A wireless electro-optic platform for multimodal electrophysiology and optogenetics in freely moving rodents

This paper presents the design and the utilization of a wireless electro-optic platform to perform simultaneous multimodal electrophysiological recordings and optogenetic stimulation in freely moving rodents. The developed system can capture neural action potentials (AP), local field potentials (LFP) and electromyography (EMG) signals with up to 32 channels in parallel while providing four optical stimulation channels. The platform is using commercial off-the-shelf components (COTS) and a low-power digital field-programmable gate array (FPGA), to perform digital signal processing to digitally separate in real time the AP, LFP and EMG while performing signal detection and compression for mitigating wireless bandwidth and power consumption limitations. The different signal modalities collected on the 32 channels are time-multiplexed into a single data stream to decrease power consumption and optimize resource utilization. The data reduction strategy is based on signal processing and real-time data compression. Digital filtering, signal detection, and wavelet data compression are used inside the platform to separate the different electrophysiological signal modalities, namely the local field potentials (1–500 Hz), EMG (30–500 Hz), and the action potentials (300–5,000 Hz) and perform data reduction before transmitting the data. The platform achieves a measured data reduction ratio of 7.77 (for a firing rate of 50 AP/second) and weights 4.7 g with a 100-mAh battery, an on/off switch and a protective plastic enclosure. To validate the performance of the platform, we measured distinct electrophysiology signals and performed optogenetics stimulation in vivo in freely moving rondents. We recorded AP and LFP signals with the platform using a 16-microelectrode array implanted in the primary motor cortex of a Long Evans rat, both in anesthetized and freely moving conditions. EMG responses to optogenetic Channelrhodopsin-2 induced activation of motor cortex via optical fiber were also recorded in freely moving rodents

Area- and Energy- Efficient Modular Circuit Architecture for 1,024-Channel Parallel Neural Recording Microsystem.

This research focuses to develop system architectures and associated electronic circuits for a next generation neuroscience research tool, a massive-parallel neural recording system capable of recording 1,024 channels simultaneously. Three interdependent prototypes have been developed to address major challenges in realization of the massive-parallel neural recording microsystems: minimization of energy and area consumption while preserving high quality in recordings. First, a modular 128-channel Δ-ΔΣ AFE using the spectrum shaping has been designed and fabricated to propose an area-and energy efficient solution for neural recording AFEs. The AFE achieved 4.84 fJ/C−s·mm2 figure of merit that is the smallest the area-energy product among the state-of-the-art multichannel neural recording systems. It also features power and area consumption of 3.05 µW and 0.05 mm2 per channel, respectively while exhibiting 63.3 dB signal-to-noise ratio with 3.02 µVrms input referred noise. Second, an on-chip mixed signal neural signal compressor was built to reduce the energy consumption in handling and transmission of the recorded data since this occupies a large portion of the total energy consumption as the number of parallel recording increases. The compressor reduces the data rates of two distinct groups of neural signals that are essential for neuroscience research: LFP and AP without loss of informative signals. As a result, the power consumptions for the data handling and transmissions of the LFP and AP were reduced to about 1/5.35 and 1/10.54 of the uncompressed cases, respectively. In the total data handling and transmission, the measured power consumption per channel is 11.98 µW that is about 1/9 of 107.5 µW without the compression. Third, a compact on-chip dc-to-dc converter with constant 1 MHz switching frequency has been developed to provide reliable power supplies and enhance energy delivery efficiency to the massive-parallel neural recording systems. The dc-to-dc converter has only predictable tones at the output and it exhibits > 80% power conversion efficiency at ultra-light loads, < 100 µW that is relevant power most of the multi-channel neural recording systems consume. The dc-to-dc converter occupies 0.375 mm2 of area which is less than 1/20 of the area the first prototype consumes (8.64 mm2).PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/133244/1/sungyun_1.pd

Nano-Watt Modular Integrated Circuits for Wireless Neural Interface.

In this work, a nano-watt modular neural interface circuit is proposed for ECoG neuroprosthetics. The main purposes of this work are threefold: (1) optimizing the power-performance of the neural interface circuits based on ECoG signal characteristics, (2) equipping a stimulation capability, and (3) providing a modular system solution to expand functionality. To achieve these aims, the proposed system introduces the following contributions/innovations: (1) power-noise optimization based on the ECoG signal driven analysis, (2) extreme low-power analog front-ends, (3) Manchester clock-edge modulation clock data recovery, (4) power-efficient data compression, (5) integrated stimulator with fully programmable waveform, (6) wireless signal transmission through skin, and (7) modular expandable design. Towards these challenges and contributions, three different ECoG neural interface systems, ENI-1, ENI-16, and ENI-32, have been designed, fabricated, and tested. The first ENI system(ENI-1) is a one-channel analog front-end and fabricated in a 0.25µm CMOS process with chopper stabilized pseudo open-loop preamplifier and area-efficient SAR ADC. The measured channel power, noise and area are 1.68µW at 2.5V power-supply, 1.69µVrms (NEF=2.43), and 0.0694mm^2, respectively. The fabricated IC is packaged with customized miniaturized package. In-vivo human EEG is successfully measured with the fabricated ENI-1-IC. To demonstrate a system expandability and wireless link, ENI-16 IC is fabricated in 0.25µm CMOS process and has sixteen channels with a push-pull preamplifier, asynchronous SAR ADC, and intra-skin communication(ISCOM) which is a new way of transmitting the signal through skin. The measured channel power, noise and area are 780nW, 4.26µVrms (NEF=5.2), and 2.88mm^2, respectively. With the fabricated ENI-16-IC, in-vivo epidural ECoG from monkey is successfully measured. As a closed-loop system, ENI-32 focuses on optimizing the power performance based on a bio-signal property and integrating stimulator. ENI-32 is fabricated in 0.18µm CMOS process and has thirty-two recording channels and four stimulation channels with a cyclic preamplifier, data compression, asymmetric wireless transceiver (Tx/Rx). The measured channel power, noise and area are 140nW (680nW including ISCOM), 3.26µVrms (NEF=1.6), and 5.76mm^2, respectively. The ENI-32 achieves an order of magnitude power reduction while maintaining the system performance. The proposed nano-watt ENI-32 can be the first practical wireless closed-loop solution with a practically miniaturized implantable device.PhDElectrical EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/98064/1/schang_1.pd

