Implantable Neural Recording System Research Articles

A Reconfigurable, Nonlinear, Low-Power, VCO-Based ADC for Neural Recording Applications

Neural recording systems play a crucial role in comprehending the intricacies of the brain and advancing treatments for neurological disorders. Within these systems, the analog-to-digital converter (ADC) serves as a fundamental component, converting the electrical signals from the brain into digital data that can be further processed and analyzed by computing units. This research introduces a novel nonlinear ADC designed specifically for spike sorting in biomedical applications. Employing MOSFET varactors and voltage-controlled oscillators (VCOs), this ADC exploits the nonlinear capacitance properties of MOSFET varactors, achieving a parabolic quantization function that digitizes the noise with low resolution and the spikes with high resolution, effectively suppressing the background noise present in biomedical signals. This research aims to develop a reconfigurable, nonlinear voltage-controlled oscillator (VCO)-based ADC, specifically designed for implantable neural recording systems used in neuroprosthetics and brain–machine interfaces. The proposed design enhances the signal-to-noise ratio and reduces power consumption, making it more efficient for real-time neural data processing. By improving the performance and energy efficiency of these devices, the research contributes to the development of more reliable medical technologies for monitoring and treating neurological disorders. The quantization step of the ADC spans from 44.8 mV in the low-amplitude range to 1.4 mV in the high-amplitude range. The circuit was designed and simulated utilizing a 180 nm CMOS process; however, no physical prototype has been fabricated at this stage. Post-layout simulations confirm the expected performance. Occupying a silicon area is 0.09 mm2. Operating at a sampling frequency of 16 kS/s and a supply voltage of 1 volt, this ADC consumes 62.4 µW.

Through-polymer, via technology-enabled, flexible, lightweight, and integrated devices for implantable neural probes

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

A compact sub-Hertz local field potential amplifier for implantable biomedical devices

Local field potentials (LFPs) are the ensemble of low frequency neural signals recorded invasively via microelectrodes implanted into brain tissues. The LFP signals acquired by micro-electrodes are very small in amplitude, typically in the range of 1 μV to 0.5 mV, depending on the distance from the electrode and on the size of a cell and contain the signal energy below 1 Hz. These weak signals are required to be amplified by an analog front-end amplifier. In this paper, the design methodology of a local field potential amplifier for an implantable neural recording system is presented. The LFP amplifier is implemented through a low power, low noise front-end instrumentation amplifier. In order to suppress large electrode-induced DC offset voltages, a modified pseudo-resistor is employed in the amplifier’s feedback. The enlarged resistance offered by the pseudo resistor realizes a high-pass cut-off frequency which is well suited for capturing the neural signals occurring in the sub-Hertz frequency range. As a case study, the instrumentation amplifier featuring modified pseudo resistor configured for LFP recording applications is fabricated in a standard 0.18μm CMOS process technology. The measurement results show the proposed LFP amplifier has a low-pass corner frequency of 300 Hz and achieves a high-pass corner frequency of 0.009 Hz with a maximum gain of 37 dB. The LFP circuit fully integrated on-chip occupies an active area of 0.056 mm2 and a power consumption of 1.8 μW from a 1.5-V supply.

A Digitally Assisted Multiplexed Neural Recording System With Dynamic Electrode Offset Cancellation via an LMS Interference-Canceling Filter

This article presents a low-power (LP) area-efficient implantable neural recording system that supports high-density neural implant (HDNI) applications. The system uses a time-division multiple access method to record from 16-neural electrodes simultaneously. A least mean squares (LMSs) algorithm is used to cancel the slowly varying electrode offsets from all channels simultaneously by using a single-tap digital adaptive filter (AF). The presented technique is fabricated in 65-nm CMOS technology and achieves a per-channel area of 0.00248 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ; 68% of which is digital circuitry (and is thus scalable with technology). The overall system consumes 3.38 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{W}$ </tex-math></inline-formula> per channel while achieving 2.6 <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\mu \text{V}_{\mathrm {rms}}$ </tex-math></inline-formula> of input referred noise (IRN) in 10 kHz of bandwidth. The proposed system has a noise efficiency factor (NEF) of 1.83 and is fully integrated on-chip.

