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

Conformable transistors for bioelectronics

The diversity of network disruptions that occur in patients with neuropsychiatric disorders creates a strong demand for personalized medicine. Such approaches often take the form of implantable bioelectronic devices that are capable of monitoring pathophysiological activity for identifying biomarkers to allow for local and responsive delivery of intervention. They are also required to transmit this data outside of the body for evaluation of the treatment’s efficacy. However, the ability to perform these demanding electronic functions in the complex physiological environment with minimum disruption to the biological tissue remains a big challenge. An optimal fully implantable bioelectronic device would require each component from the front-end to the data transmission to be conformable and biocompatible. For this reason, organic material-based conformable electronics are ideal candidates for components of bioelectronic circuits due to their inherent flexibility, and soft nature. In this work, first an organic mixed-conducting particulate composite material (MCP) able to form functional electronic components and non-invasively acquire high–spatiotemporal resolution electrophysiological signals by directly interfacing human skin is presented. Secondly, we introduce organic electrochemical internal ion-gated transistors (IGTs) as a high-density, high-amplification sensing component as well as a low leakage, high-speed processing unit. Finally, a novel wireless, battery-free strategy for electrophysiological signal acquisition, processing, and transmission that employs IGTs and an ionic communication circuit (IC) is introduced. We show that the wirelessly-powered IGTs are able to acquire and modulate neurophysiological data in-vivo and transmit them transdermally, eliminating the need for any hard Si-based electronics in the implant

Neurosciences and Wireless Networks: The Potential of Brain-Type Communications and Their Applications

This paper presents the first comprehensive tutorial on a promising research field located at the frontier of two well-established domains, neurosciences and wireless communications, motivated by the ongoing efforts to define the Sixth Generation of Mobile Networks (6G). In particular, this tutorial first provides a novel integrative approach that bridges the gap between these two seemingly disparate fields. Then, we present the state-of-the-art and key challenges of these two topics. In particular, we propose a novel systematization that divides the contributions into two groups, one focused on what neurosciences will offer to future wireless technologies in terms of new applications and systems architecture (Neurosciences for Wireless Networks), and the other on how wireless communication theory and next-generation wireless systems can provide new ways to study the brain (Wireless Networks for Neurosciences). For the first group, we explain concretely how current scientific understanding of the brain would enable new applications within the context of a new type of service that we dub brain-type communications and that has more stringent requirements than human- and machine-type communication. In this regard, we expose the key requirements of brain-type communication services and discuss how future wireless networks can be equipped to deal with such services. Meanwhile, for the second group, we thoroughly explore modern communication systems paradigms, including Internet of Bio-Nano Things and wireless-integrated brain-machine interfaces, in addition to highlighting how complex systems tools can help bridging the upcoming advances of wireless technologies and applications of neurosciences. Brain-controlled vehicles are then presented as our case study to demonstrate for both groups the potential created by the convergence of neurosciences and wireless communications, probably in 6G. In summary, this tutorial is expected to provide a largely missing articulation between neurosciences and wireless communications while delineating concrete ways to move forward in such an interdisciplinary endeavor

Radio Frequency Antenna Designs and Methodologies for Human Brain Computer Interface and Ultrahigh Field Magnetic Resonance Imaging

