Neural Signal Recording Research Articles

Flexible polyimide-based hybrid opto-electric neural interface with 16 channels of micro-LEDs and electrodes

In this paper, a polyimide-based flexible device that integrates 16 micro-LEDs and 16 IrOx-modified microelectrodes for synchronous photostimulation and neural signal recording is presented. The 4 × 4 micro-LEDs (dimensions of 220 × 270 × 50 μm3, 700 μm pitch) are fixed in the SU-8 fence structure on a polyimide substrate and connected to the leads via a wire-bonding method. The recording electrodes share a similar fabrication process on the polyimide with 16 microelectrode sites (200 μm in diameter and 700 μm in pitch) modified by iridium oxide (IrOx). These two subparts can be aligned with alignment holes and glued back-to-back by epoxy, which ensures that the light from the LEDs passes through the corresponding holes that are evenly distributed around the recording sites. The long-term electrical and optical stabilities of the device are verified using a soaking test for 3 months, and the thermal property is specifically studied with different duty cycles, voltages, and frequencies. Additionally, the electrochemical results prove the reliability of the IrOx-modified microelectrodes after repeated pressing or friction. To evaluate the tradeoff between flexibility and strength, two microelectrode arrays with thicknesses of 5 and 10 μm are evaluated through simulation and experiment. The proposed device can be a useful mapping optogenetics tool for neuroscience studies in small (rats and mice) and large animal subjects and ultimately in nonhuman primates.

A Meta-Analysis of Intracortical Device Stiffness and Its Correlation with Histological Outcomes.

Neural implants offer solutions for a variety of clinical issues. While commercially available devices can record neural signals for short time periods, they fail to do so chronically, partially due to the sustained tissue response around the device. Our objective was to assess the correlation between device stiffness, a function of both material modulus and cross-sectional area, and the severity of immune response. Meta-analysis data were derived from nine previously published studies which reported device material and geometric properties, as well as histological outcomes. Device bending stiffness was calculated by treating the device shank as a cantilevered beam. Immune response was quantified through analysis of immunohistological images from each study, specifically looking at fluorescent markers for neuronal nuclei and astrocytes, to assess neuronal dieback and gliosis. Results demonstrate that the severity of the immune response, within the first 50 µm of the device, is highly correlated with device stiffness, as opposed to device modulus or cross-sectional area independently. In general, commercially available devices are around two to three orders of magnitude higher in stiffness than devices which induced a minimal tissue response. These results have implications for future device designs aiming to decrease chronic tissue response and achieve increased long-term functionality.

Positioning the Nerve Cuff Distally on the Sciatic Nerve Improves the Classification of Ankle-Movement Proprioceptive ENG Signals.

Recording of neural signals from intact peripheral nerves in patients with spinal cord injury or stroke survivors offers the possibility for the development of closed-loop sensorimotor prostheses. However, questions remain over the positioning of neural interfaces such that the separability of neural data recorded from the peripheral nerves is improved. Afferent electroneurographic signals were recorded with nerve cuffs placed on the sciatic nerve of rats in response to various mechanical stimuli to the hindpaw. The mean absolute value of the signal was extracted and fed into classifiers. The performance of the classifier was evaluated when information was available from a single cuff placed either distally or proximally on the sciatic nerve. Results confirmed earlier findings that proprioceptive ENG signals, elicited by the movement of the ankle, can be identified and separated in neural recordings made with a cuff electrode. In addition, classification scores improved when the nerve cuff was placed distally on the nerve rather than proximally, taking advantage of the nerve's underlying anatomy.

A biodegradable porous silicon and polymeric hybrid probe for electrical neural signal recording

This paper reports on a novel design and fabrication strategy to develop a hybrid porous silicon (PSi)-polyimide-based neural interface probe. The PSi is soluble in the tissue matrix, leaving the flexible polyimide shank inside the tissue as a permanent probe-implant. The flexibility of the PSi-dissolved polyimide shank is possible to reduce the tissue response, resulting from the probe-implant. In-vitro degradation experiment was conducted in phosphate buffer solution (PBS), pH 7.4, at 37 °C. The PSi with over 50% porosity was dissolved in less than 6 days. The electrode contacts were made of Au or Pt; impedance measurements gave values of 6.83 MΩ and 656 kΩ @1 kHz, respectively. The minimum critical bucking force among the fabricated probes was tested to be 71 mN, corresponding to the highest porosities of 70% and 5 mm shank length. Assessment of the cell viability was done using mouse fibroblast cell line, indicating that there was no sign of obvious cell lysis and reduction of cell growth on the device surface. Lastly, the functionality of the probe was proved by successful implantation in rat cortex. The local field potential action spikes were recorded with ±40 μV peak and signal to noise ratio of 7.8.