Fully Implantable Plantar Cutaneous Augmentation System for Rats Using Closed-loop Electrical Nerve Stimulation.

Plantar cutaneous feedback plays an important role in stable and efficient gait, by modulating the activity of ankle dorsi- and plantar-flexor muscles. However, central and peripheral nervous system trauma often decrease plantar cutaneous feedback and/or interneuronal excitability in processing the plantar cutaneous feedback. In this study, we tested a fully implantable neural recording and stimulation system augmenting plantar cutaneous feedback. Electromyograms were recorded from the medial gastrocnemius muscle for stance phase detection, while biphasic stimulation pulses were applied to the distal-tibial nerve during the stance phase to augment plantar cutaneous feedback. A Bluetooth low energy and a Qi-standard inductive link were adopted for wireless communication and wireless charging, respectively. To test the operation of the system, one intact rat walked on a treadmill with the electrical system implanted into its back. Leg kinematics were recorded to identify the stance phase. Stimulation was applied, with a 250-ms onset delay from stance onset and 200-ms duration, resulting in the onset at 47.58±2.82% of stance phase and the offset at 83.49±4.26% of stance phase (Mean±SEM). The conduction velocity of the compound action potential (31.2 m/s and 41.6 m/s at 1·T and 2·T, respectively) suggests that the evoked action potential was characteristic of an afferent volley for cutaneous feedback. We also demonstrated successful wireless charging and system reset functions. The experimental results suggest that the presented implantable system can be a valuable neural interface tool to investigate the effect of plantar cutaneous augmentation on gait in a rat model.

A 10-Bit 120 kS/s SAR ADC Without Reset Energy for Biomedical Electronics

A 10-bit 120 kS/s successive-approximation-register analog-to-digital converter (SAR ADC) is realized for implantable multichannel neural recording system. In order to reduce power consumption and area occupation, an improved energy-efficient VCM-based switching scheme is proposed. Different from the monotonic switching scheme, the switching procedure for each bit cycle of this proposed scheme is almost symmetrical, which facilitates the comparator design. Additionally, since all these capacitors are connected to VCM in the sampling phase, the reset energy of this switching scheme is zero. Bootstrapped sampling switches are employed for linearity improvement. Realized in 0.18-µm CMOS, the proposed ADC occupies an active area of 0.13 mm2. Including the I/O and two 4-to-1 multiplexers, the power consumption is 2.97 µW at 120 kS/s sampling rate. The figure-of-merit of this proposed SAR ADC is about 36.9 fJ/conversion-step.

An Implantable Peripheral Nerve Recording and Stimulation System for Experiments on Freely Moving Animal Subjects

A new study with rat sciatic nerve model for peripheral nerve interfacing is presented using a fully-implanted inductively-powered recording and stimulation system in a wirelessly-powered standard homecage that allows animal subjects move freely within the homecage. The Wireless Implantable Neural Recording and Stimulation (WINeRS) system offers 32-channel peripheral nerve recording and 4-channel current-controlled stimulation capabilities in a 3 × 1.5 × 0.5 cm3 package. A bi-directional data link is established by on-off keying pulse-position modulation (OOK-PPM) in near field for narrow-band downlink and 433 MHz OOK for wideband uplink. An external wideband receiver is designed by adopting a commercial software defined radio (SDR) for a robust wideband data acquisition on a PC. The WINeRS-8 prototypes in two forms of battery-powered headstage and wirelessly-powered implant are validated in vivo, and compared with a commercial system. In the animal study, evoked compound action potentials were recorded to verify the stimulation and recording capabilities of the WINeRS-8 system with 32-ch penetrating and 4-ch cuff electrodes on the sciatic nerve of awake freely-behaving rats. Compared to the conventional battery-powered system, WINeRS can be used in closed-loop recording and stimulation experiments over extended periods without adding the burden of carrying batteries on the animal subject or interrupting the experiment.

