average, this yielded an improvement of above 80% EMG minimisation, in contrast to above 90% observed in the optimisation results, when 1Ω transimpedance (EMG) was introduced into the setup. Further improvements to the setup and design can give more promising results in reliable neural signal recording for FES applications

VLSI Circuits for Bidirectional Neural Interfaces

Medical devices that deliver electrical stimulation to neural tissue are important clinical tools that can augment or replace pharmacological therapies. The success of such devices has led to an explosion of interest in the field, termed neuromodulation, with a diverse set of disorders being targeted for device-based treatment. Nevertheless, a large degree of uncertainty surrounds how and why these devices are effective. This uncertainty limits the ability to optimize therapy and gives rise to deleterious side effects. An emerging approach to improve neuromodulation efficacy and to better understand its mechanisms is to record bioelectric activity during stimulation. Understanding how stimulation affects electrophysiology can provide insights into disease, and also provides a feedback signal to autonomously tune stimulation parameters to improve efficacy or decrease side-effects. The aims of this work were taken up to advance the state-of-the-art in neuro-interface technology to enable closed-loop neuromodulation therapies. Long term monitoring of neuronal activity in awake and behaving subjects can provide critical insights into brain dynamics that can inform system-level design of closed-loop neuromodulation systems. Thus, first we designed a system that wirelessly telemetered electrocorticography signals from awake-behaving rats. We hypothesized that such a system could be useful for detecting sporadic but clinically relevant electrophysiological events. In an 18-hour, overnight recording, seizure activity was detected in a pre-clinical rodent model of global ischemic brain injury. We subsequently turned to the design of neurostimulation circuits. Three critical features of neurostimulation devices are safety, programmability, and specificity. We conceived and implemented a neurostimulator architecture that utilizes a compact on-chip circuit for charge balancing (safety), digital-to-analog converter calibration (programmability) and current steering (specificity). Charge balancing accuracy was measured at better than 0.3%, the digital-to-analog converters achieved 8-bit resolution, and physiological effects of current steering stimulation were demonstrated in an anesthetized rat. Lastly, to implement a bidirectional neural interface, both the recording and stimulation circuits were fabricated on a single chip. In doing so, we implemented a low noise, ultra-low power recording front end with a high dynamic range. The recording circuits achieved a signal-to-noise ratio of 58 dB and a spurious-free dynamic range of better than 70 dB, while consuming 5.5 μW per channel. We demonstrated bidirectional operation of the chip by recording cardiac modulation induced through vagus nerve stimulation, and demonstrated closed-loop control of cardiac rhythm

Neutralisation of myoelectric interference from recorded nerve signals using models of the electrode impedance

Any form of paralysis due to spinal cord injury or other medical condition, can have a significant impact on the quality and life expectancy of an individual. Advances in medicine and surgery have offered solutions that can improve the condition of a patient, however, most of the times an individual’s life does not dramatically improve. Implanted neuroprosthetic devices can partially restore the lost functionalities by means of functional electrical stimulation techniques. This involves applying patterns of electrical current pulses to innervate the neural pathways between the brain and the affected muscles/organs, while recording of neural information from peripheral nerves can be used as feedback to improve performance. Recording naturally occurring nerve signals via implanted electrodes attached to tripolar amplifier configurations is an approach that has been successfully used for obtaining desired information in non-acute preparations since the mid-70s. The neural signal (i.e. ENG), which can be exploited as feedback to another system (e.g. a stimulator), or simply extracted for further processing, is then intrinsically more reliable in comparison to signals obtained by artificial sensors. Sadly, neural recording of this type can be greatly compromised by myoelectric (i.e. EMG) interference, which is present at the neural interface and registered by the recording amplifier. Although current amplifier configurations reduce myoelectric interference this is suboptimal and therefore there is room for improvement. The main difficulty exists in the frequency-dependence of the electrode-tissue interface impedance which is complex. The simplistic Quasi-Tripole amplifier configuration does not allow for the complete removal of interference but it is the most power efficient because it uses only one instrumentation amplifier. Conversely, the True-Tripole and its developed automatic counterpart the Adaptive-Tripole, although minimise interference and provide means of compensating for the electrode asymmetries and changes that occur to the neural interface (e.g. due to tissue growth), they do not remove interference completely as the insignificant electrode impedance is still important. Additionally, removing interference apart from being dependent on the frequency of the interfering source, it is also subject to its proximity and orientation with respect to the recording electrodes, as this affects the field. Hence neutralisation with those two configurations, in reality, is not achieved in the entire bandwidth of the neural signal in the interfering spectrum. As both are less power efficient than the Quasi-Tripole an alternative configuration offering better performance in terms of interference neutralisation (i.e. frequency-independent, insensitive to the external interference fields) and, if possible, consume less power, is considered highly attractive. The motivation of this work is based on the following fact: as there are models that can mimic the frequency response of metal electrodes it should be possible, by constructing a network of an equivalent arrangement to the impedance of electrodes, to fit the characteristic neutralisation impedance – the impedance needed to balance a recording tripole – and ideally require no adjustment for removing interference. The validity of this postulation is proven in a series of in-vitro preparations using a modified version of the Quasi-Tripole made out of discrete circuit components where an impedance is placed at either side of the outer electrodes for balancing the recording arrangement. Various models were used in place of that impedance. In particular, representing the neutralisation impedance as a parallel RC reduced interference by a factor of 10 at all frequencies in the bandwidth of the neural signal while removed it completely at a spot frequency. Conversely, modelling the effect of the constant phase angle impedance of highly polarisable electrodes using a 20 stages non-uniform RC ladder network resulted in the minimisation of interference without the initial requirement of continuous adjustment. It is demonstrated that with a model that does not perfectly fit the impedance profile of a monopolar electrochemical cell an average reduction in interference of about 100 times is achieved, with the cell arranged as a Wheatstone bridge that can be balanced in the ENG band