Influence of nerve cuff channel count and implantation site on the separability of afferent ENG

Objective. Recording of neural signals from intact peripheral nerves in patients with spinal cord injury or stroke survivors offers the possibility for the development of closed-loop sensorimotor prostheses. Nerve cuffs have been found to provide stable recordings from peripheral nerves for prolonged periods of time. However, questions remain over the design and positioning of nerve cuffs such that the separability of neural data recorded from the peripheral nerves is improved. Approach. Afferent electroneurographic (ENG) signals were recorded with nerve cuffs placed on the sciatic nerve of rats in response to various mechanical stimuli to the hindpaw. The mean absolute value of the signal was extracted and input to a classifier. The performance of the classifier was evaluated under two conditions: (1) when information from either a 3- or 16-channel cuff was used; (2) when information was available from a cuff placed either distally or proximally along the nerve. Main results. We show that both 3- and 16-channel cuffs were able to separate afferent ENG signals with an accuracy greater than chance. The highest classification scores were achieved when the classifier was fed with information obtained from a 16-channel cuff placed distally. While the 16-channel cuff always outperformed the 3-channel cuff, the difference in performance was increased when the 16-channel cuff was placed distally rather than proximally on the nerve. Significance. The results indicate that increasing the complexity of a nerve cuff may only be advantageous if the nerve cuff is to be implanted distally, where the nerve has begun to divide into individual fascicles.

Recovery of early neural spikes from stimulation electrodes using a DC-coupled low gain high resolution data acquisition system

BackgroundNeural responses to electrical stimulation provide valuable information to probe and study the network function. Especially, recording neural responses from the stimulated site provides improved neural interfacing method. However, it is difficult to measure short-delayed responses at the stimulated electrode due to the saturation of the amplifier after stimulation which is called “stimulus artifact”. Despite the advances in handling stimulation artifacts, it is still very challenging to deal with the artifacts if one tries to stimulate and record from the same electrode. New methodIn this paper, we developed a system consisting of 24 bit ADC and low gain DC-amplifier which allows us to record the entire responses including saturation-free stimulus artifact and neural responses with excellent resolution. ResultsOur approach showed saturation-free recording after stimulation, which makes it possible to recover neural spike as early as in 2 ms at the stimulating electrode with digital elimination methods. Comparison with Existing methodsWith our system we could record neural signals after stimulation that was difficult with high gain and high pass filtered recording system due to amplifier saturation. ConclusionsOur new system can enhance interface performance with its higher robustness and with simple system configuration.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Development of an ex Vivo Method for Multi-unit Recording of Microbiota-Colonic-Neural Signaling in Real Time.

Background and Objectives: Bidirectional signaling between the gastrointestinal tract and the brain is vital for maintaining whole-body homeostasis. Moreover, emerging evidence implicates vagal afferent signaling in the modulation of host physiology by microbes, which are most abundant in the colon. This study aims to optimize and advance dissection and recording techniques to facilitate real-time recordings of afferent neural signals originating in the distal colon.New Protocol: This paper describes a dissection technique, which facilitates extracellular electrophysiological recordings from visceral pelvic, spinal and vagal afferent neurons in response to stimulation of the distal colon.Examples of Application: Focal application of 75 mM KCl to a section of distal colon with exposed submucosal or myenteric nerve cell bodies and sensory nerve endings evoked activity in the superior mesenteric plexus and the vagal nerve. Noradrenaline stimulated nerve activity in the superior mesenteric plexus, whereas application of carbachol stimulated vagal nerve activity. Exposure of an ex vivo section of distal colon with an intact colonic mucosa to peptidoglycan, but not lipopolysaccharide, evoked vagal nerve firing.Discussion: Previous studies have recorded vagal signaling evoked by bacteria in the small intestine. The technical advances of this dissection and recording technique facilitates recording of afferent nerve signals evoked in extrinsic sensory pathways by neuromodulatory reagents applied to the distal colon. Moreover, we have demonstrated vagal afferent activation evoked by bacterial products applied to the distal colonic mucosa. This protocol may contribute to our understanding of functional bowel disorders where gut-brain communication is dysfunctional, and facilitate real-time interrogation of microbiota-gut-brain signaling.