A novel adaptive real-time detection algorithm for an area-efficient CMOS spike detector circuit

For implantable neural detection and recording systems, computationally simple methods are preferred over complex algorithms for power efficiency. Amplitude threshold is the simplest and the most widely employed method for neural spike detection. However, this conventional method for setting the threshold is sensitive to the spike firing rate and spike amplitude. In this work, a novel approach is described for a real-time calculation of the detection threshold in a way that is robust to the change in spike firing rate as well as spike amplitude. An algorithm is proposed that adaptively sets the threshold from background activity by approximating the nonlinear energy operator (NEO). The detection method can distinguish neural spikes accurately with firing rate greater than 100 Hz. The spike detector circuit dissipates 5.1 μW of power per channel and occupies 0.018 mm2 of layout area when implemented in 0.18 μm CMOS process.

A Hardware-Efficient Scalable Spike Sorting Neural Signal Processor Module for Implantable High-Channel-Count Brain Machine Interfaces.

Next-generation brain machine interfaces demand a high-channel-count neural recording system to wirelessly monitor activities of thousands of neurons. A hardware efficient neural signal processor (NSP) is greatly desirable to ease the data bandwidth bottleneck for a fully implantable wireless neural recording system. This paper demonstrates a complete multichannel spike sorting NSP module that incorporates all of the necessary spike detector, feature extractor, and spike classifier blocks. To meet high-channel-count and implantability demands, each block was designed to be highly hardware efficient and scalable while sharing resources efficiently among multiple channels. To process multiple channels in parallel, scalability analysis was performed, and the utilization of each block was optimized according to its input data statistics and the power, area and/or speed of each block. Based on this analysis, a prototype 32-channel spike sorting NSP scalable module was designed and tested on an FPGA using synthesized datasets over a wide range of signal to noise ratios. The design was mapped to 130nm CMOS to achieve 0.75μW power and 0.023mm2 area consumptions per channel based on post synthesis simulation results, which permits scalability of digital processing to 690 channels on a 4×4 mm2 electrode array.

Toward a distributed free-floating wireless implantable neural recording system.

To understand the complex correlations between neural networks across different regions in the brain and their functions at high spatiotemporal resolution, a tool is needed for obtaining long-term single unit activity (SUA) across the entire brain area. The concept and preliminary design of a distributed free-floating wireless implantable neural recording (FF-WINeR) system are presented, which can enabling SUA acquisition by dispersedly implanting tens to hundreds of untethered 1 mm3 neural recording probes, floating with the brain and operating wirelessly across the cortical surface. For powering FF-WINeR probes, a 3-coil link with an intermediate high-Q resonator provides a minimum S21 of -22.22 dB (in the body medium) and -21.23 dB (in air) at 2.8 cm coil separation, which translates to 0.76%/759 μW and 0.6%/604 μW of power transfer efficiency (PTE) / power delivered to a 9 kΩ load (PDL), in body and air, respectively. A mock-up FF-WINeR is implemented to explore microassembly method of the 1×1 mm2 micromachined silicon die with a bonding wire-wound coil and a tungsten micro-wire electrode. Circuit design methods to fit the active circuitry in only 0.96 mm2 of die area in a 130 nm standard CMOS process, and satisfy the strict power and performance requirements (in simulations) are discussed.

Design and evaluation of area-efficient and wide-range impedance analysis circuit for multichannel high-quality brain signal recording system

To enable chronic and stable neural recording, we have been developing an implantable multichannel neural recording system with impedance analysis functions. One of the important things for high-quality neural signal recording is to maintain well interfaces between recording electrodes and tissues. We have proposed an impedance analysis circuit with a very small circuit area, which is implemented in a multichannel neural recording and stimulating system. In this paper, we focused on the design of an impedance analysis circuit configuration and the evaluation of a minimal voltage measurement unit. The proposed circuit has a very small circuit area of 0.23 mm2 designed with 0.18 µm CMOS technology and can measure interface impedances between recording electrodes and tissues in ultrawide ranges from 100 Ω to 10 MΩ. In addition, we also successfully acquired interface impedances using the proposed circuit in agarose gel experiments.

Adaptive Threshold Neural Spike Detector Using Stationary Wavelet Transform in CMOS.

Spike detection is an essential first step in the analysis of neural recordings. Detection at the frontend eases the bandwidth requirement for wireless data transfer of multichannel recordings to extra-cranial processing units. In this work, a low power digital integrated spike detector based on the lifting stationary wavelet transform is presented and developed. By monitoring the standard deviation of wavelet coefficients, the proposed detector can adaptively set a threshold value online for each channel independently without requiring user intervention. A prototype 16-channel spike detector was designed and tested in an FPGA. The method enables spike detection with nearly 90% accuracy even when the signal-to-noise ratio is as low as 2. The design was mapped to 130 nm CMOS technology and shown to occupy 0.014 mm(2) of area and dissipate 1.7 μW of power per channel, making it suitable for implantable multichannel neural recording systems.

