Phase Synchronization Operator for On-Chip Brain Functional Connectivity Computation

This paper presents an integer-based digital processor for the calculation of phase synchronization between two neural signals. It is based on the measurement of time periods between two consecutive minima. The simplicity of the approach allows for the use of elementary digital blocks, such as registers, counters, and adders. The processor, fabricated in a 0.18- μ m CMOS process, only occupies 0.05 mm 2 and consumes 15 nW from a 0.5 V supply voltage at a signal input rate of 1024 S/s. These low-area and low-power features make the proposed processor a valuable computing element in closed-loop neural prosthesis for the treatment of neural disorders, such as epilepsy, or for assessing the patterns of correlated activity in neural assemblies through the evaluation of functional connectivity maps.Ministerio de Economía y Competitividad TEC2016-80923-POffice of Naval Research (USA) N00014-19-1-215

Sistema de predicción epileptogenica en lazo cerrado basado en matrices sub-durales

The human brain is the most complex organ in the human body, which consists of approximately 100 billion neurons. These cells effortlessly communicate over multiple hemispheres to deliver our everyday sensorimotor and cognitive abilities. Although the underlying principles of neuronal communication are not well understood, there is evidence to suggest precise synchronisation and/or de-synchronisation of neuronal clusters could play an important role. Furthermore, new evidence suggests that these patterns of synchronisation could be used as an identifier for the detection of a variety of neurological disorders including, Alzheimers (AD), Schizophrenia (SZ) and Epilepsy (EP), where neural degradation or hyper synchronous networks have been detected. Over the years many different techniques have been proposed for the detection of synchronisation patterns, in the form of spectral analysis, transform approaches and statistical based studies. Nonetheless, most are confined to software based implementations as opposed to hardware realisations due to their complexity. Furthermore, the few hardware implementations which do exist, suffer from a lack of scalability, in terms of brain area coverage, throughput and power consumption. Here we introduce the design and implementation of a hardware efficient algorithm, named Delay Difference Analysis (DDA), for the identification of patient specific synchronisation patterns. The design is remarkably hardware friendly when compared with other algorithms. In fact, we can reduce hardware requirements by as much as 80% and power consumption as much as 90%, when compared with the most common techniques. In terms of absolute sensitivity the DDA produces an average sensitivity of more than 80% for a false positive rate of 0.75 FP/h and indeed up to a maximum of 90% for confidence levels of 95%. This thesis presents two integer-based digital processors for the calculation of phase synchronisation between neural signals. It is based on the measurement of time periods between two consecutive minima. The simplicity of the approach allows for the use of elementary digital blocks, such as registers, counters or adders. In fact, the first introduced processor was fabricated in a 0.18μm CMOS process and only occupies 0.05mm2 and consumes 15nW from a 0.5V supply voltage at a signal input rate of 1024S/s. These low-area and low-power features make the proposed circuit a valuable computing element in closed-loop neural prosthesis for the treatment of neural disorders, such as epilepsy, or for measuring functional connectivity maps between different recording sites in the brain. A second VLSI implementation was designed and integrated as a mass integrated 16-channel design. Incorporated into the design were 16 individual synchronisation processors (15 on-line processors and 1 test processor) each with a dedicated training and calculation module, used to build a specialised epileptic detection system based on patient specific synchrony thresholds. Each of the main processors are capable of calculating the phase synchrony between 9 independent electroencephalography (EEG) signals over 8 epochs of time totalling 120 EEG combinations. Remarkably, the entire circuit occupies a total area of only 3.64 mm2. This design was implemented with a multi-purpose focus in mind. Firstly, as a clinical aid to help physicians detect pathological brain states, where the small area would allow the patient to wear the device for home trials. Moreover, the small power consumption would allow to run from standard batteries for long periods. The trials could produce important patient specific information which could be processed using mathematical tools such as graph theory. Secondly, the design was focused towards the use as an in-vivo