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

Low-Noise Micro-Power Amplifiers for Biosignal Acquisition

There are many different types of biopotential signals, such as action potentials (APs), local field potentials (LFPs), electromyography (EMG), electrocardiogram (ECG), electroencephalogram (EEG), etc. Nerve action potentials play an important role for the analysis of human cognition, such as perception, memory, language, emotions, and motor control. EMGs provide vital information about the patients which allow clinicians to diagnose and treat many neuromuscular diseases, which could result in muscle paralysis, motor problems, etc. EEGs is critical in diagnosing epilepsy, sleep disorders, as well as brain tumors. Biopotential signals are very weak, which requires the biopotential amplifier to exhibit low input-referred noise. For example, EEGs have amplitudes from 1 μV [microvolt] to 100 μV [microvolt] with much of the energy in the sub-Hz [hertz] to 100 Hz [hertz] band. APs have amplitudes up to 500 μV [microvolt] with much of the energy in the 100 Hz [hertz] to 7 kHz [hertz] band. In wearable/implantable systems, the low-power operation of the biopotential amplifier is critical to avoid thermal damage to surrounding tissues, preserve long battery life, and enable wirelessly-delivered or harvested energy supply. For an ideal thermal-noise-limited amplifier, the amplifier power is inversely proportional to the input-referred noise of the amplifier. Therefore, there is a noise-power trade-off which must be well-balanced by the designers. In this work I propose novel amplifier topologies, which are able to significantly improve the noise-power efficiency by increasing the effective transconductance at a given current. In order to reject the DC offsets generated at the tissue-electrode interface, energy-efficient techniques are employed to create a low-frequency high-pass cutoff. The noise contribution of the high-pass cutoff circuitry is minimized by using power-efficient configurations, and optimizing the biasing and dimension of the devices. Sufficient common-mode rejection ratio (CMRR) and power supply rejection ratio (PSRR) are achieved to suppress common-mode interferences and power supply noises. Our design are fabricated in standard CMOS processes. The amplifiers’ performance are measured on the bench, and also demonstrated with biopotential recordings

Recent Advances in Neural Recording Microsystems

The accelerating pace of research in neuroscience has created a considerable demand for neural interfacing microsystems capable of monitoring the activity of large groups of neurons. These emerging tools have revealed a tremendous potential for the advancement of knowledge in brain research and for the development of useful clinical applications. They can extract the relevant control signals directly from the brain enabling individuals with severe disabilities to communicate their intentions to other devices, like computers or various prostheses. Such microsystems are self-contained devices composed of a neural probe attached with an integrated circuit for extracting neural signals from multiple channels, and transferring the data outside the body. The greatest challenge facing development of such emerging devices into viable clinical systems involves addressing their small form factor and low-power consumption constraints, while providing superior resolution. In this paper, we survey the recent progress in the design and the implementation of multi-channel neural recording Microsystems, with particular emphasis on the design of recording and telemetry electronics. An overview of the numerous neural signal modalities is given and the existing microsystem topologies are covered. We present energy-efficient sensory circuits to retrieve weak signals from neural probes and we compare them. We cover data management and smart power scheduling approaches, and we review advances in low-power telemetry. Finally, we conclude by summarizing the remaining challenges and by highlighting the emerging trends in the field

A 23μW Solar-Powered Keyword-Spotting ASIC with Ring-Oscillator-Based Time-Domain Feature Extraction

Voice-controlled interfaces on acoustic Internet-of-Things (IoT) sensor nodes and mobile devices require integrated low-power always-on wake-up functions such as Voice Activity Detection (VAD) and Keyword Spotting (KWS) to ensure longer battery life. Most VAD and KWS ICs focused on reducing the power of the feature extractor (FEx) as it is the most power-hungry building block. A serial Fast Fourier Transform (FFT)-based KWS chip [1] achieved 510nW; however, it suffered from a high 64ms latency and was limited to detection of only 1-to-4 keywords (2-to-5 classes). Although the analog FEx [2]–[3] for VAD/KWS reported 0.2μW-to-1 μW and 10ms-to-100ms latency, neither demonstrated >5 classes in keyword detection. In addition, their voltage-domain implementations cannot benefit from process scaling because the low supply voltage reduces signal swing; and the degradation of intrinsic gain forces transistors to have larger lengths and poor linearity