Evaluating the in vivo glial response to miniaturized parylene cortical probes coated with an ultra-fast degrading polymer to aid insertion

Objective. Despite the feasibility of short-term neural recordings using implantable microelectrodes, attaining reliable, chronic recordings remains a challenge. Most neural recording devices suffer from a long-term tissue response, including gliosis, at the device–tissue interface. It was hypothesized that smaller, more flexible intracortical probes would limit gliosis by providing a better mechanical match with surrounding tissue. Approach. This paper describes the in vivo evaluation of flexible parylene microprobes designed to improve the interface with the adjacent neural tissue to limit gliosis and thereby allow for improved recording longevity. The probes were coated with an ultrafast degrading tyrosine-derived polycarbonate (E5005(2K)) polymer that provides temporary mechanical support for device implantation, yet degrades within 2 h post-implantation. A parametric study of probes of varying dimensions and polymer coating thicknesses were implanted in rat brains. The glial tissue response and neuronal loss were assessed from 72 h to 24 weeks post-implantation via immunohistochemistry. Main results. Experimental results suggest that both probe and polymer coating sizes affect the extent of gliosis. When an appropriate sized coating dimension (100 µm × 100 µm) and small probe (30 µm × 5 µm) was implanted, a minimal post-implantation glial response was observed. No discernible gliosis was detected when compared to tissue where a sham control consisting of a solid degradable polymer shuttle of the same dimensions was inserted. A larger polymer coating (200 µm × 200 µm) device induced a more severe glial response at later time points, suggesting that the initial insertion trauma can affect gliosis even when the polymer shuttle degrades rapidly. A larger degree of gliosis was also observed when comparing a larger sized probe (80 µm × 5 µm) to a smaller probe (30 µm × 5 µm) using the same polymer coating size (100 µm × 100 µm). There was no significant neuronal loss around the implantation sites for most device candidates except the group with largest polymer coating and probe sizes. Significance. These results suggest that: (1) the degree of mechanical trauma at device implantation and mechanical mismatches at the probe-tissue interface affect long term gliosis; (2) smaller, more flexible probes may minimize the glial response to provide improved tissue biocompatibility when used for chronic neural signal recording; and (3) some degree of glial scarring did not significantly affect neuronal distribution around the probe.

Thermo-plasmonic gold nanofilms for simple and mass-producible photothermal neural interfaces.

In recent years, photothermal stimulation methods using plasmonic metal nanoparticles have emerged as non-genetic optical techniques in neuromodulation. Although nanoparticle-based photothermal stimulation shows great potential in the excitation and the inhibition of neural activity, the complex synthesis processes of the nanoparticles and the lack of large-area deposition methods can be limiting factors for the development of photothermal neural devices. In this paper, we propose a plasmonic gold nanofilm, fabricated by a standard thermal evaporation process, as a simple and mass-producible photothermal neural interface layer for microelectrode array (MEA) chips. The absorption of the gold nanofilm at near infrared wavelengths is optimized to maximize the photothermal effect by varying the thickness and microstructure of the gold nanofilm. With the optimized conditions, a significantly strong photothermal effect is applied on MEAs without affecting the neural signal recording capability. Finally, primary rat hippocampal neuronal cultures are used to show that the photothermal neural inhibition using the gold nanofilm is as effective as that using the plasmonic nanoparticles. Due to the greater simplicity and versatility of the fabrication process, the plasmonic gold nanofilm can provide a promising solution for the mass production of photothermal platforms.

A battery-less 15 Mbps data transmission in wireless neural signal recording system for BMI

A battery-less 15 Mbps data transmission in wireless neural signal recording system for BMI

An Implantable Wireless Neural Interface System for Simultaneous Recording and Stimulation of Peripheral Nerve with a Single Cuff Electrode.

