Elliot Greenwald

A VLSI Neural Monitoring System With Ultra-Wideband Telemetry for Awake Behaving Subjects

Long term monitoring of neuronal activity in awake behaving subjects can provide fundamental information about brain dynamics for both neuroscience and neuroengineering applications. Recent advances in VLSI systems has focused on designing wireless neural recording systems which can be mounted on animals and acquire neural signals in real time. These advances provide an unparalleled opportunity to study phenomenon such as neural plasticity in both a basic science setting (learning and memory), and also a clinical setting (injury and recovery). Here we present an integrated VLSI system for wireless telemetry of the entire spectrum of neural signals, spikes, local field potentials, electrocorticograms (ECoG) and electroencephalograms (EEG). The system integrates two custom designed VLSI chips, a 16 channel neural interface which can amplify, filter and digitize neural data up to 16 kS/sec and 12 bits and a low power ultra-wideband (UWB) chip which can transmit data at rates up to 14 Mbps. The entire system which includes these VLSI circuits, a digital interface board and a battery, is small, 1.2×1.2×2.6 in3, and light weight, 33 grams, so it can be chronically mounted on a rat. The system consumes 32.8 mA at 3.3V and can record for 6 hours running from the 200 mAh coin cell battery. Bench-top and in vitro characterization of the system showed comparable performance to the wired recording system.

Implantable neurotechnologies: bidirectional neural interfaces—applications and VLSI circuit implementations

Abstract A bidirectional neural interface is a device that transfers information into and out of the nervous system. This class of devices has potential to improve treatment and therapy in several patient populations. Progress in very large-scale integration has advanced the design of complex integrated circuits. System-on-chip devices are capable of recording neural electrical activity and altering natural activity with electrical stimulation. Often, these devices include wireless powering and telemetry functions. This review presents the state of the art of bidirectional circuits as applied to neuroprosthetic, neurorepair, and neurotherapeutic systems.

Implantable neurotechnologies: a review of integrated circuit neural amplifiers

Neural signal recording is critical in modern day neuroscience research and emerging neural prosthesis programs. Neural recording requires the use of precise, low-noise amplifier systems to acquire and condition the weak neural signals that are transduced through electrode interfaces. Neural amplifiers and amplifier-based systems are available commercially or can be designed in-house and fabricated using integrated circuit (IC) technologies, resulting in very large-scale integration or application-specific integrated circuit solutions. IC-based neural amplifiers are now used to acquire untethered/portable neural recordings, as they meet the requirements of a miniaturized form factor, light weight and low power consumption. Furthermore, such miniaturized and low-power IC neural amplifiers are now being used in emerging implantable neural prosthesis technologies. This review focuses on neural amplifier-based devices and is presented in two interrelated parts. First, neural signal recording is reviewed, and practical challenges are highlighted. Current amplifier designs with increased functionality and performance and without penalties in chip size and power are featured. Second, applications of IC-based neural amplifiers in basic science experiments (e.g., cortical studies using animal models), neural prostheses (e.g., brain/nerve machine interfaces) and treatment of neuronal diseases (e.g., DBS for treatment of epilepsy) are highlighted. The review concludes with future outlooks of this technology and important challenges with regard to neural signal amplification.

A VLSI neural monitoring system with ultra-wideband telemetry for awake behaving subjects

Long-term monitoring of neuronal activity in awake behaving subjects can provide fundamental information about brain dynamics for neuroscience and neuroengineering applications. Here, we present a miniature, lightweight, and low-power recording system for monitoring neural activity in awake behaving animals. The system integrates two custom designed very-large-scale integrated chips, a neural interface module fabricated in 0.5 μm complementary metal-oxide semiconductor technology and an ultra-wideband transmitter module fabricated in a 0.5 μm silicon-on-sapphire (SOS) technology. The system amplifies, filters, digitizes, and transmits 16 channels of neural data at a rate of 1 Mb/s. The entire system, which includes the VLSI circuits, a digital interface board, a battery, and a custom housing, is small and lightweight (24 g) and, thus, can be chronically mounted on small animals. The system consumes 4.8 mA and records continuously for up to 40 h powered by a 3.7-V, 200-mAh rechargeable lithium-ion battery. Experimental benchtop characterizations as well as in vivo multichannel neural recordings from awake behaving rats are presented here.

