An Analog Front End for Recording Neuronal Activity in Freely Behaving Small Animals

Extracting characteristic brain signals and simultaneous recording animals behaving could help us to understand the complex behavior of neuronal ensembles. Here, a system was established to record local field potentials (LFP) and extracellular signal or multiple-unit discharge and behavior synchronously by utilizing electrophysiology and integrated circuit technique. It comprised microelectrodes and micro-driver assembly, analog front end (AFE),while a computer (Pentium III ) was used as the platform for the graphic user interface, which was developed using the LabVIEW programming language. It was designed as a part of ongoing research to develop a portable wireless neural signal recording system. We believe that this information will be useful for the research of brain-computer interface.

A multi-channel fully differential programmable integrated circuit for neural recording application

A multi-channel, fully differential programmable chip for neural recording application is presented. The integrated circuit incorporates eight neural recording amplifiers with tunable bandwidth and gain, eight 4thorder Bessel switch capacitor filters, an 8-to-1 analog time-division multiplexer, a fully differential successive approximation register analog-to-digital converter （SAR ADC）, and a serial peripheral interface for communication. The neural recording amplifier presents a programmable gain from 53 dB to 68 dB, a tunable low cut-off frequency from 0.1 Hz to 300 Hz, and 3.77μVrms input-referred noise over a 5 kHz bandwidth. The SAR ADC digitizes signals at maximum sampling rate of 20 μS/s per channel and achieves an ENOB of 7.4. The integrated circuit is designed and fabricated in 0.18-μm CMOS mix-signal process. We successfully performed a multi-channel in-vivo recording experiment from a rat cortex using the neural recording chip.

A CMOS frontend chip for implantable neural recording with wide voltage supply range

A design for a CMOS frontend integrated circuit （chip） for neural signal acquisition working at wide voltage supply range is presented in this paper. The chip consists of a preamplifier, a serial instrumental amplifier （IA） and a cyclic analog-to-digital converter （CADC）. The capacitive-coupled and capacitive-feedback topology combined with MOS-bipolar pseudo-resistor element is adopted in the preamplifier to create a -3 dB upper cut-off frequency less than 1 Hz without using a ponderous discrete device. A dual-amplifier instrumental amplifier is used to provide a low output impedance interface for ADC as well as to boost the gain. The preamplifier and the serial instrumental amplifier together provide a midband gain of 45.8 dB and have an input-referred noise of 6.7 μVrms integrated from 1 Hz to 5 kHz. The ADC digitizes the amplified signal at 12-bits precision with a highest sampling rate of 130 kS/s. The measured effective number of bits （ENOB） of the ADC is 8.7 bits. The entire circuit draws 165 to 216 μA current from the supply voltage varied from 1.34 to 3.3 V. The prototype chip is fabricated in the 0.18-μm CMOS process and occupies an area of 1.23 mm2 （including pads）. In-vitro recording was successfully carried out by the proposed frontend chip.

A compact neural recording interface based on silicon microelectrode

A prototype of hybrid neural recording interface has been developed for extracellular neural recording. It consists of a silicon-based plane microelectrode array and a CMOS low noise neural amplifier chip. The neural amplifier chip is designed and implemented in 0.18 μm N-well CMOS 1P6M technology. The area of the neural preamplifier is only 0.042 mm2 with a gain of 48.3 dB. The input equivalent noise is 4.73 btVrms within pass bands of 4 kHz. To avoid cable tethering for high dense mul- tichannel neural recording interface and make it compact, flip-chip bonding is used to integrate the preamplifier chip and the microelectrode together. The hybrid device measures 3 mm×5.5 mm×330μm, which is convenient for implant or in-vivo neu- ral recording. The hybrid device was testified in in-vivo experiment. Neural signals were recorded from hippocampus region of anesthetized Sprague Dawley rats successfully.

A multi-channel analog IC for in vitro neural recording

Recent work in the field ofneurophysiology has demonstrated that, by observing the firing characteristic of action potentials （AP） and the exchange pattern of signals between neurons, it is possible to reveal the nature of ＂memory＂ and ＂thinking＂ and help humans to understand how the brain works. To address these needs, we developed a prototype fully integrated circuit （IC） with micro-electrode array （MEA） for neural recording. In this scheme, the microelectrode array is composed by 64 detection electrodes and 2 reference electrodes. The proposed IC consists of 8 recording channels with an area of 5 x 5 mm2. Each channel can operate independently to process the neural signal by amplifying, filtering, etc. The chip is fabricated in 0.5-#m CMOS technology. The simulated and measured results show the system provides an effective device for recording feeble signal such as neural signals.

Towards high-density recording of brain-wide neural activity

Brain activity is highly structured within local microcircuits and brain-wide networks,involving exquisite coordination across multiple brain regions in both superficial and deep structures^([1]).To understand how brain represents,transforms and communicates in-

Nano functional neural interfaces

Engineered functional neural interfaces （fNIs） serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.

MouseVenue3D:A Markerless Three-Dimension Behavioral Tracking System for Matching Two-Photon Brain Imaging in Free-Moving Mice

Understanding the connection between brain and behavior in animals requires precise monitoring of their behaviors in three-dimensional(3-D)space.However,there is no available three-dimensional behavior capture system that focuses on rodents.Here,we present MouseVenue3D,an automated and low-cost system for the efficient capture of 3-D skeleton trajectories in markerless rodents.We improved the most time-consuming step in 3-D behavior capturing by developing an automatic calibration module.Then,we validated this process in behavior recognition tasks,and showed that 3-D behavioral data achieved higher accuracy than 2-D data.Subsequently,MouseVenue3D was combined with fast high-resolution miniature two-photon microscopy for synchronous neural recording and behavioral tracking in the freely-moving mouse.Finally,we successfully decoded spontaneous neuronal activity from the 3-D behavior of mice.Our findings reveal that subtle,spontaneous behavior modules are strongly correlated with spontaneous neuronal activity patterns.

Recent advances in electronic devices for monitoring and modulation of brain

The brain is actuated by billions of neurons with trillions of interconnections that regulate human behaviors.Understanding the mechanisms of these systems that induce sensory reactions and respond to disease remains one of the greatest challenges in science,engineering,and medicine.Recent advances in nanomaterials and nanotechnologies have led to the extensive research of electronic devices for brain interfaces to better understand the neural activities of the brains complex nervous system.The development of sensor devices for monitoring the physiological signals of the brain related to traumatic injury status has accompanied by the progress of electronic neural probes in parallel.In addition,these neurological and stereotactic surgical revolutions hold immense potential for clinical analysis of pharmacological systems within cerebral tissues.Here,we review the progress of electronic devices interfacing with brain in terms of the materials,fabrication technologies,and device designs.Neurophysiological activity can be measured and modulated by brain probes based on newly developed nanofabrication methodologies.Furthermore,in vivo pathological monitoring of the brain and pharmacological assessment has been developed in miniaturized and wireless form.We also consider the key challenges and prospects for further development,and explore the future directions emerging in the latest research.