Advances in Microelectronics for Implantable Medical Devices

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

Realization of Integrable Low- Voltage Companding Filters for Portable System Applications

Undoubtedly, today’s integrated electronic systems owe their remarkable performance primarily to the rapid advancements of digital technology since 1970s. The various important advantages of digital circuits are: its abstraction from the physical details of the actual circuit implementation, its comparative insensitiveness to variations in the manufacturing process, and the operating conditions besides allowing functional complexity that would not be possible using analog technology. As a result, digital circuits usually offer a more robust behaviour than their analog counterparts, though often with area, power and speed drawbacks. Due to these and other benefits, analog functionality has increasingly been replaced by digital implementations. In spite of the advantages discussed above, analog components are far from obsolete and continue to be key components of modern electronic systems. There is a definite trend toward persistent and ubiquitous use of analog electronic circuits in day-to-day life. Portable electronic gadgets, wireless communications and the widespread application of RF tags are just a few examples of contemporary developments. While all of these electronic systems are based on digital circuitry, they heavily rely on analog components as interfaces to the real world. In fact, many modern designs combine powerful digital systems and complementary analog components on a single chip for cost and reliability reasons. Unfortunately, the design of such systems-on-chip (SOC) suffers from the vastly different design styles of analog and digital components. While mature synthesis tools are readily available for digital designs, there is hardly any such support for analog designers apart from wellestablished PSPICE-like circuit simulators. Consequently, though the analog part usually occupies only a small fraction of the entire die area of an SOC, but its design often constitutes a major bottleneck within the entire development process. Integrated continuous-time active filters are the class of continuous-time or analog circuits which are used in various applications like channel selection in radios, anti-aliasing before sampling, and hearing aids etc. One of the figures of merit of a filter is the dynamic range; this is the ratio of the largest to the smallest signal that can be applied at the input of the filter while maintaining certain specified performance. The dynamic range required in the filter varies with the application and is decided by the variation in strength of the desired signal as well as that of unwanted signals that are to be rejected by the filter. It is well known that the power dissipation and the capacitor area of an integrated active filter increases in proportion to its dynamic range. This situation is incompatible with the needs of integrated systems, especially battery operated ones. In addition to this fundamental dependence of power dissipation on dynamic range, the design of integrated active filters is further complicated by the reduction of supply voltage of integrated circuits imposed by the scaling down of technologies to attain twin objective of higher speed and lower power consumption in digital circuits. The reduction in power consumption with decreasing supply voltage does not apply to analog circuits. In fact, considerable innovation is required with a reduced supply voltage even to avoid increasing power consumption for a given signal to noise ratio (S/N). These aspects pose a great hurdle to the active filter designer. A technique which has attracted the attention of circuit designers as a possible route to filters with higher dynamic range per unit power consumption is “companding”. Companding (compression-expansion) filters are a very promising subclass of continuous-time analog filters, where the input (linear) signal is initially compressed before it will be handled by the core (non-linear) system. In order to preserve the linear operation of the whole system, the non-linear signal produced by the core system is converted back to a linear output signal by employing an appropriate output stage. The required compression and expansion operations are performed by employing bipolar transistors in active region or MOS transistors in weak inversion; the systems thus derived are known as logarithmic-domain (logdomain) systems. In case MOS transistors operated in saturation region are employed, the derived structures are known as Square-root domain systems. Finally, the third class of companding filters can also be obtained by employing bipolar transistors in active region or MOS transistors in weak inversion; the derived systems are known as Sinh-domain systems. During the last several years, a significant research effort has been already carried out in the area of companding circuits. This is due to the fact that their main advantages are the capability for operation in low-voltage environment and large dynamic range originated from their companding nature, electronic tunability of the frequency characteristics, absence of resistors and the potential for operations in varied frequency regions.Thus, it is obvious that companding filters can be employed for implementing high-performance analog signal processing in diverse frequency ranges. For example, companding filters could be used for realizing subsystems in: xDSL modems, disk drive read channels, biomedical electronics, Bluetooth/ZigBee applications, phaselocked loops, FM stereo demodulator, touch-tone telephone tone decoder and crossover network used in a three-way high-fidelity loudspeaker etc. A number of design methods for companding filters and their building blocks have been introduced in the literature. Most of the proposed filter structures operate either above 1.5V or under symmetrical (1.5V) power supplies. According to data that provides information about the near future of semiconductor technology, International Technology Roadmap for Semiconductors (ITRS), in 2013, the supply voltage of digital circuits in 32 nm technology will be 0.5 V. Therefore, the trend for the implementation of analog integrated circuits is the usage of low-voltage building blocks that use a single 0.5-1.5V power supply. Therefore, the present investigation was primarily concerned with the study and design of low voltage and low power Companding filters. The work includes the study about: the building blocks required in implementing low voltage and low power Companding filters; the techniques used to realize low voltage and low power Companding filters and their various areas of application. Various novel low voltage and low power Companding filter designs have been developed and studied for their characteristics to be applied in a particular portable area of application. The developed designs include the N-th order universal Companding filter designs, which have been reported first time in the open literature. Further, an endeavor has been made to design Companding filters with orthogonal tuning of performance parameters so that the designs can be simultaneously used for various features. The salient features of each of the developed circuit are described. Electronic tunability is one of the major features of all of the designs. Use of grounded capacitors and resistorless designs in all the cases makes the designs suitable for IC technology. All the designs operate in a low-voltage and low-power environment essential for portable system applications. Unless specified otherwise, all the investigations on these designs are based on the PSPICE simulations using model parameters of the NR100N bipolar transistors and BSIM 0.35μm/TSMC 0.25μm /TSMC 0.18μm CMOS process MOS transistors. The performance of each circuit has been validated by comparing the characteristics obtained using simulation with the results present in the open literature. The proposed designs could not be realized in silicon due to non-availability of foundry facility at the place of study. An effort has already been started to realize some of the designs in silicon and check their applicability in practical circuits. At the basic level, one of the proposed Companding filter designs was implemented using the commercially available transistor array ICs (LM3046N) and was found to verify the theoretical predictions obtained from the simulation results