Brain Computer Interface (BCI) and Magnetic Resonance Imaging (MRI) are two powerful medical diagnostic techniques used for human brain studies. However, wired power connection is a huge impediment for the clinical application of BCI, and most current BCIs have only been designed for immobile users in a carefully controlled environment. For the ultrahigh field (≥7T) MRI, limitations such as inhomogeneous distribution of the transmit field (B1+) and potential high power deposition inside the human tissues have not yet been fully combated by existing methods and are central in making ultrahigh field MRI practical for clinical use. In this dissertation, radio frequency (RF) methods are applied and RF antennas/coils are designed and optimized in order to overcome these barriers. These methods include: 1) designing implanted miniature antennas to transmit power wirelessly for implanted BCIs; 2) optimizing a new 20-channel transmit array design for 7 Tesla MRI neuroimaging applications; and 3) developing and implementing a dual-optimization method to design the RF shielding for fast MRI imaging methods. First, three miniaturized implanted antennas are designed and results obtained using finite difference time domain (FDTD) simulations demonstrate that a maximum RF power of up to 1.8 miliwatts can be received at 2 GHz when the antennas are implanted at the dura, without violating the government safety regulations. Second, Eigenmode arrangement of the 20-channel transmit coil allows control of RF excitation not only at the XY plane but also along the Z direction. The presented results show the optimized eigenmode could generate 3D uniform transmit B1+ excitations. The optimization results have been verified by in-vivo experiments, and they are applied with different protocol sequences on a Siemens 7 Tesla MRI human whole body scanner equipped with 8 parallel transmit channels. Third, echo planar imaging (EPI), B1+ maps and S matrix measurements are used to verify that the proposed RF shielding can suppress the eddy currents while maintaining the RF characteristics of the transmit coil. The contributions presented here will provide a long-term and safer power transmission path compared to the wire-connected implanted BCIs and will bring ultrahigh field MRI technology closer to clinical applications

Analog Front-End Circuits for Massive Parallel 3-D Neural Microsystems.

Understanding dynamics of the brain has tremendously improved due to the progress in neural recording techniques over the past five decades. The number of simultaneously recorded channels has actually doubled every 7 years, which implies that a recording system with a few thousand channels should be available in the next two decades. Nonetheless, a leap in the number of simultaneous channels has remained an unmet need due to many limitations, especially in the front-end recording integrated circuits (IC). This research has focused on increasing the number of simultaneously recorded channels and providing modular design approaches to improve the integration and expansion of 3-D recording microsystems. Three analog front-ends (AFE) have been developed using extremely low-power and small-area circuit techniques on both the circuit and system levels. The three prototypes have investigated some critical circuit challenges in power, area, interface, and modularity. The first AFE (16-channels) has optimized energy efficiency using techniques such as moderate inversion, minimized asynchronous interface for data acquisition, power-scalable sampling operation, and a wide configuration range of gain and bandwidth. Circuits in this part were designed in a 0.25μm CMOS process using a 0.9-V single supply and feature a power consumption of 4μW/channel and an energy-area efficiency of 7.51x10^15 in units of J^-1Vrms^-1mm^-2. The second AFE (128-channels) provides the next level of scaling using dc-coupled analog compression techniques to reject the electrode offset and reduce the implementation area further. Signal processing techniques were also explored to transfer some computational power outside the brain. Circuits in this part were designed in a 180nm CMOS process using a 0.5-V single supply and feature a power consumption of 2.5μW/channel, and energy-area efficiency of 30.2x10^15 J^-1Vrms^-1mm^-2. The last AFE (128-channels) shows another leap in neural recording using monolithic integration of recording circuits on the shanks of neural probes. Monolithic integration may be the most effective approach to allow simultaneous recording of more than 1,024 channels. The probe and circuits in this part were designed in a 150 nm SOI CMOS process using a 0.5-V single supply and feature a power consumption of only 1.4μW/channel and energy-area efficiency of 36.4x10^15 J^-1Vrms^-1mm^-2.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98070/1/ashmouny_1.pd

