A 32-Channel Time-Multiplexed Artifact-Aware Neural Recording System

This paper presents a low-power, low-noise microsystem for the recording of neural local field potentials or intracranial electroencephalographic signals. It features 32 time-multiplexed channels at the electrode interface and offers the possibility to spatially delta encode data to take advantage of the large correlation of signals captured from nearby channels. The circuit also implements a mixed-signal voltage-triggered auto-ranging algorithm which allows to attenuate large interferers in digital domain while preserving neural information. This effectively increases the system dynamic range and avoids the onset of saturation. A prototype, fabricated in a standard 180 nm CMOS process, has been experimentally verified in-vitro with cellular cultures of primary cortical neurons from mice. The system shows an integrated input-referred noise in the 0.5–200 Hz band of 1.4 µVrms for a spot noise of about 85 nV / √Hz. The system draws 1.5 µW per channel from 1.2 V supply and obtains 71 dB + 26 dB dynamic range when the artifact-aware auto-ranging mechanism is enabled, without penalising other critical specifications such as crosstalk between channels or common-mode and power supply rejection ratios

Anti-artifacts techniques for neural recording front-ends in closed-loop brain-machine interface ICs

In recent years, thanks to the development of integrated circuits, clinical medicine has witnessed significant advancements, enabling more efficient and intelligent treatment approaches. Particularly in the field of neuromedical, the utilization of brain-machine interfaces (BMI) has revolutionized the treatment of neurological diseases such as amyotrophic lateral sclerosis, cerebral palsy, stroke, or spinal cord injury. The BMI acquires neural signals via recording circuits and analyze them to regulate neural stimulator circuits for effective neurological treatment. However, traditional BMI designs, which are often isolated, have given way to closed-loop brain-machine interfaces (CL-BMI) as a contemporary development trend. CL-BMI offers increased integration and accelerated response speed, marking a significant leap forward in neuromedicine. Nonetheless, this advancement comes with its challenges, notably the stimulation artifacts (SA) problem inherent to the structural characteristics of CL-BMI, which poses significant challenges on the neural recording front-ends (NRFE) site. This paper aims to provide a comprehensive overview of technologies addressing artifacts in the NRFE site within CL-BMI. Topics covered will include: (1) understanding and assessing artifacts; (2) exploring the impact of artifacts on traditional neural recording front-ends; (3) reviewing recent technological advancements aimed at addressing artifact-related issues; (4) summarizing and classifying the aforementioned technologies, along with an analysis of future trends

Adv Healthc Mater

A bidirectional brain interface with both "write" and "read" functions can be an important tool for fundamental studies and potential clinical treatments for neurological diseases. Herein, a miniaturized multifunctional fiber-based optoacoustic emitter (mFOE) is reported thatintegrates simultaneous optoacoustic stimulation for "write" and electrophysiology recording of neural circuits for "read". Because of the intrinsic ability of neurons to respond to acoustic wave, there is no requirement of the viral transfection. The orthogonality between optoacoustic waves and electrical field provides a solution to avoid the interference between electrical stimulation and recording. The stimulation function of the mFOE is first validated in cultured ratcortical neurons using calcium imaging. In vivo application of mFOE for successful simultaneous optoacoustic stimulation and electrical recording of brain activities is confirmed in mouse hippocampus in both acute and chronical applications up to 1 month. Minor brain tissue damage is confirmed after these applications. The capability of simultaneous neural stimulation and recording enabled by mFOE opens up new possibilities for the investigation of neural circuits and brings new insights into the study of ultrasound neurostimulation.R21 EY033080/EY/NEI NIH HHSUnited States/S10OD024993/NH/NIH HHSUnited States/R01 NS109794/NS/NINDS NIH HHSUnited States/S10 OD024993/OD/NIH HHSUnited States/CD/ODCDC CDC HHSUnited States/R01 NS123069/NS/NINDS NIH HHSUnited States

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

A 32 Input Multiplexed Channel Analog Front-End with Spatial Delta Encoding Technique and Differential Artifacts Compression

This paper describes a low-noise, low-power and high dynamic range analog front-end intended for sensing neural signals. In order to reduce interface area, a 32-channel multiplexer is implemented on circuit input. Furthermore, a spatial delta encoding is proposed to compress the signal range. A differential artifact compression algorithm is implemented to avoid saturation in the signal path, thus enabling reconstruct or suppressing artifacts in digital domain. The proposed design has been implemented using 0.18 μm TSMC technology. Experimental results shows a power consumption per channel of 1.0 μW, an input referred noise of 1.1 μVrms regarding the bandwidth of interest and a dynamic range of 91 dB.Ministerio de Economía y Competitividad TEC2016-80923-POffice of Naval Research ONR N00014- 19-1-215

Nanotools for Neuroscience and Brain Activity Mapping

Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function

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

3-Dimensional Intracortical Neural Interface For The Study Of Epilepsy

Epilepsy is a chronic disease characterized by recurrent, unprovoked seizures, where seizures are described as storms of uncontrollable neuro-electrical activity within the brain. Seizures are therefore identified by observation of electrical spiking observed through electrical contacts (electrodes) placed on the scalp or the cortex above the epileptic regions. Current epilepsy research is identifying several specific molecular markers that appear at specific layers of the epilepsy-affected cortex. However, technology is limited in allowing for live observation of electrical spiking across these layers. The underlying hypothesis of this project is that electrical interictal activity is generated in a layer- and lateral-specific pattern. This work reports a novel neural probe technology for the manufacturing of 3D arrays of electrodes with integrated microchannels. This new technology is based on a silicon island structure and a simple folding procedure. This method simplifies the assembly or packaging process of 3D neural probes, leading to higher yield and lower cost. Various types of 3D arrays of electrodes, including acute and chronic devices, have been successfully developed. Microchannels have been successfully integrated into the 3D neural probes via isotropic XeF2 gas phase etching and a parylene resealing process. This work describes in detail the development of neural devices targeted towards the study of layer-specific interictal discharges in an animal model of epilepsy. Devices were designed utilizing parameters derived from the rat model of epilepsy. The progression of device design is described from 1st prototype to final chronic device. The fabrication process and potential pitfall are described in detail. Devices have been characterized by SEM (scanning electron microscope) imaging, optical imaging, various types of impedance analysis, and AFM (atomic force microscopy) characterization of the electrode surface. Flow characteristics of the microchannels were also analyzed. Various animal tests have been carried out to demonstrate the recording functionality of the probes, preliminary biocompatibility studies, and the reliability of the final chronic device package. These devices are expected to be of great use to the study of epilepsy as well as various other neurological diseases