Multichannel Microelectrode Arrays Research Articles

High-Throughput Microelectrode Arrays for Precise Functional Localization of the Globus Pallidus Internus.

The globus pallidus internus (GPi) was considered a common target for stimulation in Parkinson's disease (PD). Located deep in the brain and of small size, pinpointing it during surgery is challenging. Multi-channel microelectrode arrays (MEAs) can provide micrometer-level precision functional localization, which can maximize the surgical outcome. In this paper, a 64-channel MEA modified by platinum nanoparticles with a detection site impedance of 61.1 kΩ was designed and prepared, and multiple channels could be synchronized to cover the target brain region and its neighboring regions so that the GPi could be identified quickly and accurately. The results of the implant trajectory indicate that, compared to the control side, there is a reduction in local field potential (LFP) power in multiple subregions of the upper central thalamus on the PD-induced side, while the remaining brain regions exhibit an increasing trend. When the MEA tip was positioned at 8,700 μm deep in the brain, the various characterizations of the spike signals, combined with the electrophysiological characteristics of the β-segmental oscillations in PD, enabled MEAs to localize the GPi at the single-cell level. More precise localization could be achieved by utilizing the distinct characteristics of the internal capsule (ic), the thalamic reticular nucleus (Rt), and the peduncular part of the lateral hypothalamus (PLH) brain regions, as well as the relative positions of these brain structures. The MEAs designed in this study provide a new detection method and tool for functional localization of PD targets and PD pathogenesis at the cellular level.

Multi-channel microelectrode arrays for detection of single-cell level neural information in the hippocampus CA1 under general anesthesia induced by low-dose isoflurane

Timely monitoring of anesthesia status during surgery is important to prevent an overdose of isoflurane anesthesia. Therefore, in-depth studies of the neural mechanisms of anesthetics are warranted. Hippocampal CA1 plays an important role during anesthesia. Currently, a high spatiotemporal resolution microdevice technology for the accurate detection of deep brain nuclei is lacking. In this research, four-shank 32-channel implantable microelectrode arrays (MEAs) were developed for the real-time recording of single-cell level neural information in rat hippocampal CA1. Platinum nanoparticles were modified onto the microelectrodes to substantially enhance the electrical properties of the microelectrode arrays. The modified MEAs exhibited low impedance (11.5 ± 1 kΩ) and small phase delay (-18.5 ± 2.54°), which enabled the MEAs to record single-cell level neural information with a high signal-to-noise ratio. The MEAs were implanted into the CA1 nuclei of the anesthetized rats, and the electrophysiological signals were recorded under different degrees of anesthesia mediated by low-dose concentrations of isoflurane. The recorded signals were analyzed in depth. Isoflurane caused an inhibition of spike firing rate in hippocampal CA1 neurons, while inducing low-frequency oscillations in CA1, thus enhancing the low-frequency power of local field potentials. In this manner, the spike firing rate and the power of local field potentials in CA1 could characterize the degree of isoflurane anesthesia. The present study provides a technical tool to study the neural mechanisms of isoflurane anesthesia and a research method for monitoring the depth of isoflurane anesthesia in clinical practice.

Wafer-Scale Fabrication and Assembly Method of Multichannel Microelectrode Arrays for ECoG Application

High density electrocorticography (ECoG)-based microelectrode arrays (MEAs) are fabricated to timely record the neural activities to provide the fundamental understanding in neuroscience and biomedical engineering. This paper aims to introduce a device-based concept and wafer-scale fabrication process for MEAs. Flexible and biocompatible polyimide is applied on MEAs to bear all possible stress and strain. Detailed fabrication key techniques, including surface treatment, polyimide stability measurement, evaporation process, and curing conditions, have been discussed thoroughly. Moreover, the fabricated polyimide-based MEAs are surface-mounted on well-packaged printed circuit boards (PCBs) via a slot-type connector without any additional wire bonding to make the signal recording process easier. An absence seizure was recorded during the in vivo test, which shows the availability of signal recording based on the presented MEAs. The proposed MEAs could be remained at the skull, while the connector and PCBs can be disassembled apart. Therefore, the testing sample will get less suffering. To verify the robustness of the fabricated MEAs, the impedance properties were characterized using electrochemical impedance spectroscopy. The measured results indicate an average impedance of 12.3 ± 0.675 kΩ at 1 kHz. In total, 10 groups of MEAs were sample tested, and over 90% of the total 60 channels per 1-MEAs operated efficiently.