Low-Power Low-Noise CMOS Analog and Mixed-Signal Design towards Epileptic Seizure Detection

About 50 million people worldwide suffer from epilepsy and one third of them have seizures that are refractory to medication. In the past few decades, deep brain stimulation (DBS) has been explored by researchers and physicians as a promising way to control and treat epileptic seizures. To make the DBS therapy more efficient and effective, the feedback loop for titrating therapy is required. It means the implantable DBS devices should be smart enough to sense the brain signals and then adjust the stimulation parameters adaptively. This research proposes a signal-sensing channel configurable to various neural applications, which is a vital part for a future closed-loop epileptic seizure stimulation system. This doctoral study has two main contributions, 1) a micropower low-noise neural front-end circuit, and 2) a low-power configurable neural recording system for both neural action-potential (AP) and fast-ripple (FR) signals. The neural front end consists of a preamplifier followed by a bandpass filter (BPF). This design focuses on improving the noise-power efficiency of the preamplifier and the power/pole merit of the BPF at ultra-low power consumption. In measurement, the preamplifier exhibits 39.6-dB DC gain, 0.8 Hz to 5.2 kHz of bandwidth (BW), 5.86-μVrms input-referred noise in AP mode, while showing 39.4-dB DC gain, 0.36 Hz to 1.3 kHz of BW, 3.07-μVrms noise in FR mode. The preamplifier achieves noise efficiency factor (NEF) of 2.93 and 3.09 for AP and FR modes, respectively. The preamplifier power consumption is 2.4 μW from 2.8 V for both modes. The 6th-order follow-the-leader feedback elliptic BPF passes FR signals and provides -110 dB/decade attenuation to out-of-band interferers. It consumes 2.1 μW from 2.8 V (or 0.35 μW/pole) and is one of the most power-efficient high-order active filters reported to date. The complete front-end circuit achieves a mid-band gain of 38.5 dB, a BW from 250 to 486 Hz, and a total input-referred noise of 2.48 μVrms while consuming 4.5 μW from the 2.8 V power supply. The front-end NEF achieved is 7.6. The power efficiency of the complete front-end is 0.75 μW/pole. The chip is implemented in a standard 0.6-μm CMOS process with a die area of 0.45 mm^2. The neural recording system incorporates the front-end circuit and a sigma-delta analog-to-digital converter (ADC). The ADC has scalable BW and power consumption for digitizing both AP and FR signals captured by the front end. Various design techniques are applied to the improvement of power and area efficiency for the ADC. At 77-dB dynamic range (DR), the ADC has a peak SNR and SNDR of 75.9 dB and 67 dB, respectively, while consuming 2.75-mW power in AP mode. It achieves 78-dB DR, 76.2-dB peak SNR, 73.2-dB peak SNDR, and 588-μW power consumption in FR mode. Both analog and digital power supply voltages are 2.8 V. The chip is fabricated in a standard 0.6-μm CMOS process. The die size is 11.25 mm^2. The proposed circuits can be extended to a multi-channel system, with the ADC shared by all channels, as the sensing part of a future closed-loop DBS system for the treatment of intractable epilepsy

