Ultra-Miniaturised CMOS Current Driver for Wireless Biphasic Intracortical Microstimulation

This work shows an ultra-miniaturised and ultralow-power CMOS current driver for biphasic intracortical microstimulation. The CMOS driver is composed of a leakage-based voltage-to-current converter and an H-bridge circuit providing biphasic charge-balanced current stimulation. The circuit has been simulated, fabricated and tested. The current driver consumes 1.87 µW with a supply voltage of 1.8 V, and it occupies a silicon area of 15×12.4 µm 2 . The driver works in linearity in the current range between 23−92 µ

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

ASIC para estimulação elétrica da espinal medula

Spinal Cord Injuries (SCI) have severe consequences such as tetraplegia and paraplegia, which dramatically affect the healthcare of the patients. Successful therapies for such injuries are yet to be attainable. Currently, there is a focus on the study and implementation of small implantable devices that are capable of providing in-vivo electrical stimulation to the spinal cord. Since the impedance of the neural tissue experiences constant changes, the focus is on using current stimulation instead of voltage, to compensate the impedance variations. Furthermore, the usage of scaffolds to provide alignment on the regrown fibers, combined with electrical stimulation is viewed as possible solution for SCI therapy. The NeuroStim- Spinal project, in which this work is inserted, aims to propose a SCI therapy based on in-vivo electrical stimulation combined with 3D printed scaffolds that have in its composition based materials (GBM) and adipose derived decellularized tissue (adECM). The work presented is an application-specific integrated circuit design (ASIC) that provides current-mode stimulation for neuronal regeneration, with the objective of providing in-vivo electrical stimulation for SCI therapy. The main challenges on the design of such devices is in obtaining low circuit area and power consumption, while maintaining the specifications needed. These characteristics are important, since it is intended to be an implantable device. The stimulation circuit consists of, a communication interface with a microcontroller using the Serial Peripheral Communication (SPI) protocol, a 10-bit DAC (Digital-to-Analog Converter) based on a binary charge scaling architecture, a voltage-to-current converter with a feed-forward voltage attenuator (FFVA) architecture, and a H-bridge circuit composed of CMOS switches to drive the scaffold. Results demonstrate that the system developed is capable of driving current from 0 to 200μA with an absolute error bellow 0.75μA. In addition, the developed circuit can provide these range of currents with high linearity to a 15k load impedance. The system can still provide linear stimulation for higher load impedance’s, but in smaller current ranges. Furthermore, the circuit uses a supply voltage of 5V and has an average power dissipation of 19.5mW. The ASIC was developed using a 0.35μm CMOS technology, has dimensions of 270μm per 700μm, which corresponds to a total area of 0.19mm2. The work was developed using the Cadence software.Lesões na Medula Espinhal são causadas sobretudo devido acidentes rodoviários, quedas e lesões na prática de desportos. Estas têm graves consequências no estado de saúde dos pacientes, uma vez que saõ responsáveis por diagnósticos como tetraplegia e paraplegia. Até hoje, terapias eficazes para este tipo de lesões ainda não foram conseguidas, o que torna esta temática num foco de estudo. Atualmente, uma das orientações deste foco de estudo está direcionado em dispositivos elétricos implantáveis capazes de estimular a espinal medula in-vivo, promovendo a regeneração da mesma. Adicionalmente, o uso de materiais (scaffolds) que permitem manter o alinhemento no crescimento das fibras, em conjunto com estimulação elétrica é vista como a solução consensual para terapias relacionadas com Lesões na Medula Espinhal. Assim, o projeto NeuroStimSpinal, na qual este trabalho se insere, foi proposto. Este tem como objetivo propor uma terapia para esta problemática usando estimulação elétrica em conjunto com scaffolds impressas em 3D. O trabalho apresentado nesta dissertação é baseado num circuito integrado de aplicação específica (CIAE) para estimulação em corrente da espinal medula, com o intuito de promover a regeneração da mesma. Os desafios na implementação deste tipo de circuitos estão relacionados com a necessidade destes terem de ser pequenos em tamanho e consumir uma potência reduzida, mantendo as características necessárias para a estimulação, uma vez que é necessário que o mesmo faça parte de um dispositivo implantável. O circuito de estimulação proposto consiste: numa interface de comunicação com a unidade de controlo (microcontrolador) usando o protocolo Serial Peripheral Communication (SPI); um conversor digital para analógico de 10 bits, o qual se baseia numa arquitetura de escalonamento binário por carga; um conversor tensão para corrente rail-to-rail e uma ponte H que direciona a corrente pela scaffold, cuja implementação se baseia no uso de portas de transmissão como comutadores. Resultados ao trabalho desenvolvido mostram que o circuito é capaz de estimular a scaffold com correntes entre 0 to 200μA com um erro na corrente de estimulação inferior a 0.75μA. O circuito é capaz ainda de fornecer uma corrente linear, na gama mencionada, a cargas com impedancias até 15k . Para cargas superiores o circuito é capaz de fornecer uma corrente linear, embora em gamas de correntes menores. O circuito implementado usa como tensão de alimentação 5V, tem um consumo médio de potência de 19.5mW e ocupa uma área de 0.19mm2. No decurso do trabalho desenvolvido foi utilizada uma tecnlogoia CMOS de 0.35um. A implementação e resultados foram obtidos com recurso ao software Cadence.Mestrado em Engenharia Eletrónica e Telecomunicaçõe

