Studies in RF power communication, SAR, and temperature elevation in wireless implantable neural interfaces

Implantable neural interfaces are designed to provide a high spatial and temporal precision control signal implementing high degree of freedom real-time prosthetic systems. The development of a Radio Frequency (RF) wireless neural interface has the potential to expand the number of applications as well as extend the robustness and longevity compared to wired neural interfaces. However, it is well known that RF signal is absorbed by the body and can result in tissue heating. In this work, numerical studies with analytical validations are performed to provide an assessment of power, heating and specific absorption rate (SAR) associated with the wireless RF transmitting within the human head. The receiving antenna on the neural interface is designed with different geometries and modeled at a range of implanted depths within the brain in order to estimate the maximum receiving power without violating SAR and tissue temperature elevation safety regulations. Based on the size of the designed antenna, sets of frequencies between 1 GHz to 4 GHz have been investigated. As expected the simulations demonstrate that longer receiving antennas (dipole) and lower working frequencies result in greater power availability prior to violating SAR regulations. For a 15 mm dipole antenna operating at 1.24 GHz on the surface of the brain, 730 uW of power could be harvested at the Federal Communications Commission (FCC) SAR violation limit. At approximately 5 cm inside the head, this same antenna would receive 190 uW of power prior to violating SAR regulations. Finally, the 3-D bio-heat simulation results show that for all evaluated antennas and frequency combinations we reach FCC SAR limits well before 1 °C. It is clear that powering neural interfaces via RF is possible, but ultra-low power circuit designs combined with advanced simulation will be required to develop a functional antenna that meets all system requirements. © 2013 Zhao et al

Photovoltaic Energy Harvesting for Millimeter-Scale Systems

The Internet of Things (IoT) based on mm-scale sensors is a transformational technology that opens up new capabilities for biomedical devices, surveillance, micro-robots and industrial monitoring. Energy harvesting approaches to power IoT have traditionally included thermal, vibration and radio frequency. However, the achievement of efficient energy scavenging for IoT at the mm-scale or sub mm-scale has been elusive. In this work, I show that photovoltaic (PV) cells at the mm-scale can be an alternative means of wireless power transfer to mm-scale sensors for IoT, utilizing ambient indoor lighting or intentional irradiation of near-infrared (NIR) LED sources through biological tissue. Single silicon and GaAs photovoltaic cells at the mm-scale can achieve a power conversion efficiency of more than 17 % for silicon and 30 % for GaAs under low-flux NIR irradiation at 850 nm through the optimized device structure and sidewall/surface passivation studies, which guarantees perpetual operation of mm-scale sensors. Furthermore, monolithic single-junction GaAs photovoltaic modules offer a means for series-interconnected cells to provide sufficient voltage (> 5 V) for direct battery charging, and bypassing needs for voltage up-conversion circuitry. However, there is a continuing challenge to miniaturize such PV systems down to the sub mm-scale with minimal optical losses from device isolation and metal interconnects and efficient voltage up-conversion. Vertically stacked dual-junction PV cells and modules are demonstrated to increase the output voltage per cell and minimize area losses for direct powering of miniature devices for IoT and bio-implantable applications with low-irradiance narrowband spectral illumination. Dual-junction PV cells at small dimensions (150 µm x 150 µm) demonstrate power conversion efficiency greater than 22 % with more than 1.2 V output voltage under low-flux 850 nm NIR LED illumination, which is sufficient for batteryless operation of miniaturized CMOS IC chips. The output voltage of dual-junction PV modules with eight series-connected single cells is greater than 10 V while maintaining an efficiency of more than 18 %. Finally, I demonstrate monolithic PV/LED modules at the µm-scale for brain-machine interfaces, enabling two-way optical power and data transfer in a through-tissue configuration. The wafer-level assembly plan for the 3D vertical integration of three different systems including GaAs LED/PV modules, CMOS silicon chips, and neural probes is proposed.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163261/1/esmoon_1.pd

Real-time signal detection and classification algorithms for body-centered systems

El principal motivo por el cual los sistemas de comunicación en el entrono corporal se desean con el objetivo de poder obtener y procesar señales biométricas para monitorizar e incluso tratar una condición médica sea ésta causada por una enfermedad o el rendimiento de un atleta. Dado que la base de estos sistemas está en la sensorización y el procesado, los algoritmos de procesado de señal son una parte fundamental de los mismos. Esta tesis se centra en los algoritmos de tratamiento de señales en tiempo real que se utilizan tanto para monitorizar los parámetros como para obtener la información que resulta relevante de las señales obtenidas. En la primera parte se introduce los tipos de señales y sensores en los sistemas en el entrono corporal. A continuación se desarrollan dos aplicaciones concretas de los sistemas en el entorno corporal así como los algoritmos que en las mismas se utilizan. La primera aplicación es el control de glucosa en sangre en pacientes con diabetes. En esta parte se desarrolla un método de detección mediante clasificación de patronones de medidas erróneas obtenidas con el monitor contínuo comercial "Minimed CGMS". La segunda aplicacióin consiste en la monitorizacióni de señales neuronales. Descubrimientos recientes en este campo han demostrado enormes posibilidades terapéuticas (por ejemplo, pacientes con parálisis total que son capaces de comunicarse con el entrono gracias a la monitorizacióin e interpretación de señales provenientes de sus neuronas) y también de entretenimiento. En este trabajo, se han desarrollado algoritmos de detección, clasificación y compresión de impulsos neuronales y dichos algoritmos han sido evaluados junto con técnicas de transmisión inalámbricas que posibiliten una monitorización sin cables. Por último, se dedica un capítulo a la transmisión inalámbrica de señales en los sistemas en el entorno corporal. En esta parte se estudia las condiciones del canal que presenta el entorno corporal para la transmisión de sTraver Sebastiá, L. (2012). Real-time signal detection and classification algorithms for body-centered systems [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/16188Palanci