Recently, implantable devices have become widely used in neural prostheses because they eliminate endemic drawbacks of conventional percutaneous neural interface systems. However, there are still several issues to be considered: low-efficiency wireless power transmission; wireless data communication over restricted operating distance with high power consumption; and limited functionality, working either as a neural signal recorder or as a stimulator. To overcome these issues, we suggest a novel implantable wireless neural interface system for simultaneous neural signal recording and stimulation using a single cuff electrode. By using widely available commercial off-the-shelf (COTS) components, an easily reconfigurable implantable wireless neural interface system was implemented into one compact module. The implantable device includes a wireless power consortium (WPC)-compliant power transmission circuit, a medical implant communication service (MICS)-band-based radio link and a cuff-electrode path controller for simultaneous neural signal recording and stimulation. During in vivo experiments with rabbit models, the implantable device successfully recorded and stimulated the tibial and peroneal nerves while communicating with the external device. The proposed system can be modified for various implantable medical devices, especially such as closed-loop control based implantable neural prostheses requiring neural signal recording and stimulation at the same time.

Carbon nano-structured neural probes show promise for magnetic resonance imaging applications

Objective. Previous animal studies have demonstrated that carbon nanotube (CNT) electrodes provide several advantages of preferential cell growth and better signal-to-noise ratio (SNR) when interfacing with brain neural tissue. This work explores another advantage of CNT electrodes, namely their MRI compatibility. MRI-compatible neural electrodes that do not produce image artifacts will allow simultaneous co-located functional MRI and neural signal recordings, which will help improve our understanding of the brain. Approach. Prototype CNT electrodes on polyimide substrates are fabricated and tested in vitro and in vivo in rat brain at 9.4 T. To understand the results of the in vitro and in vivo studies, a simulation model based on numerical computation of the magnetic field around a two-dimensional object in a tissue substrate is developed. Main Results. The prototype electrodes are found to introduce negligible image artifacts in structural and functional imaging sequences in vitro and in vivo. Simulation results confirm that CNT prototype electrodes produce less magnetic field distortion than traditional metallic electrodes due to a combination of both superior material properties and geometry. By using CNT films, image artifacts can be nearly eliminated at magnetic fields of strength up to 9.4 T. At the same time, the high surface area of a CNT film provides high charge transfer and enables neural local field potential recordings with an equal or better SNR than traditional electrodes. Significance. CNT film electrodes can be used for simultaneous MRI and electrophysiology in animal models to investigate fundamental neuroscience questions and clinically relevant topics such as epilepsy.

Hearables: feasibility of recording cardiac rhythms from head and in-ear locations.

Mobile technologies for the recording of vital signs and neural signals are envisaged to underpin the operation of future health services. For practical purposes, unobtrusive devices are favoured, such as those embedded in a helmet or incorporated onto an earplug. However, these locations have so far been underexplored, as the comparably narrow neck impedes the propagation of vital signals from the torso to the head surface. To establish the principles behind electrocardiogram (ECG) recordings from head and ear locations, we first introduce a realistic three-dimensional biophysics model for the propagation of cardiac electric potentials to the head surface, which demonstrates the feasibility of head-ECG recordings. Next, the proposed biophysics propagation model is verified over comprehensive real-world experiments based on head- and in-ear-ECG measurements. It is shown both that the proposed model is an excellent match for the recordings, and that the quality of head- and ear-ECG is sufficient for a reliable identification of the timing and shape of the characteristic P-, Q-, R-, S- and T-waves within the cardiac cycle. This opens up a range of new possibilities in the identification and management of heart conditions, such as myocardial infarction and atrial fibrillation, based on 24/7 continuous in-ear measurements. The study therefore paves the way for the incorporation of the cardiac modality into future ‘hearables’, unobtrusive devices for health monitoring.

A new algorithm for automatically detecting epileptiform spikes and its application in epilepsy models

Epilepsy is characterized by abnormally synchronized firing of neuronal populations, which is presented as epileptiform spikes in neural electrical signal recordings. In order to investigate the epileptiform spikes quantitatively, we designed a new window-based algorithm to automatically detect population spikes (PS) in acute epilepsy models in rat hippocampus CA1 region, and to calculate characteristic parameters of PS. Results show that the algorithm could recognize PS waveforms directly in wideband recording signals in epilepsy models induced by 4-aminopyridine (4-AP), a potassium channel blocker, or by picrotoxin (PTX), an antagonist of γ-aminobutyric acid A-type receptor. The PS detection ratios of the two epilepsy models were 94.2%±1.6% ( n=11) and 95.9%±1.9% ( n=12), respectively. The false positive ratios were 3.5%±2.3% ( n=11) and 4.8%±2.3% ( n=12), which were significantly lower than those of the conventional threshold method. Comparisons of the PS patterns between the 4-AP model and the PTX model showed that the PS of the 4-AP model had wider waveforms and fired more dispersedly with intervals mainly in the range of 100-700 ms. The PS of the PTX model fired as Burst with a higher firing rate and with intervals mainly in the range of 2-20 ms, resulting in a larger sum of spike amplitudes per second than the 4-AP model. Thus, the synchronous firing of neuronal populations in the PTX model was more intense than that in the 4-AP model. In conclusion, the new algorithm of PS detection can correctly detect and analyze epileptiform population spikes. It provides a useful tool of data analysis for investigating the underlying mechanism of seizure generation and for evaluating new therapeutics of epilepsy.