device to detect phase synchrony in real time for patients who suffer with such neurological disorders as EP, which need constant monitoring and feedback. In future developments this synchronisation device would make an good contribution to a full system on chip device for detection and stimulation.El cerebro humano es el órgano más complejo del cuerpo humano, que consta de aproximadamente 100 mil millones de neuronas. Estas células se comunican sin esfuerzo a través de ambos hemisferios para favorecer nuestras habilidades sensoriales y cognitivas diarias. Si bien los principios subyacentes de la comunicación neuronal no se comprenden bien, existen pruebas que sugieren que la sincronización precisa y/o la desincronización de los grupos neuronales podrían desempeñar un papel importante. Además, nuevas evidencias sugieren que estos patrones de sincronización podrían usarse como un identificador para la detección de una gran variedad de trastornos neurológicos incluyendo la enfermedad de Alzheimer(AD), la esquizofrenia(SZ) y la epilepsia(EP), donde se ha detectado la degradación neural o las redes hiper sincrónicas. A lo largo de los años, se han propuesto muchas técnicas diferentes para la detección de patrones de sincronización en forma de análisis espectral, enfoques de transformación y análisis estadísticos. No obstante, la mayoría se limita a implementaciones basadas en software en lugar de realizaciones de hardware debido a su complejidad. Además, las pocas implementaciones de hardware que existen, sufren una falta de escalabilidad, en términos de cobertura del área del cerebro, rendimiento y consumo de energía. Aquí presentamos el diseño y la implementación de un algoritmo eficiente de hardware llamado “Delay Difference Aproximation” (DDA) para la identificación de patrones de sincronización específicos del paciente. El diseño es notablemente compatible con el hardware en comparación con otros algoritmos. De hecho, podemos reducir los requisitos de hardware hasta en un 80% y el consumo de energía hasta en un 90%, en comparación con las técnicas más comunes. En términos de sensibilidad absoluta, la DDA produce una sensibilidad promedio de más del 80% para una tasa de falsos positivos de 0,75 PF / hr y hasta un máximo del 90% para niveles de confianza del 95%. Esta tesis presenta dos procesadores digitales para el cálculo de la sincronización de fase entre señales neuronales. Se basa en la medición de los períodos de tiempo entre dos mínimos consecutivos. La simplicidad del enfoque permite el uso de bloques digitales elementales, como registros, contadores o sumadores. De hecho, el primer procesador introducido se fabricó en un proceso CMOS de 0.18μm y solo ocupa 0.05mm2 y consume 15nW de un voltaje de suministro de 0.5V a una tasa de entrada de señal de 1024S/s Estas características de baja área y baja potencia hacen que el procesador propuesto sea un valioso elemento informático en prótesis neurales de circuito cerrado para el tratamiento de trastornos neuronales, como la epilepsia, o para medir mapas de conectividad funcional entre diferentes sitios de registro en el cerebro. Además, se diseñó una segunda implementación VLSI que se integró como un diseño de 16 canales integrado en masa. Se incorporaron al diseño 16 procesadores de sincronización individuales (15 procesadores en línea y 1 procesador de prueba), cada uno con un módulo de entrenamiento y cálculo dedicado, utilizado para construir un sistema de detección epiléptico especializado basado en umbrales de sincronía específicos del paciente. Cada uno de los procesadores principales es capaz de calcular la sincronización de fase entre 9 señales de electroencefalografía (EEG) independientes en 8 épocas de tiempo que totalizan 120 combinaciones de EEG. Cabe destacar que todo el circuito ocupa un área total de solo 3.64 mm2. Este diseño fue implementado teniendo en mente varios propósitos. En primer lugar, como ayuda clínica para ayudar a los médicos a detectar estados cerebrales patológicos, donde el área pequeña permitiría al paciente usar el dispositivo para las pruebas caseras. Además, el pequeño consumo de energía permitiría una carga cero del dispositivo, lo que le permitiría funcionar con baterías estándar durante largos períodos. Los ensayos podrían producir información importante específica para el paciente que podría procesarse utilizando herramientas matemáticas como la teoría de grafos. En segundo lugar, el diseño se centró en el uso como un dispositivo in-vivo para detectar la sincronización de fase en tiempo real para pacientes que sufren trastornos neurológicos como el EP, que necesitan supervisión y retroalimentación constantes. En desarrollos futuros, este dispositivo de sincronización sería una buena base para desarrollar un sistema completo de un dispositivo chip para detección de trastornos neurológicos

