Gian Nicola Angotzi

Carbon nanotube composite coating of neural microelectrodes preferentially improves the multiunit signal-to-noise ratio

Extracellular metal microelectrodes are widely used to record single neuron activity in vivo. However, their signal-to-noise ratio (SNR) is often far from optimal due to their high impedance value. It has been recently reported that carbon nanotube (CNT) coatings may decrease microelectrode impedance, thus improving their performance. To tease out the different contributions to SNR of CNT-coated microelectrodes we carried out impedance and noise spectroscopy measurements of platinum/tungsten microelectrodes coated with a polypyrrole-CNT composite. Neuronal signals were recorded in vivo from rat cortex by employing tetrodes with two recording sites coated with polypyrrole-CNT and the remaining two left untreated. We found that polypyrrole-CNT coating significantly reduced the microelectrode impedance at all neuronal signal frequencies (from 1 to 10 000 Hz) and induced a significant improvement of the SNR, up to fourfold on average, in the 150-1500 Hz frequency range, largely corresponding to the multiunit frequency band. An equivalent circuit, previously proposed for porous conducting polymer coatings, reproduced the impedance spectra of our coated electrodes but could not explain the frequency dependence of SNR improvement following polypyrrole-CNT coating. This implies that neither the neural signal amplitude, as recorded by a CNT-coated metal microelectrode, nor noise can be fully described by the equivalent circuit model we used here and suggests that a more detailed approach may be needed to better understand the signal propagation at the electrode-solution interface. Finally, the presence of significant noise components that are neither thermal nor electronic makes it difficult to establish a direct relationship between the actual electrode noise and the impedance spectra.

Peripheral Neural Activity Recording and Stimulation System

This paper presents a portable, embedded, microcontroller-based system for bidirectional communication (recording and stimulation) between an electrode, implanted in the peripheral nervous system, and a host computer. The device is able to record and digitize spontaneous and/or evoked neural activities and store them in data files on a PC. In addition, the system has the capability of providing electrical stimulation of peripheral nerves, injecting biphasic current pulses with programmable duration, intensity, and frequency. The recording system provides a highly selective band-pass filter from 800 Hz to 3 kHz, with a gain of 56 dB. The amplification range can be further extended to 96 dB with a variable gain amplifier. The proposed acquisition/stimulation circuitry has been successfully tested through in vivo measurements, implanting a tf-LIFE electrode in the sciatic nerve of a rat. Once implanted, the device showed an input referred noise of 0.83 μVrms, was capable of recording signals below 10 μ V, and generated muscle responses to injected stimuli. The results demonstrate the capability of processing and transmitting neural signals with very low distortion and with a power consumption lower than 1 W. A graphic, user-friendly interface has been developed to facilitate the configuration of the entire system, providing the possibility to activate stimulation and monitor recordings in real time.

Biologically compatible neural interface to safely couple nanocoated electrodes to the surface of the brain.

The ongoing interest in densely packed miniaturized electrode arrays for high-resolution epicortical recordings has induced many researchers to explore the use of nanomaterial coatings to reduce electrode impedance while increasing signal-to-noise ratio and charge injection capability. Although these materials are very effective, their use in clinical practice is strongly inhibited by concerns about the potential risks derived from the use of nanomaterials in direct contact with the human brain. In this work we propose a novel approach to safely couple nanocoated electrodes to the brain surface by encapsulating them with a biocompatible hydrogel. We prove that fibrin hydrogel coating over nanocoated high-density arrays of epicortical microelectrodes is electrically transparent and allows avoiding direct exposure of the brain tissue to the nanocoatings while maintaining all the advantages derived from the nanostructured electrode surface. This method may make available acute and sub-acute neural recordings with nanocoated high-resolution arrays for clinical applications.

PEDOT-CNT-Coated Low-Impedance, Ultra-Flexible, and Brain-Conformable Micro-ECoG Arrays

Electrocorticography (ECoG) is becoming a common tool for clinical applications, such as preparing patients for epilepsy surgery or localizing tumor boundaries, as it successfully balances invasiveness and information quality. Clinical ECoG arrays use millimeter-scale electrodes and centimeter-scale pitch and cannot precisely map neural activity. Higher-resolution electrodes are of interest for both current clinical applications, providing access to more precise neural activity localization and novel applications, such as neural prosthetics, where current information density and spatial resolution is insufficient to suitably decode signals for a chronic brain-machine interface. Developing such electrodes is not trivial because their small contact area increases the electrode impedance, which seriously affects the signal-to-noise ratio, and adhering such an electrode to the brain surface becomes critical. The most straightforward approach requires increasing the array conformability with flexible substrates while improving the electrode performance using materials with superior electrochemical properties. In this paper, we propose an ultra-flexible and conformable polyimide-based micro-ECoG array of submillimeter recording sites electrochemically coated with high surface area conductive polymer-carbon nanotube composites to improve their brain-electrical coupling capabilities. We characterized our devices both electrochemically and by recording from rat somatosensory cortex in vivo. The performance of the coated and uncoated electrodes was directly compared by simultaneously recording the same neuronal activity during multiwhisker deflection stimulation. Finally, we assessed the effect of electrode size on the extraction of somatosensory evoked potentials and found that in contrast to the normal high-impedance microelectrodes, the recording capabilities of our low-impedance microelectrodes improved upon reducing their size from 0.2 to 0.1 mm.