Régulateurs "Waterfall" : une nouvelle topologie énergétique pour l'électronique

Ce travail décrit une nouvelle topologie d'alimentation qui apporte des bénéfices aux dispositifs portables et aux composants électroniques à faible consommation. À l'autre extrémité du spectre, il serait également applicable aux systèmes à tension de bus plus élevée, tels que les panneaux solaires et les véhicules électriques, qui doivent décomposer des tensions plus élevées en domaines utilisables. La nouvelle topologie, que nous avons nommée Waterfall regulator, est décrite dans le présent travail et nommée ainsi pour ses caractéristiques saillantes rappelant une chute en cascade. Ce dispositif ouvre de nouvelles perspectives pour les systèmes à très basse consommation, basse tension et courant faible. Le mode de fonctionnement consiste à diviser une source d'alimentation brute en plusieurs domaines de tension, qui peuvent ensuite être utilisés pour alimenter les éléments individuels d'un système ou plusieurs unités indépendantes. Nous décrivons ici le premier rapport sur la réussite de la version de recyclage de l'énergie de ce nouveau système. Le dispositif se caractérise par une série de régulateurs de tension à faible chute et de circuits de déversement de courant (pass MOSFET). Le régulateur partage le courant qui traverse sa charge respective et complète le courant du stade suivant par un déversoir de courant, selon les besoins. Le contrôle s'effectue via une architecture de contrôle en cascade et peut être étendu à des périphériques d'ordre supérieur.This work described a new power supply topology that benefits portable device and low power electronics. At the other end of the spectrum, it is also applicable to higher bus voltage systems like solar panels and electric vehicles that must split higher voltages into usable domains. The new topology, which we named waterfall regulator, is describe herein and named as such for its salient features reminiscent of a waterfall. It opens up a new realm of possibilities for supra low power, low voltage and low current systems. The mode of operation consists of splitting a raw supply source into smaller voltage domains which can then be used for powering individual element of a system or powering multiple independent units. We describe here the first report of successful energy recycling version of this novel system. The devices are composed of a series of low dropout voltage regulators and current spillways circuits (pass MOSFET). The regulators share current passing thought their respective load and supplement current through a current spillway as required. Control is achieved through a cascade architecture and can be scaled up to higher order devices

Development of Advanced Closed-Loop Brain Electrophysiology Systems for Freely Behaving Rodents