A CMOS neurostimulator with on-chip DAC calibration and charge balancing

A multi-channel biphasic neural stimulator with on-chip DAC calibration and current matching capabilities is presented. Each channel consists of two sub-binary radix DACs, for the anodic and cathodic stimulation phases, and a wideswing high output impedance current source and sink. A single integrator is shared among channels and serves to calibrate DAC coefficients and to closely match the anodic and cathodic stimulation phases. After calibration, the differential non-linearity is bounded between +/- 0.5 LSBs at 8-bit resolution, and the two stimulation phases can be matched to better than 50 nA. We demonstrate operation with stimulation through a tungsten microelectrode in saline, and show stimulator induced modulation of neural activity in the cortex of a rat. Our novel architecture allows for blind self-calibration, amenable to implantable neural interfaces.

Design and characterization of a miniaturized epi-illuminated microscope

The ability to observe functional and morphological changes in the brain is critical in understanding behavioral and developmental neuroscience. With advances in electronics and miniaturization, electrophysiological recordings from awake, behaving animals has allowed investigators to perform a multitude of behavioral studies by observing changes as an animal is engaged in certain tasks. Imaging offers advantages of observing structure as well as function, and the ability to monitor activity over large areas. However, imaging from an awake, behaving animal has not been explored well. We present the design and characterization of a miniaturized epi-illuminated optical system that is part of a larger goal to perform optical imaging in awake, behaving animals. The system comprises of a tunable light source and imaging optics in a small footprint of 18 mm diameter, 18 mm height and weight 5.7 grams. It offers a spatial illumination non-uniformity of 3.2% over a maximum field of view of 1.5 mm × 1.5 mm, negligible temporal illumination and temperature variation and controllable magnification. Uncorrected radial distortion was 5.3% (corrected to 1.8%) and the spatial frequency response was comparable to a reference system. The system was used to image cortical vasculature in an anesthetized rat.

A CMOS Current Steering Neurostimulation Array With Integrated DAC Calibration and Charge Balancing

An 8-channel current steerable, multi-phasic neural stimulator with on-chip current DAC calibration and residue nulling for precise charge balancing is presented. Each channel consists of two sub-binary radix DACs followed by wide-swing, high output impedance current buffers providing time-multiplexed source and sink outputs for anodic and cathodic stimulation. A single integrator is shared among channels and serves to calibrate DAC coefficients and to closely match the anodic and cathodic stimulation phases. Following calibration, the differential non-linearity is within

Intranasal post-cardiac arrest treatment with orexin-A facilitates arousal from coma and ameliorates neuroinflammation

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A Bidirectional Neural Interface IC With Chopper Stabilized BioADC Array and Charge Balanced Stimulator

LSB at 8-bit resolution, and the two stimulation phases are matched within 0.3%. Individual control in digital programming of stimulation coefficients across the array allows altering the spatial profile of current stimulation for selection of stimulation targets by current steering. Combined with the self-calibration and current matching functions, the current steering capabilities integrated on-chip support use in fully implanted neural interfaces with autonomous operation for and adaptive stimulation under variations in electrode and tissue conditions. As a proof-of-concept we applied current steering stimulation through a multi-channel cuff electrode on the sciatic nerve of a rat.

VLSI circuits for bidirectional interface to peripheral and visceral nerves

Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Significant subsequent morbidity and mortality in post-CA patients are largely due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia post-CA syndrome (PCAS). PCAS results in strong inflammatory responses including neuroinflammation response leading to poor outcome. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches to promote cortical or cognitive arousal following successful return of spontaneous circulation (ROSC). Hypothalamic orexinergic pathway is responsible for arousal and it is negatively affected by neuroinflammation. However, whether activation of the orexinergic pathway can curtail neuroinflammation is unknown. We hypothesize that targeting the orexinergic pathway via intranasal orexin-A (ORXA) treatment will enhance arousal from coma and decrease the production of proinflammatory cytokines resulting in improved functional outcome after resuscitation. We used a highly validated CA rat model to determine the effects of intranasal ORXA treatment 30-minute post resuscitation. At 4hrs post-CA, the mRNA levels of proinflammatory markers (IL1β, iNOS, TNF-α, GFAP, CD11b) and orexin receptors (ORX1R and ORX2R) were examined in different brain regions. CA dramatically increased proinflammatory markers in all brain regions particularly in the prefrontal cortex, hippocampus and hypothalamus. Post-CA intranasal ORXA treatment significantly ameliorated the CA-induced neuroinflammatory markers in the hypothalamus. ORXA administration increased production of orexin receptors (ORX1R and ORX2R) particularly in hypothalamus. In addition, ORXA also resulted in early arousal as measured by quantitative electroencephalogram (EEG) markers, and recovery of the associated behavioral neurologic deficit scale score (NDS). Our results indicate that intranasal delivery of ORXA post-CA has an anti-inflammatory effect and accelerates cortical EEG and behavioral recovery. Beneficial outcomes from intranasal ORXA treatment lay the groundwork for therapeutic clinical approach to treating post-CA coma.