Construction of simple, customised, brain-spanning, multi-channel, linear microelectrode arrays

BackgroundThe construction of multichannel micro-electrode arrays (MEA) generally requires complex and expensive procedures. Here we describe a simple, cheap, flexible method of linear MEA construction. New methodOur method allows manufacture of linear MEA (cross section ∼ 375 × 250 μm with 12 electrodes) of any desired length, with customized spacing of the electrode tips (down to a minimum spacing of 200 μm or less) to suit different needs and experiments. We describe the following steps: (1) set-up for MEA construction; (2) building of a construction jig; (3) building the reference, ground and optional electrical stimulation electrodes; (4) treatment of the main recording microwires; (5) soldering of the microwires to the main connector plug and arrangement of the microwires in a customizable array; and (6) testing of the MEA resistance and correct connections. Finally, we describe methods for quick surgical implantation of multiple MEAs and bipolar micro-stimulation electrodes for in vivo experiments in free-moving rats. ResultsWe provide examples of multi-site local field potentials from prolonged recordings in awake and free-moving rodents, with recordings viable for months, as well as samples of electrical stimulation effects on cortical and hippocampal recordings. Hippocampal recordings showed clear phase reversal and amplitude changes across its layers. ConclusionsWe briefly discuss how the arrays can support other forms of stimulation such as optogenetic probes.

DRG microstimulation evokes postural responses in awake, standing felines

Objective. We have demonstrated previously that microstimulation in the dorsal root ganglia (DRG) can selectively evoke activity in primary afferent neurons in anesthetized cats. This study describes the results of experiments focused on characterizing the postural effects of DRG microstimulation in awake cats during quiet standing. Approach. To understand the parameters of stimulation that can affect these postural shifts, we measured changes in ground reaction forces (GRF) while varying stimulation location and amplitude. Four animals were chronically implanted at the L6 and L7 DRG with penetrating multichannel microelectrode arrays. During each week of testing, we identified electrode channels that recruited primary afferent neurons with fast (80–120 m s−1) and medium (30–75 m s−1) conduction velocities, and selected one channel to deliver current-controlled biphasic stimulation trains during quiet standing. Main results. Postural responses were identified by changes in GRFs and were characterized based on their magnitude and latency. During DRG microstimulation, animals did not exhibit obvious signs of distress or discomfort, which could be indicative of pain or aversion to a noxious sensation. Across 56 total weeks, 13 electrode channels evoked behavioral responses, as detected by a significant change in GRF. Stimulation amplitude modulated the magnitude of the GRF responses for these 13 channels (p < 0.001). It was not possible to predict whether or not an electrode would drive a behavioral response based on information including conduction velocity, recruitment threshold, or the DRG in which it resided. Significance. The distinct and repeatable effects on the postural response to low amplitude (<40 µA) DRG microstimulation support that this technique may be an effective way to restore somatosensory feedback after neurological injuries such as amputation.

Well Controlled 3D Iridium Oxide/Platinum Nanocomposites with Greatly Enhanced Electrochemical Performances

AbstractIt is crucial to improve charge storage capacity (CSC) and charge transport efficiency with low impedance for electrochemical capacitors. Here, a well‐controlled three‐dimensional (3D) nanocrystal platinum (Pt) is electrodeposited as the intermediate layer on microelectrode (200 µm in diameter) to provide extensive large surface area, followed by introducing iridium oxide (IrOx) nanoparticles with excellent adhesion on the rough layer to fabricate high‐performance IrOx/Pt composite coatings. The uniform flower‐shaped coating presents a significantly low impedance ≈2.01 kΩ at 1 kHz (reduction of 94.52%). It has a cathodic CSC (CSCc) up to ≈200.64 mC cm−2, about 2, 17.51, and 56.18 times higher than that of nanocrystal Pt, IrOx, and flat Pt respectively. Robust chronic stability is observed with CSCc at ≈171.97 mC cm−2 after electrical stimulation for 12 d (&gt;1 × 108 cycles). It also demonstrates record‐high charge injection capacity ≈6.37 mC cm−2 with excellent biocompatibility. Such coating is widely applicable for batch production on multichannel microelectrode arrays or substrates with different sizes. Moreover, it promotes excellent sensitivity to glucose detection up to ≈130 µA cm−2 mm−1, with a linear range of 1–30 × 10−3 m and a detection limit of 1.08 × 10−6 m. The promising coating will pave a new way for various electrochemical applications.