Low Power Circuits for Smart Flexible ECG Sensors

Cardiovascular diseases (CVDs) are the world leading cause of death. In-home heart condition monitoring effectively reduced the CVD patient hospitalization rate. Flexible electrocardiogram (ECG) sensor provides an affordable, convenient and comfortable in-home monitoring solution. The three critical building blocks of the ECG sensor i.e., analog frontend (AFE), QRS detector, and cardiac arrhythmia classifier (CAC), are studied in this research. A fully differential difference amplifier (FDDA) based AFE that employs DC-coupled input stage increases the input impedance and improves CMRR. A parasitic capacitor reuse technique is proposed to improve the noise/area efficiency and CMRR. An on-body DC bias scheme is introduced to deal with the input DC offset. Implemented in 0.35m CMOS process with an area of 0.405mm2, the proposed AFE consumes 0.9W at 1.8V and shows excellent noise effective factor of 2.55, and CMRR of 76dB. Experiment shows the proposed AFE not only picks up clean ECG signal with electrodes placed as close as 2cm under both resting and walking conditions, but also obtains the distinct -wave after eye blink from EEG recording. A personalized QRS detection algorithm is proposed to achieve an average positive prediction rate of 99.39% and sensitivity rate of 99.21%. The user-specific template avoids the complicate models and parameters used in existing algorithms while covers most situations for practical applications. The detection is based on the comparison of the correlation coefficient of the user-specific template with the ECG segment under detection. The proposed one-target clustering reduced the required loops. A continuous-in-time discrete-in-amplitude (CTDA) artificial neural network (ANN) based CAC is proposed for the smart ECG sensor. The proposed CAC achieves over 98% classification accuracy for 4 types of beats defined by AAMI (Association for the Advancement of Medical Instrumentation). The CTDA scheme significantly reduces the input sample numbers and simplifies the sample representation to one bit. Thus, the number of arithmetic operations and the ANN structure are greatly simplified. The proposed CAC is verified by FPGA and implemented in 0.18m CMOS process. Simulation results show it can operate at clock frequencies from 10KHz to 50MHz. Average power for the patient with 75bpm heart rate is 13.34W

Bidirectional Neural Interface Circuits with On-Chip Stimulation Artifact Reduction Schemes

Bidirectional neural interfaces are tools designed to “communicate” with the brain via recording and modulation of neuronal activity. The bidirectional interface systems have been adopted for many applications. Neuroscientists employ them to map neuronal circuits through precise stimulation and recording. Medical doctors deploy them as adaptable medical devices which control therapeutic stimulation parameters based on monitoring real-time neural activity. Brain-machine-interface (BMI) researchers use neural interfaces to bypass the nervous system and directly control neuroprosthetics or brain-computer-interface (BCI) spellers. In bidirectional interfaces, the implantable transducers as well as the corresponding electronic circuits and systems face several challenges. A high channel count, low power consumption, and reduced system size are desirable for potential chronic deployment and wider applicability. Moreover, a neural interface designed for robust closed-loop operation requires the mitigation of stimulation artifacts which corrupt the recorded signals. This dissertation introduces several techniques targeting low power consumption, small size, and reduction of stimulation artifacts. These techniques are implemented for extracellular electrophysiological recording and two stimulation modalities: direct current stimulation for closed-loop control of seizure detection/quench and optical stimulation for optogenetic studies. While the two modalities differ in their mechanisms, hardware implementation, and applications, they share many crucial system-level challenges. The first method aims at solving the critical issue of stimulation artifacts saturating the preamplifier in the recording front-end. To prevent saturation, a novel mixed-signal stimulation artifact cancellation circuit is devised to subtract the artifact before amplification and maintain the standard input range of a power-hungry preamplifier. Additional novel techniques have been also implemented to lower the noise and power consumption. A common average referencing (CAR) front-end circuit eliminates the cross-channel common mode noise by averaging and subtracting it in analog domain. A range-adapting SAR ADC saves additional power by eliminating unnecessary conversion cycles when the input signal is small. Measurements of an integrated circuit (IC) prototype demonstrate the attenuation of stimulation artifacts by up to 42 dB and cross-channel noise suppression by up to 39.8 dB. The power consumption per channel is maintained at 330 nW, while the area per channel is only 0.17 mm2. The second system implements a compact headstage for closed-loop optogenetic stimulation and electrophysiological recording. This design targets a miniaturized form factor, high channel count, and high-precision stimulation control suitable for rodent in-vivo optogenetic studies. Monolithically integrated optoelectrodes (which include 12 µLEDs for optical stimulation and 12 electrical recording sites) are combined with an off-the-shelf recording IC and a custom-designed high-precision LED driver. 32 recording and 12 stimulation channels can be individually accessed and controlled on a small headstage with dimensions of 2.16 x 2.38 x 0.35 cm and mass of 1.9 g. A third system prototype improves the optogenetic headstage prototype by furthering system integration and improving power efficiency facilitating wireless operation. The custom application-specific integrated circuit (ASIC) combines recording and stimulation channels with a power management unit, allowing the system to be powered by an ultra-light Li-ion battery. Additionally, the µLED drivers include a high-resolution arbitrary waveform generation mode for shaping of µLED current pulses to preemptively reduce artifacts. A prototype IC occupies 7.66 mm2, consumes 3.04 mW under typical operating conditions, and the optical pulse shaping scheme can attenuate stimulation artifacts by up to 3x with a Gaussian-rise pulse rise time under 1 ms.PHDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147674/1/mendrela_1.pd