An electronic neuromorphic system for real-time detection of High Frequency Oscillations (HFOs) in intracranial EEG

In this work, we present a neuromorphic system that combines for the first time a neural recording headstage with a signal-to-spike conversion circuit and a multi-core spiking neural network (SNN) architecture on the same die for recording, processing, and detecting High Frequency Oscillations (HFO), which are biomarkers for the epileptogenic zone. The device was fabricated using a standard 0.18$\mu$m CMOS technology node and has a total area of 99mm$^{2}$. We demonstrate its application to HFO detection in the iEEG recorded from 9 patients with temporal lobe epilepsy who subsequently underwent epilepsy surgery. The total average power consumption of the chip during the detection task was 614.3$\mu$W. We show how the neuromorphic system can reliably detect HFOs: the system predicts postsurgical seizure outcome with state-of-the-art accuracy, specificity and sensitivity (78%, 100%, and 33% respectively). This is the first feasibility study towards identifying relevant features in intracranial human data in real-time, on-chip, using event-based processors and spiking neural networks. By providing "neuromorphic intelligence" to neural recording circuits the approach proposed will pave the way for the development of systems that can detect HFO areas directly in the operation room and improve the seizure outcome of epilepsy surgery.Comment: 16 pages. A short video describing the rationale underlying the study can be viewed on https://youtu.be/NuAA91fdma

CMOS Hyperbolic Sine ELIN filters for low/audio frequency biomedical applications

Hyperbolic-Sine (Sinh) filters form a subclass of Externally-Linear-Internally-Non- Linear (ELIN) systems. They can handle large-signals in a low power environment under half the capacitor area required by the more popular ELIN Log-domain filters. Their inherent class-AB nature stems from the odd property of the sinh function at the heart of their companding operation. Despite this early realisation, the Sinh filtering paradigm has not attracted the interest it deserves to date probably due to its mathematical and circuit-level complexity. This Thesis presents an overview of the CMOS weak inversion Sinh filtering paradigm and explains how biomedical systems of low- to audio-frequency range could benefit from it. Its dual scope is to: consolidate the theory behind the synthesis and design of high order Sinh continuous–time filters and more importantly to confirm their micro-power consumption and 100+ dB of DR through measured results presented for the first time. Novel high order Sinh topologies are designed by means of a systematic mathematical framework introduced. They employ a recently proposed CMOS Sinh integrator comprising only p-type devices in its translinear loops. The performance of the high order topologies is evaluated both solely and in comparison with their Log domain counterparts. A 5th order Sinh Chebyshev low pass filter is compared head-to-head with a corresponding and also novel Log domain class-AB topology, confirming that Sinh filters constitute a solution of equally high DR (100+ dB) with half the capacitor area at the expense of higher complexity and power consumption. The theoretical findings are validated by means of measured results from an 8th order notch filter for 50/60Hz noise fabricated in a 0.35μm CMOS technology. Measured results confirm a DR of 102dB, a moderate SNR of ~60dB and 74μW power consumption from 2V power supply