A Closed-Loop Bidirectional Brain-Machine Interface System For Freely Behaving Animals

A brain-machine interface (BMI) creates an artificial pathway between the brain and the external world. The research and applications of BMI have received enormous attention among the scientific community as well as the public in the past decade. However, most research of BMI relies on experiments with tethered or sedated animals, using rack-mount equipment, which significantly restricts the experimental methods and paradigms. Moreover, most research to date has focused on neural signal recording or decoding in an open-loop method. Although the use of a closed-loop, wireless BMI is critical to the success of an extensive range of neuroscience research, it is an approach yet to be widely used, with the electronics design being one of the major bottlenecks. The key goal of this research is to address the design challenges of a closed-loop, bidirectional BMI by providing innovative solutions from the neuron-electronics interface up to the system level. Circuit design innovations have been proposed in the neural recording front-end, the neural feature extraction module, and the neural stimulator. Practical design issues of the bidirectional neural interface, the closed-loop controller and the overall system integration have been carefully studied and discussed.To the best of our knowledge, this work presents the first reported portable system to provide all required hardware for a closed-loop sensorimotor neural interface, the first wireless sensory encoding experiment conducted in freely swimming animals, and the first bidirectional study of the hippocampal field potentials in freely behaving animals from sedation to sleep. This thesis gives a comprehensive survey of bidirectional BMI designs, reviews the key design trade-offs in neural recorders and stimulators, and summarizes neural features and mechanisms for a successful closed-loop operation. The circuit and system design details are presented with bench testing and animal experimental results. The methods, circuit techniques, system topology, and experimental paradigms proposed in this work can be used in a wide range of relevant neurophysiology research and neuroprosthetic development, especially in experiments using freely behaving animals

Bidirectional Propulsion of Devices Along the Gastrointestinal Tract Using Electrostimulation

This thesis describes a method for propelling devices such as video capsule endoscopes in either direction along the small intestines using electrostimulation-induced muscular contractions. When swallowed, passive diagnostic ‘one-shot’ devices rely on sporadic peristaltic movement, possibly missing vital ‘areas of interest’. This bidirectional propulsion method provides active control for that all-important ‘second look’. Design considerations, within the dimensional constraints, required a device shape that would achieve maximum propulsion from safely induced useful contractions produced by the electrodes and encapsulated miniature electrostimulator. Construction materials would have to produce minimal friction against the mucosal surface while having the physical properties to facilitate construction and electrode attachment. Design investigations included coefficient of friction measurements of different construction materials and the evaluation of different capsule and electrode dimensions over a range of stimulation parameters, to obtain optimal propulsion. A swallowable 11 mm diameter device was propelled at 121 mm/min with stimulation parameters of 12.5 Hz, 20 ms, at 20 V in an anaesthetised pig. A modified passive video capsule endoscope was propelled at 120 mm/min with stimulation parameters of 12.5 Hz, 20 ms, at 10 V in an unanaesthetised human volunteer. A radio-controlled capsule incorporating an electrostimulator, voltage converter and 3 V power supply was propelled at 60 mm/min with stimulation parameters of 12.5 Hz, 20 ms, and 30 V in an anaesthetised pig. 4 Other possible uses of electrostimulation were investigated including propulsion of anally administered large intestine devices and introduction of the intestinal mucosal surface into a biopsy chamber. Results are presented. The ultimate aim of the project was to provide bidirectional propulsion for wireless remote controlled devices along the gastrointestinal tract utilising contractile force produced by electrostimulation of the intestinal wall. The controllability of this system could provide clinicians with a real time view of the entire small intestines without surgical enteroscopy

Engineering cytocompatible conducting polymers for bio-related energy applications

Portable, wearable and implantable medical devices (IMDs) can be used to solve various clinical problems such as monitoring of chronic diseases or artificial organ transplantation. Current available IMDs are generally powered by an energy source with a strong case for absolute encapsulation. It would be ideal to minimise the size and volume of the power source for users’ comfort by removing the strong case if the employed materials and by-products are safe for the body. In this thesis, two types of cytocompatible conducting polymers have been fabricated via facial chemical synthesis methods for use in bio-related energy sources that are capable of providing energy with the use of simulated body fluids. They are polypyrrole/poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PPy/PEDOT) hydrogel and asymmetric polypyrrole (PPy) membrane. The demonstrated bio-related energy systems include a bioelectric battery and an energy harvesting system