Compressed sensing based seizure detection for an ultra low power multi-core architecture

Extracting information from brain signals in advanced Brain Machine Interfaces (BMI) often requires computationally demanding processing. The complexity of the algorithms traditionally employed to process multi-channel neural data, such as Principal Component Analysis (PCA), dramatically increases while scaling-up the number of channels and requires more power-hungry computational platforms. This could hinder the development of low-cost and low-power interfaces which can be used in wearable or implantable real-Time systems. This work proposes a new algorithm for the detection of epileptic seizure based on compressively sensed EEG information, and its optimization on a low-power multi-core SoC for near-sensor data analytics: Mr. Wolf. With respect to traditional algorithms based on PCA, the proposed approach reduces the computational complexity by 4.4x in ARM Cortex M4-based MCU. Implementing this algorithm on Mr.Wolf platform allows to detect a seizure with 1 ms of latency after acquiring the EEG data for 1 s, within an energy budget of 18.4 μJ. A comparison with the same algorithm on a commercial MCU shows an improvement of 6.9x in performance and up to 18.4x in terms of energy efficiency

MR-compatible Electrophysiology Recording System for Multimodal Imaging

Simultaneous acquisition of functional magnetic resonance imaging (fMRI) and electrophysiological recordings is an emerging multimodal neuroimaging strategy for studying brain functions. However, the strong magnetic field generated during fMRI greatly degrades the electrophysiological signal quality during simultaneous acquisition. Here, I developed a low powered, miniaturized, system – “ECHO” which delivers a hardware and software solution to overcome the challenges presented by multimodal imaging. The device monitors fluctuations in electromagnetic field during fMRI and synchronizes amplification and sampling of electrophysiological signals to minimize effects of gradient and RF artifacts (electromagnetic artifacts). Furthermore, I introduced a concept of wirelessly transmitting recorded data through the MRI receiver coil. ECHO transmits the data at a frequency visible to the MRI receiver coil, after which the transmitted data is readily separable from the MRI image in the frequency domain. The MR-compatibility of the recorder was evaluated through a series of experiments with a phantom to study its effects on the MRI image quality. To further evaluate the effectiveness of ECHO, I recorded electrocardiogram and local field potential (evoked potential) in live rats during concurrent fMRI acquisition. In summary, ECHO offers a ‘plug and play’ solution to capture artifact-free electrophysiological data without the need of expensive amplifiers or synchronization hardware which require physical connection to the MRI scanner. This device is expected to make multimodal imaging more accessible and be applied for a broad range of fMRI studies in both the research and clinical fields

Advanced Interfaces for HMI in Hand Gesture Recognition

The present thesis investigates techniques and technologies for high quality Human Machine Interfaces (HMI) in biomedical applications. Starting from a literature review and considering market SoA in this field, the thesis explores advanced sensor interfaces, wearable computing and machine learning techniques for embedded resource-constrained systems. The research starts from the design and implementation of a real-time control system for a multifinger hand prosthesis based on pattern recognition algorithms. This system is capable to control an artificial hand using a natural gesture interface, considering the challenges related to the trade-off between responsiveness, accuracy and light computation. Furthermore, the thesis addresses the challenges related to the design of a scalable and versatile system for gesture recognition with the integration of a novel sensor interface for wearable medical and consumer application