Bladder Volume Decoding from Afferent Neural Activity

RÉSUMÉ Lorsque les fonctions de stockage et de miction de la vessie échouent à la suite de traumatismes médullaires, ou en raison d'autres maladies neurologiques, de conditions de santé ou au vieillissement, des complications graves pour la santé du patient se produisent. Actuellement, il est possible de restaurer partiellement les fonctions de la vessie chez les patients réfractaires aux médicaments à l'aide des neurostimulateurs implantables. Pour améliorer l'efficacité et la sécurité de ces neuroprothèses, il faut un capteur de la vessie capable de détecter l’urine stockée afin de mettre en place un système en boucle fermée qui applique la stimulation électrique uniquement lorsque nécessaire. Le capteur peut également servir à aviser les patients ayant des sensations affaiblies pour les aviser en temps opportun le moment où la vessie doit être vidée ou quand un volume résiduel postmictionnel anormalement élevé reste après une miction incomplète. Dans cette thèse, on présente de nouvelles méthodes de mesure, ainsi qu’un processeur de signal numérique dédié pour décoder en temps réel le volume de la vessie à partir des enregistrements neuronaux afférents provenant des récepteurs naturels présents dans la paroi de la vessie. Nos principales contributions sont rapportées dans trois articles de journaux avec comité de lecture. On présente d'abord une revue exhaustive de la littérature comprenant des articles de journaux, des brevets et les livres les plus réputés portant sur l'anatomie, la physiologie et la physiopathologie du tractus urinaire inférieur ainsi que sur la mesure du volume ou la pression de la vessie. Cette étude nous a permis d'identifier les besoins qu'un capteur de la vessie doit satisfaire pour être utilisé dans des applications chroniques telles que celles proposées dans cette thèse. On présente aussi le résultat d’une analyse exhaustive des caractéristiques anatomiques et physiologiques de la vessie que nous avons identifiées d’avoir exercé une influence, ou même d’avoir empêché, la réalisation d'un tel capteur dans des études faites au cours des dernières années. Sur la base de cette étude et de l'évaluation systématique des méthodes de mesure pour la vessie, on a conclu que le principe de mesure le mieux adapté pour la surveillance chronique du volume de la vessie était la détection, la discrimination et le décodage de l'activité neuronale afférente découlant des récepteurs spécialisés du volume (mécanorécepteurs), au sujet desquels certains auteurs ont émis l'hypothèse de leur existence dans la muqueuse interne de la vessie. Ensuite, on présente la méthode de mesure qui permet d'estimer en temps réel le volume de la vessie à partir de l'activité afférente des mécanorécepteurs. Notre méthode a été validée avec les----------ABSTRACT Failure of the storage and voiding functions of the urinary bladder due to spinal cord injury (SCI), neural diseases, health conditions, or aging, causes serious complications in a patient's health. Currently, it is possible to partially restore bladder functions in drug-refractory patients using implantable neurostimulators. Improving the efficacy and safety of these neuroprostheses used for bladder functions restoration requires a bladder sensor (BS) capable of detecting urine volume in real-time to implement a closed-loop system that applies electrical stimulation only when required. The BS can also trigger an early warning to advise patients with impaired sensations when the bladder should be voided or when an abnormally high post-voiding residual volume remains after an incomplete voiding. In this thesis, we present new measurement methods and a dedicated digital signal processor for real-time decoding of the bladder volume through afferent neural signals arising from natural receptors present in the bladder wall. The main contributions of this thesis have been reported in three peer-reviewed journal papers. We first present a comprehensive literature review, including papers, patents and mainstay books of bladder anatomy, physiology, and pathophysiology. This review allowed us to identify the requirements (user needs) that a BS must meet for chronic applications, such as those proposed in this thesis. An exhaustive analysis of the particular anatomical and physiological characteristics of the bladder, which we realized had influenced or prevented the achievement of a BS for monitoring the bladder volume or pressure in past studies, are also presented. Based on this study and on a systematic assessment of the measurement methods published in past years, we determined the best measurement principle for chronic bladder volume monitoring: the detection, discrimination and decoding of the afferent neural activity stemming from specialized volume receptors (mechanoreceptors), on which some authors had hypothesized about its existence in the bladder inner mucosa. Next, we present methods that allows for a real-time estimation of bladder volume through the afferent activity of the bladder mechanoreceptors. Our method was validated with data acquired from anesthetized rats in acute experiments. It was possible to qualitatively estimate three states of bladder fullness in 100% of trials when the recorded afferent activity exhibited a Spearman’s correlation coefficient of 0.6 or better. Furthermore, we could quantitatively estimate the bladder volume, and also its pressure, using time-windows of properly chosen duration. The mea