Current efficient integrated architecture for common mode rejection sensitive neural recordings

In the last decade we have seen a significant growth of research and potential applications of electronic circuits that interact with the nervous system, in a wide range of applications, from basic neuroscience research to medical clinic, or from the entertainment industry to transport services. The real time acquisition and analysis of brain signals, either through wearable electroencephalography (EEG) or invasive or implantable recordings, in order to perform actions (brain machine interface) or to understand aspects of brain operation, has become scientifically and technologically feasible. This thesis aims to support neural recording applications with low noise, currentefficiency and high common-mode rejection ratio (CMRR) as main features of the recording system. One emblematic example of these applications in the neuroscience domain is the weakly electric fish neural activity recording, where the interference produced by the discharge of the fish electric organ is a key factor. Another example, from the implantable devices domain, is the nerve activity recorded with cuff electrodes, where the desired signal is interfered by electromyographic potentials generated by muscles near the cuff. In these cases, the amplitude of the interfering signals, which mainly appear in common mode, is several orders of magnitude higher than the amplitude of the signals of interest. Therefore, this thesis introduces a novel integrated neural preamplifier architecture targeting CMRR sensitive neural recording applications. The architecture is presented and analyzed in depth, deriving the preamplifier transfer function and the main design equations. We present a detailed analysis of a technique for blocking the input dc component and setting the high-pass frequency without using MOS pseudo-resistors. One of the main contributions of this work is the overall architecture coupled with an efficient and simple single-stage circuit for the preamplifier main transconductor. A fully-integrated neural preamplifier, which performs well in line with the state-ofthe-art of the field while providing enhanced CMRR performance, was fabricated in a 0.5 um CMOS process. Results from measurements show that the measured gain is 49.5 dB, bandwidth ranges from 13 Hz to 9.8 kHz, CMRR is very high (greater than 87 dB), and it is achieved jointly with a remarkable low noise (1.88 uVrms) and current-efficiency (NEF = noise efficiency factor = 2.1). A second version of the preamplifier with one external capacitor achieves a high-pass frequency of 0.1 Hz while keeping the performance of the fully-integrated version. In addition, we present in-vivo measurements made with the proposed architecture in a weakly electric fish (Gymnotus omarorum), showing the ability of the preamplifier to acquire neural signals from high amplitude common mode interference in an unshielded environment. This was the first in-vivo testing of a neural recording integrated circuit designed in Uruguay done in a local lab. Furthermore, signals recorded with our unshielded low-power battery-powered preamplifier perfectly match with those of a shielded commercially-available amplifier (ac-plugged, without power restrictions). To the best of our knowledge, the proposed preamplifier is the best option for applications that simultaneously need low noise, high CMRR and current-efficiency. Furthermore, in this thesis we applied the aforementioned architecture to bandpass biquad filters, specially but not only, to those with differential input. The new architecture provides a significant reduction in consumption (up to 30%) and/or makes it possible to block a higher level of dc at the input (up to the double, without using decoupling capacitors). Next, we applied the novel architecture to the design of the different stages of an integrated programmable analog front-end. Results from simulations shows that the gain is programmable between 57 dB and 99 dB, the low-pass frequency is programmable between 116 Hz and 5.2 kHz, the maximum power consumption is 11.2 uA and the maximum equivalent input-referred noise voltage is 1.87 uVrms. The comparison between our front-end and other works in the state-of-the-art shows that our front-end presents the best results in terms of CMRR and noise, has the greatest value of gain and equals the best NEF reported. Finally, some system-level topics were addressed during this thesis, including the design and implementation of three prototypes of end-to-end wireless biopotentials recording systems based on off-the-shelf components. Developing and applying circuits, systems and methods, for synchronized largescale monitoring of neural activity, sensory images, and behavior, would produce a dynamic picture of the brain function, which is essential for understanding the brain in action. In this context, we hope that the present thesis become our first step to further contribute to this area