Ultra-low power mixed-signal frontend for wearable EEGs

Electronics circuits are ubiquitous in daily life, aided by advancements in the chip design industry, leading to miniaturised solutions for typical day to day problems. One of the critical healthcare areas helped by this advancement in technology is electroencephalography (EEG). EEG is a non-invasive method of tracking a person's brain waves, and a crucial tool in several healthcare contexts, including epilepsy and sleep disorders. Current ambulatory EEG systems still suffer from limitations that affect their usability. Furthermore, many patients admitted to emergency departments (ED) for a neurological disorder like altered mental status or seizures, would remain undiagnosed hours to days after admission, which leads to an elevated rate of death compared to other conditions. Conducting a thorough EEG monitoring in early-stage could prevent further damage to the brain and avoid high mortality. But lack of portability and ease of access results in a long wait time for the prescribed patients. All real signals are analogue in nature, including brainwaves sensed by EEG systems. For converting the EEG signal into digital for further processing, a truly wearable EEG has to have an analogue mixed-signal front-end (AFE). This research aims to define the specifications for building a custom AFE for the EEG recording and use that to review the suitability of the architectures available in the literature. Another critical task is to provide new architectures that can meet the developed specifications for EEG monitoring and can be used in epilepsy diagnosis, sleep monitoring, drowsiness detection and depression study. The thesis starts with a preview on EEG technology and available methods of brainwaves recording. It further expands to design requirements for the AFE, with a discussion about critical issues that need resolving. Three new continuous-time capacitive feedback chopped amplifier designs are proposed. A novel calibration loop for setting the accurate value for a pseudo-resistor, which is a crucial block in the proposed topology, is also discussed. This pseudoresistor calibration loop achieved the resistor variation of under 8.25%. The thesis also presents a new design of a curvature corrected bandgap, as well as a novel DDA based fourth-order Sallen-Key filter. A modified sensor frontend architecture is then proposed, along with a detailed analysis of its implementation. Measurement results of the AFE are finally presented. The AFE consumed a total power of 3.2A (including ADC, amplifier, filter, and current generation circuitry) with the overall integrated input-referred noise of 0.87V-rms in the frequency band of 0.5-50Hz. Measurement results confirmed that only the proposed AFE achieved all defined specifications for the wearable EEG system with the smallest power consumption than state-of-art architectures that meet few but not all specifications. The AFE also achieved a CMRR of 131.62dB, which is higher than any studied architectures.Open Acces

Wearable electroencephalography for long-term monitoring and diagnostic purposes

Truly Wearable EEG (WEEG) can be considered as the future of ambulatory EEG units, which are the current standard for long-term EEG monitoring. Replacing these short lifetime, bulky units with long-lasting, miniature and wearable devices that can be easily worn by patients will result in more EEG data being collected for extended monitoring periods. This thesis presents three new fabricated systems, in the form of Application Specific Integrated Circuits (ASICs), to aid the diagnosis of epilepsy and sleep disorders by detecting specific clinically important EEG events on the sensor node, while discarding background activity. The power consumption of the WEEG monitoring device incorporating these systems can be reduced since the transmitter, which is the dominating element in terms of power consumption, will only become active based on the output of these systems. Candidate interictal activity is identified by the developed analog-based interictal spike selection system-on-chip (SoC), using an approximation of the Continuous Wavelet Transform (CWT), as a bandpass filter, and thresholding. The spike selection SoC is fabricated in a 0.35 μm CMOS process and consumes 950 nW. Experimental results reveal that the SoC is able to identify 87% of interictal spikes correctly while only transmitting 45% of the data. Sections of EEG data containing likely ictal activity are detected by an analog seizure selection SoC using the low complexity line length feature. This SoC is fabricated in a 0.18 μm CMOS technology and consumes 1.14 μW. Based on experimental results, the fabricated SoC is able to correctly detect 83% of seizure episodes while transmitting 52% of the overall EEG data. A single-channel analog-based sleep spindle detection SoC is developed to aid the diagnosis of sleep disorders by detecting sleep spindles, which are characteristic events of sleep. The system identifies spindle events by monitoring abrupt changes in the input EEG. An approximation of the median frequency calculation, incorporated as part of the system, allows for non-spindle activity incorrectly identified by the system as sleep spindles to be discarded. The sleep spindle detection SoC is fabricated in a 0.18 μm CMOS technology, consuming only 515 nW. The SoC achieves a sensitivity and specificity of 71.5% and 98% respectively.Open Acces