Advances in Microelectronics for Implantable Medical Devices

Implantable medical devices provide therapy to treat numerous health conditions as well as monitoring and diagnosis. Over the years, the development of these devices has seen remarkable progress thanks to tremendous advances in microelectronics, electrode technology, packaging and signal processing techniques. Many of today’s implantable devices use wireless technology to supply power and provide communication. There are many challenges when creating an implantable device. Issues such as reliable and fast bidirectional data communication, efficient power delivery to the implantable circuits, low noise and low power for the recording part of the system, and delivery of safe stimulation to avoid tissue and electrode damage are some of the challenges faced by the microelectronics circuit designer. This paper provides a review of advances in microelectronics over the last decade or so for implantable medical devices and systems. The focus is on neural recording and stimulation circuits suitable for fabrication in modern silicon process technologies and biotelemetry methods for power and data transfer, with particular emphasis on methods employing radio frequency inductive coupling. The paper concludes by highlighting some of the issues that will drive future research in the field

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

Integrated Circuits and Systems for Smart Sensory Applications

Connected intelligent sensing reshapes our society by empowering people with increasing new ways of mutual interactions. As integration technologies keep their scaling roadmap, the horizon of sensory applications is rapidly widening, thanks to myriad light-weight low-power or, in same cases even self-powered, smart devices with high-connectivity capabilities. CMOS integrated circuits technology is the best candidate to supply the required smartness and to pioneer these emerging sensory systems. As a result, new challenges are arising around the design of these integrated circuits and systems for sensory applications in terms of low-power edge computing, power management strategies, low-range wireless communications, integration with sensing devices. In this Special Issue recent advances in application-specific integrated circuits (ASIC) and systems for smart sensory applications in the following five emerging topics: (I) dedicated short-range communications transceivers; (II) digital smart sensors, (III) implantable neural interfaces, (IV) Power Management Strategies in wireless sensor nodes and (V) neuromorphic hardware

An Implantable Stimulator for Selective Stimulation of Nerves

Acute experimentation performed at many centres over the last twenty years has shown techniques which allow small neurones to be stimulated without large, the reverse of the normal recruitment order usually encountered during electrical stimulation; one-way excitation of neurones; and excitation of only a region of a nerve. These techniques should improve neural prosthesis by, for example: avoiding pain during stimulation and requiring electrode sites and therefore fewer incisions. To enable chronic clinical experiments of these advanced methods, there is a need for a specialised chronically-implantable stimulator, which can control either dipolar, tripolar or pentapolar nerve cuff electrodes. This thesis is concerned with the design and development of such a stimulator and, in particular, a fully customised analogue integrated circuit that converts incoming digital words into corresponding stimulation currents. A binary word is transmitted to the implant, which defines the current waveform parameters for the electrodes. This word is loaded into a shift register at the input. Part of the word is presented to a digital to analogue converter, to specify stimulation amplitude, and a pulse generator, which generates either a quasi-trapezoidal, or a square shaped stimulation waveforms. Four novel low offset linear transconductors provide the stimulation currents that are switched to the desired outputs. The charge balancing of the stimulation waveform is realised by a very long time-constant switched capacitor integrator. The major difficulties in the design of the analogue full custom IC proved to be the linear transconductor stages and the integrator. Results for the test ICs are presented and the design of a complete stimulator system is described