[ES] La electrofisiología extracelular es una técnica ampliamente usada en investigación neurocientífica, la cual estudia el funcionamiento del cerebro mediante la medición de campos eléctricos generados por la actividad neuronal. Esto se realiza a través de electrodos implantados en el cerebro y conectados a dispositivos electrónicos para amplificación y digitalización de las señales. De los muchos modelos animales usados en experimentación, las ratas y los ratones se encuentran entre las especies más comúnmente utilizadas. Actualmente, la experimentación electrofisiológica busca condiciones cada vez más complejas, limitadas por la tecnología de los dispositivos de adquisición. Dos aspectos son de particular interés: Realimentación de lazo cerrado y comportamiento en condiciones naturales. En esta tesis se presentan desarrollos con el objetivo de mejorar diferentes facetas de estos dos problemas. La realimentación en lazo cerrado se refiere a todas las técnicas en las que los estímulos son producidos en respuesta a un evento generado por el animal. La latencia debe ajustarse a las escalas temporales bajo estudio. Los sistemas modernos de adquisición presentan latencias en el orden de los 10ms. Sin embargo, para responder a eventos rápidos, como pueden ser los potenciales de acción, se requieren latencias por debajo de 1ms. Además, los algoritmos para detectar los eventos o generar los estímulos pueden ser complejos, integrando varias entradas de datos en tiempo real. Integrar el desarrollo de dichos algoritmos en las herramientas de adquisición forma parte del diseño experimental. Para estudiar comportamientos naturales, los animales deben ser capaces de moverse libremente en entornos emulando condiciones naturales. Experimentos de este tipo se ven dificultados por la naturaleza cableada de los sistemas de adquisición. Otras restricciones físicas, como el peso de los implantes o limitaciones en el consumo de energía, pueden también afectar a la duración de los experimentos, limitándola. La experimentación puede verse enriquecida cuando los datos electrofisiológicos se ven complementados con múltiples fuentes distintas. Por ejemplo, seguimiento de los animales o miscroscopía. Herramientas capaces de integrar datos independientemente de su origen abren la puerta a nuevas posibilidades. Los avances tecnológicos presentados abordan estas limitaciones. Se han diseñado dispositivos con latencias de lazo cerrado inferiores a 200us que permiten combinar cientos de canales electrofisiológicos con otras fuentes de datos, como vídeo o seguimiento. El software de control para estos dispositivos se ha diseñado manteniendo la flexibilidad como objetivo. Se han desarrollado interfaces y estándares de naturaleza abierta para incentivar el desarrollo de herramientas compatibles entre ellas. Para resolver los problemas de cableado se siguieron dos métodos distintos. Uno fue el desarrollo de headstages ligeros combinados con cables coaxiales ultra finos y conmutadores activos, gracias al seguimiento de animales. Este desarrollo permite reducir el esfuerzo impuesto a los animales, permitiendo espacios amplios y experimentos de larga duración, al tiempo que permite el uso de headstages con características avanzadas. Paralelamente se desarrolló un tipo diferente de headstage, con tecnología inalámbrica. Se creó un algoritmo de compresión digital especializado capaz de reducir el ancho de banda a menos del 65% de su tamaño original, ahorrando energía. Esta reducción permite baterías más ligeras y mayores tiempos de operación. El algoritmo fue diseñado para ser capaz de ser implementado en una gran variedad de dispositivos. Los desarrollos presentados abren la puerta a nuevas posibilidades experimentales para la neurociencia, combinando adquisición elextrofisiológica con estudios conductuales en condiciones naturales y estímulos complejos en tiempo real.[CA] L'electrofisiologia extracel·lular és una tècnica àmpliament utilitzada en la investigació neurocientífica, la qual permet estudiar el funcionament del cervell mitjançant el mesurament de camps elèctrics generats per l'activitat neuronal. Això es realitza a través d'elèctrodes implantats al cervell, connectats a dispositius electrònics per a l'amplificació i digitalització dels senyals. Dels molts models animals utilitzats en experimentació electrofisiològica, les rates i els ratolins es troben entre les espècies més utilitzades. Actualment, l'experimentació electrofisiològica busca condicions cada vegada més complexes, limitades per la tecnologia dels dispositius d'adquisició. Dos aspectes són d'especial interès: La realimentació de sistemes de llaç tancat i el comportament en condicions naturals. En aquesta tesi es presenten desenvolupaments amb l'objectiu de millorar diferents aspectes d'aquestos dos problemes. La realimentació de sistemes de llaç tancat es refereix a totes aquestes tècniques on els estímuls es produeixen en resposta a un esdeveniment generat per l'animal. La latència ha d'ajustar-se a les escales temporals sota estudi. Els sistemes moderns d'adquisició presenten latències en l'ordre dels 10ms. No obstant això, per a respondre a esdeveniments ràpids, com poden ser els potencials d'acció, es requereixen latències per davall de 1ms. A més a més, els algoritmes per a detectar els esdeveniments o generar els estímuls poden ser complexos, integrant varies entrades de dades a temps real. Integrar el desenvolupament d'aquests algoritmes en les eines d'adquisició forma part del disseny dels experiments. Per a estudiar comportaments naturals, els animals han de ser capaços de moure's lliurement en ambients emulant condicions naturals. Aquestos experiments es veuen limitats per la natura cablejada dels sistemes d'adquisició. Altres restriccions físiques, com el pes dels implants o el consum d'energia, poden també limitar la duració dels experiments. L'experimentació es pot enriquir quan les dades electrofisiològiques es complementen amb dades de múltiples fonts. Per exemple, el seguiment d'animals o microscòpia. Eines capaces d'integrar dades independentment del seu origen obrin la porta a noves possibilitats. Els avanços tecnològics presentats tracten aquestes limitacions. S'han