A 700mV low power low noise implantable neural recording system design.

A low power, low noise implantable neural recording interface for use in a Radio-Frequency Identification (RFID) is presented in this paper. A two stage neural amplifier and 8 bit Pipelined Analog to Digital Converter (ADC) are integrated in this system. The optimized number of amplifier stages demonstrates the minimum power and area consumption; The ADC utilizes a novel offset cancellation technique robust to device leakage to reduce the input offset voltage. The neural amplifier and ADC both utilize 700mV power supply. The midband gain of neural amplifier is 58.4dB with a 3dB bandwidth from 0.71 to 8.26 kHz. Measured input-referred noise and total power consumption are 20.7μVrms and 1.90 respectively. The ADC achieves 8 bit accuracy at 16Ksps with an input voltage of ±400mV. Combined simulation and measurement results demonstrate the neural recording interface's suitability for in situ neutral activity recording.

A 100-Channel Hermetically Sealed Implantable Device for Chronic Wireless Neurosensing Applications

A 100-channel fully implantable wireless broadband neural recording system was developed. It features 100 parallel broadband (0.1 Hz-7.8 kHz) neural recording channels, a medical grade 200 mAh Li-ion battery recharged inductively at 150 kHz , and data telemetry using 3.2 GHz to 3.8 GHz FSK modulated wireless link for 48 Mbps Manchester encoded data. All active electronics are hermetically sealed in a titanium enclosure with a sapphire window for electromagnetic transparency. A custom, high-density configuration of 100 individual hermetic feedthrough pins enable connection to an intracortical neural recording microelectrode array. A 100 MHz bandwidth custom receiver was built to remotely receive the FSK signal and achieved -77.7 dBm sensitivity with 10(-8) BER at 48 Mbps data rate. ESD testing on all the electronic inputs and outputs has proven that the implantable device satisfies the HBM Class-1B ESD Standard. In addition, the evaluation of the worst-case charge density delivered to the tissue from each I/O pin verifies the patient safety of the device in the event of failure. Finally, the functionality and reliability of the complete device has been tested on-bench and further validated chronically in ongoing freely moving swine and monkey animal trials for more than one year to date.

A Wideband Dual-Antenna Receiver for Wireless Recording From Animals Behaving in Large Arenas

A low-noise wideband receiver (Rx) is presented for a multichannel wireless implantable neural recording (WINeR) system that utilizes time-division multiplexing of pulse width modulated (PWM) samples. The WINeR-6 Rx consists of four parts: 1) RF front end; 2) signal conditioning; 3) analog output (AO); and 4) field-programmable gate array (FPGA) back end. The RF front end receives RF-modulated neural signals in the 403-490MHz band with a wide bandwidth of 18MHz. The frequency-shift keying (FSK) PWM demodulator in the FPGA is a time-to-digital converter with 304ps resolution, which converts the analog pulse width information to 16-bit digital samples. Automated frequency tracking has been implemented in the Rx to lock onto the free-running voltage-controlled oscillator in the transmitter (Tx). Two antennas and two parallel RF paths are used to increase the wireless coverage area. BCI-2000 graphical user interface has been adopted and modified to acquire, visualize, and record the recovered neural signals in real time. The AO module picks three demultiplexed channels and converts them into analog signals for direct observation on an oscilloscope. One of these signals is further amplified to generate an audio output, offering users the ability to listen to ongoing neural activity. Bench-top testing of the Rx performance with a 32-channel WINeR-6 Tx showed that the input referred noise of the entire system at a Tx-Rx distance of 1.5m was 4.58μV rms with 8-bit resolution at 640 kSps. In an in vivo experiment, location-specific receptive fields of hippocampal place cells were mapped during a behavioral experiment in which a rat completed 40 laps in a large circular track. Results were compared against those acquired from the same animal and the same set of electrodes by a commercial hardwired recording system to validate the wirelessly recorded signals.