Fabrication and evaluation of nanostructured microelectrodes for high-spatial resolution in retinal prostheses

To provide visual information to patients with retinal degenerative disease, retinal prosthetic devices based on multi-channel microelectrode arrays (MEAs) have shown some promising results. For high-quality information, the number of microelectrodes should be increased in the limited area of MEAs, which results in decreased dimensions of the single microelectrode and a limit of dynamic range of injection current. Previously, our research group has presented 3D microelectrodes to overcome the trade-off between high-spatial resolution and injection current range. However, the 3D microelectrode requires a complex fabrication process, including multiple steps in front-side and back-side microfabrication. In this paper, the nanostructured microelectrode with platinum-black is fabricated with a simple process, and its electrical characteristics are evaluated. The nanostructured microelectrode parameters are analyzed by a conventional three-element circuit model. The comprehensive electrical characteristics between planar 2D, 3D, and nanostructured microelectrodes with various base areas are compared by measuring electrode–electrolyte interface impedance and maximum allowable injection current limit. The experimental results show improved interface impedance in nanostructured microelectrodes compared to planar 2D and 3D microelectrodes with same base area. This implies that nanostructured microelectrodes have a large dynamic range for current stimulation, which can be more sufficient in retinal neuron stimulation. This research can be used to estimate the theoretical limit of injection current for high-resolution MEAs.

Stimulation triggers endogenous activity patterns in cultured cortical networks

Cultures of dissociated cortical neurons represent a powerful trade-off between more realistic experimental models and abstract modeling approaches, allowing to investigate mechanisms of synchronized activity generation. These networks spontaneously alternate periods of high activity (i.e. network bursts) with periods of quiescence in a dynamic state which recalls the fluctuation of in vivo UP and DOWN states. Network bursts can also be elicited by external stimulation and their spatial propagation patterns tracked by means of multi-channel micro-electrode arrays. In this study, we used rat cortical cultures coupled to micro-electrode arrays to investigate the similarity between spontaneous and evoked activity patterns. We performed experiments by applying electrical stimulation to different network locations and demonstrated that the rank orders of electrodes during evoked and spontaneous events are remarkably similar independently from the stimulation source. We linked this result to the capability of stimulation to evoke firing in highly active and “leader” sites of the network, reliably and rapidly recruited within both spontaneous and evoked bursts. Our study provides the first evidence that spontaneous and evoked activity similarity is reliably observed also in dissociated cortical networks.

Wireless Cortical Brain-Machine Interface for Whole-Body Navigation in Primates

Several groups have developed brain-machine-interfaces (BMIs) that allow primates to use cortical activity to control artificial limbs. Yet, it remains unknown whether cortical ensembles could represent the kinematics of whole-body navigation and be used to operate a BMI that moves a wheelchair continuously in space. Here we show that rhesus monkeys can learn to navigate a robotic wheelchair, using their cortical activity as the main control signal. Two monkeys were chronically implanted with multichannel microelectrode arrays that allowed wireless recordings from ensembles of premotor and sensorimotor cortical neurons. Initially, while monkeys remained seated in the robotic wheelchair, passive navigation was employed to train a linear decoder to extract 2D wheelchair kinematics from cortical activity. Next, monkeys employed the wireless BMI to translate their cortical activity into the robotic wheelchair’s translational and rotational velocities. Over time, monkeys improved their ability to navigate the wheelchair toward the location of a grape reward. The navigation was enacted by populations of cortical neurons tuned to whole-body displacement. During practice with the apparatus, we also noticed the presence of a cortical representation of the distance to reward location. These results demonstrate that intracranial BMIs could restore whole-body mobility to severely paralyzed patients in the future.

Intralaminar stimulation of the inferior colliculus facilitates frequency-specific activation in the auditory cortex

Objective. Auditory midbrain implants (AMI) provide inadequate frequency discrimination for open set speech perception. AMIs that can take advantage of the tonotopic laminar of the midbrain may be able to better deliver frequency specific perception and lead to enhanced performance. Stimulation strategies that best elicit frequency specific activity need to be identified. This research examined the characteristic frequency (CF) relationship between regions of the auditory cortex (AC), in response to stimulated regions of the inferior colliculus (IC), comparing monopolar, and intralaminar bipolar electrical stimulation. Approach. Electrical stimulation using multi-channel micro-electrode arrays in the IC was used to elicit AC responses in anaesthetized male hooded Wistar rats. The rate of activity in AC regions with CFs within 3 kHz (CF-aligned) and unaligned CFs was used to assess the frequency specificity of responses. Main results. Both monopolar and bipolar IC stimulation led to CF-aligned neural activity in the AC. Altering the distance between the stimulation and reference electrodes in the IC led to changes in both threshold and dynamic range, with bipolar stimulation with 400 µm spacing evoking the lowest AC threshold and widest dynamic range. At saturation, bipolar stimulation elicited a significantly higher mean spike count in the AC at CF-aligned areas than at CF-unaligned areas when electrode spacing was 400 µm or less. Bipolar stimulation using electrode spacing of 400 µm or less also elicited a higher rate of elicited activity in the AC in both CF-aligned and CF-unaligned regions than monopolar stimulation. When electrodes were spaced 600 µm apart no benefit over monopolar stimulation was observed. Furthermore, monopolar stimulation of the external cortex of the IC resulted in more localized frequency responses than bipolar stimulation when stimulation and reference sites were 200 µm apart. Significance. These findings have implications for the future development of AMI, as a bipolar stimulation strategy may improve the ability of implant users to discriminate between frequencies.