dissenyat dispositius amb latències de llaç tancat inferiors a 200us que permeten combinar centenars de canals electrofisiològics amb altres fonts de dades, com vídeo o seguiment. El software de control per a aquests dispositius s'ha dissenyat mantenint la flexibilitat com a objectiu. S'han desenvolupat interfícies i estàndards de naturalesa oberta per a incentivar el desenvolupament d'eines compatibles entre elles. Per a resoldre els problemes de cablejat es van seguir dos mètodes diferents. Un va ser el desenvolupament de headstages lleugers combinats amb cables coaxials ultra fins i commutadors actius, gràcies al seguiment d'animals. Aquest desenvolupament permet reduir al mínim l'esforç imposat als animals, permetent espais amplis i experiments de llarga durada, al mateix temps que permet l'ús de headstages amb característiques avançades. Paral·lelament es va desenvolupar un tipus diferent de headstage, amb tecnologia sense fil. Es va crear un algorisme de compressió digital especialitzat capaç de reduir l'amplada de banda a menys del 65% de la seua grandària original, estalviant energia. Aquesta reducció permet bateries més lleugeres i majors temps d'operació. L'algorisme va ser dissenyat per a ser capaç de ser implementat a una gran varietat de dispositius. Els desenvolupaments presentats obrin la porta a noves possibilitats experimentals per a la neurociència, combinant l'adquisició electrofisiològica amb estudis conductuals en condicions naturals i estímuls complexos en temps real.[EN] Extracellular electrophysiology is a technique widely used in neuroscience research. It can offer insights on how the brain works by measuring the electrical fields generated by neural activity. This is done through electrodes implanted in the brain and connected to amplification and digitization electronic circuitry. Of the many animal models used in electrophysiology experimentation, rodents such as rats and mice are among the most popular species. Modern electrophysiology experiments seek increasingly complex conditions that are limited by acquisition hardware technology. Two particular aspects are of special interest: Closed-loop feedback and naturalistic behavior. In this thesis, we present developments aiming to improve on different facets of these two problems. Closed-loop feedback encompasses all techniques in which stimuli is produced in response of an event generated by the animal. Latency, the time between trigger event and stimuli generation, must adjust to the biological timescale being studied. While modern acquisition systems feature latencies in the order of 10ms, response to fast events such as high-frequency electrical transients created by neuronal activity require latencies under $1ms$. In addition, algorithms for triggering or generating closed-loop stimuli can be complex, integrating multiple inputs in real-time. Integration of algorithm development into acquisition tools becomes an important part of experiment design. For electrophysiology experiments featuring naturalistic behavior, animals must be able to move freely in ecologically meaningful environments, mimicking natural conditions. Experiments featuring elements such as large arenaa, environmental objects or the presence of another animals are, however, hindered by the wired nature of acquisition systems. Other physical constraints, such as implant weight or power restrictions can also affect experiment time, limiting their duration. Beyond the technical limits, complex experiments are enriched when electrophysiology data is integrated with multiple sources, for example animal tracking or brain microscopy. Tools allowing mixing data independently of the source open new experimental possibilities. The technological advances presented on this thesis addresses these topics. We have designed devices with closed-loop latencies under 200us while featuring high-bandwidth interfaces. These allow the simultaneous acquisition of hundreds of electrophysiological channels combined with other heterogeneous data sources, such as video or tracking. The control software for these devices was designed with flexibility in mind, allowing easy implementation of closed-loop algorithms. Open interface standards were created to encourage the development of interoperable tools for experimental data integration. To solve wiring issues in behavioral experiments, we followed two different approaches. One was the design of light headstages, coupled with ultra-thin coaxial cables and active commutator technology, making use of animal tracking. This allowed to reduce animal strain to a minimum allowing large arenas and prolonged experiments with advanced headstages. A different, wireless headstage was also developed. We created a digital compression algorithm specialized for neural electrophysiological signals able to reduce data bandwidth to less than 65.5% its original size without introducing distortions. Bandwidth has a large effect on power requirements. Thus, this reduction allows for lighter batteries and extended operational time. The algorithm is designed to be able to be implemented in a wide variety of devices, requiring low hardware resources and adding negligible power requirements to a system. Combined, the developments we present open new possibilities for neuroscience experiments combining electrophysiology acquisition with natural behaviors and complex, real-time, stimuli.The research described in this thesis was carried out at the Polytechnic University of Valencia (Universitat Politècnica de València), Valencia, Spain in an extremely close collaboration with the Neuroscience Institute - Spanish National Research Council - Miguel Hernández University (Instituto de Neurociencias - Consejo Superior de Investigaciones Cientí cas - Universidad Miguel Hernández), San Juan de Alicante, Spain. The projects described in chapters 3 and 4 were developed in collabo- ration with, and funded by, Open Ephys, Cambridge, MA, USA and OEPS - Eléctronica e produção, unipessoal lda, Algés, Portugal.Cuevas López, A. (2021). Development of Advanced Closed-Loop Brain Electrophysiology Systems for Freely Behaving Rodents [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/179718TESI