A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY

This thesis highlights the current gold-standard surgical procedures for the rehabilitation of mimicry in individuals with facial paralysis and explores the potential application of functional electrical stimulation (FES) as a novel treatment restoring the face mimicry. Closed-loop facial pacing represents an innovative solution for prosthetically assisted movements. In particular, blinking is typically symmetrical, enabling healthy eye blink on one side of the face to serve as a trigger to pace assisted blinks on the contralateral side, in case of unilateral peripheral facial palsy. The goals of this research are developing an eyeblink detection system and advancing the understanding of performing surface FES of the facial nerve in order to elicit artificial eyeblinks. The application of a biomimetic device to individuals with acute reversible facial palsy would provide immediate restoration of the periocular function and could be used until either the patient recovers sufficient function to no longer require assistance for eye closure, or the decision is made to proceed with further surgery

Les systèmes monoaminergiques : implication dans la physiopathologie et la thérapie de la maladie de Parkinson

Parkinson’s disease is characterized by the manifestation of motor symptoms mostlyassociated with the degeneration of dopaminergic neurons. While Parkinson’s disease is oftenfocused on motor deficits, the disease is also characterized by non-motor deficits, includinganxiety and depression, which are under studied and consequently are not well treated.Whereas some clinical studies suggested that anxiety and depression could be linked to thedegeneration of dopaminergic neurons, others suggested the involvement of norepinephrineand serotonin in the observed symptoms and also in the efficacy of Levodopa and deep brainstimulation of the subthalamic nucleus.In a first time, we investigated the respective role of the neuronal degeneration of dopamine,noradrenaline and serotonin in the manifestation of motor and non-motor parkinsonian-likedisorders in the rat. Our results demonstrate that despite the importance of the dopaminergicsystem, the disturbances in the three-monoaminergic systems play a key role in themanifestation of motor and non-motor deficits.In a second time, we studied the impact of monoamine depletions on the efficacy ofantiparkinsonian treatments, the Levodopa and deep brain stimulation of the subthalamicnucleus. Our results showed that the combined depletions could deteriorate the efficacy of theLevodopa and of the deep brain stimulation on some deficits. Together, these results canexplain the lack of efficacy of the antiparkinsonian treatments in some patients and thedifficulty to treat all the symptoms.Finally, we investigated the link between the subthalamic nucleus, which is an excitatorystructure of the basal ganglia, and the motor deficits, as well as the involvement of thebasolateral amygdala and the lateral habenula in emotional control of the behavior, and nonmotordeficits. We showed the parallel between changes in the neuronal activity of thesubthalamic nucleus and the motor deficits, of the basolateral amygdala and anxiety and ofthe lateral habenula and depression.Results from this thesis provide new evidences on the involvement of the threemonoaminergicsystems in the pathophysiology and the therapy of Parkinson’s disease.La maladie de Parkinson est caractérisée par la manifestation de symptômes moteursprincipalement dus à la dégénérescence du système dopaminergique. Malgré l'accent mis surles déficits moteurs, la maladie de Parkinson est également caractérisée par des symptômesnon moteurs, incluant l'anxiété et la dépression, qui sont sous-étudiés et de ce fait pas bientraités. Alors que certaines études cliniques ont suggéré que l'anxiété et la dépressionpourraient être associées à la dégénérescence des neurones dopaminergiques, d'autres ontsuggéré l'implication de la dégénérescence des neurones noradrénergiques etsérotoninergiques dans les troubles observés mais également dans les effets induits par laLévodopa et la stimulation cérébrale profonde du noyau sous-thalamique.Dans un premier temps, nous avons étudié le rôle respectif de la dopamine, de lanoradrénaline et de la sérotonine dans la manifestation des déficits parkinsoniens moteurs etnon moteurs chez le rat. L’ensemble de nos résultats démontre que malgré l’importance dusystème dopaminergique, la perturbation des trois systèmes monoaminergiques joue un rôleimportant à la fois dans la manifestation des troubles moteurs et non moteurs.Nous avons également étudier l’impact des monoamines sur l’efficacité des traitementsantiparkinsoniens, à savoir, la Lévodopa et la stimulation cérébrale profonde du noyau sousthalamique,sur les troubles observés. Nos résultats montrent que la déplétion combinée dessystèmes monoaminergiques peut altérer l’efficacité de la Lévodopa ainsi que de lastimulation cérébrale profonde sur certains troubles. Ces résultats peuvent expliquer lemanque d’efficacité des traitements antiparkinsoniens chez certains patients et la difficulté àtraiter tous les symptômes.Pour finir, nous avons voulu mettre en évidence le lien entre le noyau sous-thalamique,structure excitatrice des ganglions de la base et les troubles moteurs, ainsi que l’amygdalebasolatérale et l’habénula latérale, structures impliquées dans les comportements émotionnels,et les troubles non moteurs. Nous avons mis en évidence le parallèle existant entre lesmodifications du mode de décharge des neurones du NST et les troubles moteurs, leschangements de l’amygdale basolatérale et les troubles anxieux ainsi que ceux de l’habénulalatérale et les troubles dépressifs.Les résultats de ces travaux de thèse ont donc permis d’apporter de nouvelles évidences surl’implication des trois systèmes monoaminergiques dans la physiopathologie et la thérapie dela maladie de Parkinson