CMOS implementation of a low-power BPSK demodulator for wireless implantable neural command transmission

A new BPSK demodulator was presented. By using a clock multiplier with very simple circuit structure to replace the analog multiplier in the traditional BPSK demodulator, the circuit structure of the demodulator became simpler and hence its power consumption became lower. Simpler structure and lower power will make the designed demodulator more suitable for use in an internal single chip design for a wireless implantable neural recording system. The proposed BPSK demodulator was implemented by Global Foundries 0.35 μm CMOS technology with a 3.3 V power supply. The designed chip area is only 0.07 mm2 and the power consumption is 0.5 mW. The test results show that it can work correctly.

Low-Power, High Data Rate Transceiver System for Implantable Prostheses

Wireless telemetry is crucial for long-term implantable neural recording systems. RF-encoded neurological signals often require high data-rates to transmit information from multiple electrodes with a sufficient sampling frequency and resolution. In this work, we quantify the effects of interferers and tissue attenuation on a wireless link for optimal design of future systems. The wireless link consists of an external receiver capable of demodulating FSK/OOK transmission at speeds up to 8 Mbps, with <1e-5 bit-error rate (BER) without error correction, and a fully implanted transmitter consuming about 1.05 mW. The external receiver is tested with the transmitter in vivo to show demodulation efficacy of the transcutaneous link at high data-rates. Transmitter/Receiver link BER is quantified in typical and controlled RF environments for ex vivo and in vivo performance.

Development of Si Double-Sided Microelectrode for Platform of Brain Signal Processing System

We have proposed a new implantable neural recording system, which we call the brain signal processing system (BSPS). In this system, LSI chips such as amplifiers, analog-to-digital converters, and multiplexers are integrated on the Si microelectrode array. To analyze the brain functions or to develop medical treatments for brain disorders, a high-density recording of action potentials is strongly required. To realize high-density recording of action potentials, we propose a novel Si double-sided microelectrode that has recording sites on both front and back sides. The back-side recording sites are connected to a recording apparatus by wire bonding through Si via holes. We fabricated the carefully designed Si double-sided microelectrode and evaluated the electrical characteristics of the Si microelectrode. The front- and back-side recording sites had impedance values of 2.5 and 2.7 MΩ at 1 kHz, respectively, which indicated that both recording sites have equivalent characteristics. An in vitro experiment of neuronal action potential recording using the fabricated Si double-sided microelectrode was performed. The CA1 areas of 400-µm-thick hippocampal slices obtained from the brains of guinea pigs were employed, and we successfully recorded neuronal action potentials from the recording sites of both sides.

Extracting Electric Power From Human Body For Supplying Neural Recording System

Abstract A powerful approach to the characterization of cellular electrical activity is electrical recording from cells or living tissues. The human central and / or peripheral nervous system has been a subject of study and fascination of the neuroscience and biomedical engineering communities for many decades. In this paper, we propose a new approach to feed implantable neural recording system, which based on extracting electrical power from human tissue warmth in order to supply a biomedical neural recording system. The major issue to overcome, in the design of a system that is aimed at being implant into the human body, is having a low power consumption, low noise circuit and small dimension to minimize tissue damage.

A wireless implantable multichannel digital neural recording system for a micromachined sieve electrode

This paper reports the development of an implantable, fully integrated, multichannel peripheral neural recording system, which is powered and controlled using an RF telemetry link. The system allows recording of /spl plusmn/500 /spl mu/V neural signals from axons regenerated through a micromachined silicon sieve electrode. These signals are amplified using on-chip 100 Hz to 3.1 kHz bandlimited amplifiers, multiplexed, and digitized with a low-power (<2 mW), moderate speed (8 /spl mu/s/b) current-mode 8-b analog-to-digital converter (ADC). The digitized signal is transmitted to the outside world using a passive RF telemetry link. The circuit is implemented using a bipolar CMOS process. The signal processing CMOS circuitry dissipates only 10 mW of power from a 5-V supply while operating at 2 MHz and consumes 4/spl times/4 mm/sup 2/ of area. The overall circuit including the RF interface circuitry contains over 5000 transistors, dissipates 90 mW of power, and consumes 4/spl times/6 mm/sup 2/ of area.