Energy-Efficient Circuit Designs for Miniaturized Internet of Things and Wireless Neural Recording

Internet of Things (IoT) have become omnipresent over various territories including healthcare, smart building, agriculture, and environmental and industrial monitoring. Today, IoT are getting miniaturized, but at the same time, they are becoming more intelligent along with the explosive growth of machine learning. Not only do IoT sense and collect data and communicate, but they also edge-compute and extract useful information within the small form factor. A main challenge of such miniaturized and intelligent IoT is to operate continuously for long lifetime within its low battery capacity. Energy efficiency of circuits and systems is key to addressing this challenge. This dissertation presents two different energy-efficient circuit designs: a 224pW 260ppm/°C gate-leakage-based timer for wireless sensor nodes (WSNs) for the IoT and an energy-efficient all analog machine learning accelerator with 1.2 µJ/inference of energy consumption for the CIFAR-10 and SVHN datasets. Wireless neural interface is another area that demands miniaturized and energy-efficient circuits and systems for safe long-term monitoring of brain activity. Historically, implantable systems have used wires for data communication and power, increasing risks of tissue damage. Therefore, it has been a long-standing goal to distribute sub-mm-scale true floating and wireless implants throughout the brain and to record single-neuron-level activities. This dissertation presents a 0.19×0.17mm2 0.74µW wireless neural recording IC with near-infrared (NIR) power and data telemetry and a 0.19×0.28mm2 0.57µW light tolerant wireless neural recording IC.PHDElectrical and Computer EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169712/1/jongyup_1.pd

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

Microscale Infrared Technologies for Spectral Filtering and Wireless Neural Dust

Pivotal technologies, such as optical computing, autonomous vehicles, and biomedical implantables, motivate microscale infrared (IR) components. Hyperspectral imagers (HSI), for example, require compact and narrowband filters to obtain high-spatial and -spectral resolution images. HSIs acquire continuous spectra at each pixel, enabling non-destructive analyses by resolving IR scattering/absorption signatures. Toward this end, dielectric subwavelength gratings (SWG) are intriguing filter candidates since they are low-loss, have no moving parts, and exhibit narrow spectral features. Wireless neural implantables are another apropos microscale IR technology. Wireless IR data and power transfer disposes of infection-prone percutaneous wires by leveraging the IR transparency window in biological tissue. This dissertation contains two related topics. The first details SWG IR filters, and the second studies progress toward wireless neural motes. This work extends the capabilities of SWG IR filters. Following a theoretical overview, mid-wave infrared (MWIR, 3-7 um) transmittance filters are experimentally demonstrated using the zero-contrast grating scheme. Via a facile silicon fabrication process, we realize narrowband polarization-dependent and polarization-independent MWIR transmittance filters with some of the highest Q observed in MWIR SWGs. An empirical study confirms the relationship between filter performance and grating size, an important trade-off for HSIs. We then demonstrate GaAs SWG filters for monolithic integration with active optoelectronic devices. The GaAs SWGs perform comparably to their silicon counterparts. To enable narrowband filtering at normal incidence, we investigate symmetry-breaking in geometrically asymmetric gratings. The presented SWG geometries access quasi-bound states in the continuum (BIC). Studies in Fano resonance and diffraction efficiency symmetry provide physical insight. Asymmetric 1D and 2D SWGs furnish polarization-dependent and -independent filtering, respectively. We experimentally demonstrate normal incidence long-wave IR (LWIR, 7-12 um) transmittance filtering in asymmetric SWGs and confirm symmetry-breaking implications. A reduced-symmetry hexagonal pattern presents an early design for truly polarization-independent quasi-BIC coupling in SWGs. Advancements in implantable neural devices promise great leaps in brain mapping and therapeutic intervention. To meet this challenge, we investigated a wireless neural mote system using near-infrared (NIR, 800 nm – 3 um) photovoltaics and LEDs to wirelessly harvest power and transmit data. The neural recorders consist of three subsystems: an epitaxial GaAs-based optoelectronic chip, a Si CMOS IC, and a carbon fiber probe. Though this work encompasses the efforts of many, this dissertation outlines contributions in a few critical areas. To overcome low-flux LED emission, we devise an optical setup with ≈0.1% photon detection efficiency. Monte Carlo techniques model NIR scattering in biological tissue. Another steep challenge is the heterogeneous integration of the three material systems in a compact (200x170x150 um^3) package. To relay data and power between the GaAs and CMOS chips, through-wafer vias are critical. Using a novel selective copper plating technique, we demonstrate through-wafer GaAs vias with <2 Ohm series resistance. Additionally, conductive blind vias are presented for carbon fiber probe insertion. A self-aligned parylene etch mask permits sub-kOhm connection to a buried metal contact while maintaining GOhm substrate isolation. Both via structures meet the requirements of being low-resistance, insulated from the substrate, and amendable to thinned wafer processing. Finally, we demonstrate extensive processing on thinned chips and advances toward full heterogeneous integration via flip-chip alignment and solder bump bonding.PHDElectrical and Computer EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/169986/1/barrowm_1.pd

Physical principles for scalable neural recording

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic 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