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

An optogenetic headstage for optical stimulation and neural recording in life science applications

L'optogénétique est une nouvelle méthode de contrôle de l’activité neuronale dans laquelle la lumière est employée pour activer ou arrêter certains neurones. Dans le cadre de ce travail, un dispositif permettant l’acquisition de signaux neuronaux et conduisant à une stimulation optogénétique de façon multicanale et temps-réel a été conçu. Cet outil est muni de deux canaux de stimulation optogénétique et de deux canaux de lecture des signaux neuronaux. La source de lumière est une DEL qui peut consommer jusqu’à 150 milliampères. Les signaux neuronaux acquis sont transmis à un ordinateur par une radio. Les dimensions sont d’environ 20×20×15 mm3 et le poids est de moins de 7 grammes, rendant l’appareil utile pour les expériences sur les petits animaux libres. Selon nos connaissances actuelles, le résultat de ce projet constitue le premier appareil de recherche optogénétique sans-fil, compact offrant la capture de signaux cérébraux et la stimulation optique simultanée.Optogenetics is a new method for controlling the neural activity where light is used to activate or silence, with high spatial and temporal resolution, genetically light-sensitized neurons. In optogenetics, a light source such as a LED, targets light-sensitized neurons. In this work, a light-weight wireless animal optogenetic headstage has been designed that allows multi-channel simultaneous real-time optical stimulation and neural recording. This system has two optogenetic stimulation channels and two electrophysiological reading channels. The optogenetic stimulation channels benefit from high-power LEDs (sinking 150 milliamps) with flexible stimulation patterns and the recorded neural data is wirelessly sent to a computer. The dimensions of the headstage are almost 20×20×15 mm3 and it weighs less than 7 grams. This headstage is suitable for tests on small freely-moving rodents. To the best of our knowledge, this is the first reported fully wireless headstage to offer simultaneous multichannel optical stimulation along with multichannel neural recording capability

Integrated Circuits and Systems for Smart Sensory Applications

Connected intelligent sensing reshapes our society by empowering people with increasing new ways of mutual interactions. As integration technologies keep their scaling roadmap, the horizon of sensory applications is rapidly widening, thanks to myriad light-weight low-power or, in same cases even self-powered, smart devices with high-connectivity capabilities. CMOS integrated circuits technology is the best candidate to supply the required smartness and to pioneer these emerging sensory systems. As a result, new challenges are arising around the design of these integrated circuits and systems for sensory applications in terms of low-power edge computing, power management strategies, low-range wireless communications, integration with sensing devices. In this Special Issue recent advances in application-specific integrated circuits (ASIC) and systems for smart sensory applications in the following five emerging topics: (I) dedicated short-range communications transceivers; (II) digital smart sensors, (III) implantable neural interfaces, (IV) Power Management Strategies in wireless sensor nodes and (V) neuromorphic hardware

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

Analog Signal Buffering and Reconstruction

Wireless sensor networks (WSNs) are capable of a myriad of tasks, from monitoring critical infrastructure such as bridges to monitoring a person\u27s vital signs in biomedical applications. However, their deployment is impractical for many applications due to their limited power budget. Sleep states are one method used to conserve power in resource-constrained systems, but they necessitate a wake-up circuit for detecting unpredictable events. In conventional wake-up-based systems, all information preceding a wake-up event will be forfeited. To avoid this data loss, it is necessary to include a buffer that can record prelude information without sacrificing the power savings garnered by the active use of sleep states.;Unfortunately, traditional memory buffer systems utilize digital electronics which are costly in terms of power. Instead of operating in the target signal\u27s native analog environment, a digital buffer must first expend a great deal of energy to convert the signal into a digital signal. This issue is further compounded by the use of traditional Nyquist sampling which does not adapt to the characteristics of a dynamically changing signal. These characteristics reveal why a digital buffer is not an appropriate choice for a WSN or other resource-constrained system.;This thesis documents the development of an analog pre-processing block that buffers an incoming signal using a new method of sampling. This method requires sampling only local maxima and minima (both amplitude and time), effectively approximating the instantaneous Nyquist rate throughout a time-varying signal. The use of this sampling method along with ultra-low-power analog electronics enables the entire system to operate in the muW power levels. In addition to these power saving techniques, a reconfigurable architecture will be explored as infrastructure for this system. This reconfigurable architecture will also be leveraged to explore wake-up circuits that can be used in parallel with the buffer system

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

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