A multi-channel low-power system-on-chip for single-unit recording and narrowband wireless transmission of neural signal

This paper reports a multi-channel neural recording system-on-chip (SoC) with digital data compression and wireless telemetry. The circuit consists of a 16 amplifiers, an analog time division multiplexer, an 8-bit SAR AD converter, a digital signal processor (DSP) and a wireless narrowband 400-MHz binary FSK transmitter. Even though only 16 amplifiers are present in our current die version, the whole system is designed to work with 64 channels demonstrating the feasibility of a digital processing and narrowband wireless transmission of 64 neural recording channels. A digital data compression, based on the detection of action potentials and storage of correspondent waveforms, allows the use of a 1.25-Mbit/s binary FSK wireless transmission. This moderate bit-rate and a low frequency deviation, Manchester-coded modulation are crucial for exploiting a narrowband wireless link and an efficient embeddable antenna. The chip is realized in a 0.35- εm CMOS process with a power consumption of 105 εW per channel (269 εW per channel with an extended transmission range of 4 m) and an area of 3.1 × 2.7 mm2. The transmitted signal is captured by a digital TV tuner and demodulated by a wideband phase-locked loop (PLL), and then sent to a PC via an FPGA module. The system has been tested for electrical specifications and its functionality verified in in-vivo neural recording experiments.

Microelectronics, bioinformatics and neurocomputation for massive neuronal recordings in brain circuits with large scale multielectrode array probes.

Deciphering neural network function in health and disease requires recording from many active neurons simultaneously. Developing approaches to increase their numbers is a major neurotechnological challenge. Parallel to recent advances in optical Ca(2+) imaging, an emerging approach consists in adopting complementary-metal-oxide-semiconductor (CMOS) technology to realize MultiElectrode Array (MEA) devices. By implementing signal conditioning and multiplexing circuits, these devices allow nowadays to record from several thousands of single neurons at sub-millisecond temporal resolution. At the same time, these recordings generate very large data streams which become challenging to analyze. Here, at first we shortly review the major approaches developed for data management and analysis for conventional, low-resolution MEAs. We highlight how conventional computational tools cannot be easily up-scaled to very large electrode array recordings, and custom bioinformatics tools are an emerging need in this field. We then introduce a novel approach adapted for the acquisition, compression and analysis of extracellular signals acquired simultaneously from 4096 electrodes with CMOS MEAs. Finally, as a case study, we describe how this novel large scale recording platform was used to record and analyze extracellular spikes from the ganglion cell layer in the wholemount retina at pan-retinal scale following patterned light stimulation.

A programmable closed-loop recording and stimulating wireless system for behaving small laboratory animals

A portable 16-channels microcontroller-based wireless system for a bi-directional interaction with the central nervous system is presented in this work. The device is designed to be used with freely behaving small laboratory animals and allows recording of spontaneous and evoked neural activity wirelessly transmitted and stored on a personal computer. Biphasic current stimuli with programmable duration, frequency and amplitude may be triggered in real-time on the basis of the recorded neural activity as well as by the animal behavior within a specifically designed experimental setup. An intuitive graphical user interface was developed to configure and to monitor the whole system. The system was successfully tested through bench tests and in vivo measurements on behaving rats chronically implanted with multi-channels microwire arrays.

Modeling, Evaluation, and Comparison of CRZ and RSD Redundant Architectures for Two-Step A/D Converters

Redundancy in the output code as an instrument to reduce the impact of nonidealities in different architectures of two-step analog to digital converters (ADC) is investigated. The CRZ converters, which are the converters obtained from the conventional CR architecture with addition of Z extra decision levels, are formalized and compared with the RSD converter. Two distinct models are proposed to investigate separately, by means of system level simulations, the impact of each source of error: the behavioral model and the circuit model. The first one is intended to give an intuitive understanding of how redundancy improves the output response of this class of converters, while the latter is introduced to find, at an early design stage, the optimum sizing of passive components meeting a given resolution. Simulation results from both models are discussed and the different performances of the various converters are evaluated with respect to power, area, and effective resolution.

Ultra-flexible and brain-conformable micro-electrocorticography device with low impedance PEDOT-carbon nanotube coated microelectrodes

Electrocorticography, thanks to its low degree of invasiveness, has received in recent years an increasing attention for chronic brain-machine interface applications. To be up to the task, electrocorticography electrode arrays can benefit from several improvements. Better recording abilities can be obtained through smaller, low impedance and high density electrodes, while conformability can provide superior adhesion to the cortex surface and lower biological impact. In this work we present an ultra-flexible and brain-conformable polyimide-based micro-ECoG array with low-impedance poly(3,4-ethylenedioxythiophene) (PEDOT)-carbon nanotube coated microelectrodes. A first in vivo validation of our device is performed on rat somatosensory cortex.

Independent Component Decomposition of Human Somatosensory Evoked Potentials Recorded by Micro-Electrocorticography.

High-density surface microelectrodes for electrocorticography (ECoG) have become more common in recent years for recording electrical signals from the cortex. With an acceptable invasiveness/signal fidelity trade-off and high spatial resolution, micro-ECoG is a promising tool to resolve fine task-related spatial-temporal dynamics. However, volume conduction - not a negligible phenomenon - is likely to frustrate efforts to obtain reliable and resolved signals from a sub-millimeter electrode array. To address this issue, we performed an independent component analysis (ICA) on micro-ECoG recordings of somatosensory-evoked potentials (SEPs) elicited by median nerve stimulation in three human patients undergoing brain surgery for tumor resection. Using well-described cortical responses in SEPs, we were able to validate our results showing that the array could segregate different functional units possessing unique, highly localized spatial distributions. The representation of signals through the root-mean-square (rms) maps and the signal-to-noise ratio (SNR) analysis emphasizes the advantages of adopting a source analysis approach on micro-ECoG recordings in order to obtain a clear picture of cortical activity. The implications are twofold: while on one side ICA may be used as a spatial-temporal filter extracting micro-signal components relevant to tasks for brain-computer interface (BCI) applications, it could also be adopted to accurately identify the sites of nonfunctional regions for clinical purposes.