An Area-Efficient Noise-Adaptive Neural Amplifier in 130 nm CMOS Technology

Chronic recording of neural signals is indispensable in designing efficient brain-machine interfaces and to elucidate human neurophysiology. The advent of multichannel micro-electrode arrays has driven the need for electronics to record neural signals from many neurons. The dynamic range of the system can vary over time due to change in electrode-neuron distance and background noise. We propose a neural amplifier in UMC 130 nm, 1P8M complementary metal-oxide-semiconductor (CMOS) technology. It can be biased adaptively from 200 nA to 2 μA, modulating input referred noise from 9.92 μV to 3.9 μV. We also describe a low noise design technique which minimizes the noise contribution of the load circuitry. Optimum sizing of the input transistors minimizes the accentuation of the input referred noise of the amplifier and obviates the need of large input capacitance. The amplifier achieves a noise efficiency factor of 2.58. The amplifier can pass signal from 5 Hz to 7 kHz and the bandwidth of the amplifier can be tuned for rejecting low field potentials (LFP) and power line interference. The amplifier achieves a mid-band voltage gain of 37 dB. In vitro experiments are performed to validate the applicability of the neural low noise amplifier in neural recording systems.

Efficacy and reliability of long-term implantation of multi-channel microelectrode arrays in the optical nerve sheath of rabbit eyes

In addition to epiretinal and subretinal areas, the optic nerve (ON) is also a candidate location for implanting visual prosthesis to restore vision of patients with retinitis pigmentosa (RP). Since the ON receives all the signals from the retina, stimulating the ON may potentially evoke phosphenes over a wider range of visual field. In this study, we designed a 9-channel microelectrode array and implanted it between the dura mater and pia mater of rabbit ONs by lateral orbitotomy. We recorded the current thresholds and evaluated the efficacy of the array using electrically evoked potentials (EEPs). Spatial discrimination of approximately 20° was verified by EEP maps over visual cortex. A large area of the visual field (over 130° along horizontal meridian) could be activated by this microelectrode array. Visual evoked potentials (VEPs) and different pathological examinations were used to examine potential damage of ONs. One year post implantation, we did not notice significant damages to either the ONs or the microelectrode arrays. EEPs were successfully recorded up to 6months post implantations. However, further studies are still needed to reduce fibrous encapsulation of the microelectrode array, which resulted in a gradual elevation of current thresholds to elicit EEPs.

Liquid state machines and cultured cortical networks: The separation property

In vitro neural networks of cortical neurons interfaced to a computer via multichannel microelectrode arrays (MEA) provide a unique paradigm to create a hybrid neural computer. Unfortunately, only rudimentary information about these in vitro network’s computational properties or the extent of their abilities are known. To study those properties, a liquid state machine (LSM) approach was employed in which the liquid (typically an artificial neural network) was replaced with a living cortical network and the input and readout functions were replaced by the MEA–computer interface. A key requirement of the LSM architecture is that inputs into the liquid state must result in separable outputs based on the liquid’s response (separation property). In this paper, high and low frequency multi-site stimulation patterns were applied to the living cortical networks. Two template-based classifiers, one based on Euclidean distance and a second based on a cross-correlation were then applied to measure the separation of the input–output relationship. The result was over a 95% (99.8% when nonstationarity is compensated) input reconstruction accuracy for the high and low frequency patterns, confirming the existence of the separation property in these biological networks.

A low-noise demultiplexing system for active multichannel microelectrode arrays

This paper reports a low-noise demultiplexing system capable of reconstructing multichannel single-unit neural signals derived from multiplexed microelectrode arrays. The overall multiplexing-demultiplexing system realizes ten channels, a per-channel gain of 68 dB, a bandwidth from 100 Hz to 6 kHz, and an equivalent noise level (referred to the probe input) of 13 microV rms. It provides for signaling over the power supply to allow control of on-chip probe functions such as self-testing. The interchannel crosstalk is less than 3%, and switching noise is suppressed by blanking the transition intervals. The 200 kHz probe sample clock is tracked automatically over a range from 150 to 250 kHz. Neural signals as low as 20 microV (typically 640 microV at the demultiplexing system input) can be reconstructed. The overall system organization is compatible with the demultiplexing of as many as 40 time-multiplexed electrode channels from a single probe data line.

Visual areas I and II of cerebral cortex of rabbit.

Visual areas I and II of cerebral cortex of rabbit.