Polymer-based interconnection cables to integrate with flexible penetrating microelectrode arrays.

There have been various types of interconnection methods for neural interfacing electrodes, such as silicon ribbon cables, wire bonding and polymer-based cables. In this study, interconnection cables were developed for integration with a Flexible Penetrating Microelectrode Array (FPMA) that was previously developed for neural signal recording or stimulation. Polyimide and parylene C were selected as base materials for the interconnection cables as both materials can preserve the flexibility of the FPMA better than other interconnection methods such as silicon ribbon cable or wire bonding. We conducted durability tests to determine if the interconnection cables were suitable for in-vivo implantation, by long-term soaking of the cables in phosphate buffered saline solution. We measured the changes in impedance over time, and equivalent circuit models were used to analyze the electrochemical phenomena on the surface of the cables. Lastly, we implanted the cable-integrated electrodes device onto rabbit's sciatic nerve and recorded neural signals to prove the feasibility of the developed FPMA integration system.

A Neural Probe With Up to 966 Electrodes and Up to 384 Configurable Channels in 0.13 $\mu$m SOI CMOS.

In vivo recording of neural action-potential and local-field-potential signals requires the use of high-resolution penetrating probes. Several international initiatives to better understand the brain are driving technology efforts towards maximizing the number of recording sites while minimizing the neural probe dimensions. We designed and fabricated (0.13- μm SOI Al CMOS) a 384-channel configurable neural probe for large-scale in vivo recording of neural signals. Up to 966 selectable active electrodes were integrated along an implantable shank (70 μm wide, 10mm long, 20 μm thick), achieving a crosstalk of [Formula: see text] dB. The probe base (5 × 9 mm 2 ) implements dual-band recording and a 171.6Mbps digital interface. Measurement results show a total input-referred noise of 6.4 μ V rms and a total power consumption of 49.1 μW/channel.

Optical detection of brain activity using plasmonic ellipsometry technique

In spite of the existence of many techniques in the field of neural signal recording and mapping, the realm for emergence of novel methods is still open. One of the novel methods that attracts the researchers’ attention is neuroplasmonics which benefits from the voltage-sensitive plasmonics. However, this field faces two main ambiguities: the physical mechanism of voltage-sensitive sensing of plasmonics and second, the strength of recorded responses. In this paper, after replying briefly the first question, we go forward by proposing ellipsometry measurements as a strong and very sensitive characterization method for voltage-sensitive plasmonics. Here, the suggested parameter of effective delta (i.e. delta contrast) creates the opportunity to distinguish clearly the results of applying different voltages to biological solutions (i.e. Phosphate Buffer Solution and artificial Cerebrospinal Fluid) and brain tissue (i.e. cerebellum tissue). The strong response of effective delta for cerebellum tissue indicates that the stimulation of brain tissue via external potential redistributes the charges at the interface of metal and modulates its dielectric constant at Thomson-Fermi layer which subsequently, leads to the variation in surface plasmon resonance signal.

Co-deposition of carbon dots and reduced graphene oxide nanosheets on carbon-fiber microelectrode surface for selective detection of dopamine

In this work, carbon dots (CD) decorated graphene oxide (GO) nanosheets were electrochemically reduced and deposited onto carbon fiber (CF) to fabricate microelectrodes for highly sensitive and selective dopamine (DA) detection, in the presence of ascorbic acid (AA) and uric acid (UA). The results have shown that surface modification considerably increases the electrocatalytic activity of the carbon fiber microelectrode. Due to possible aggregation of the rGO sheets during deposition, modifying the microelectrode surface with rGO sheets alone cannot achieve the selectivity required for simultaneous detection of DA, AA and UA. Through attaching CD onto GO sheets, the rGO+CD/CF microelectrode performance was significantly improved. The existence of CD on GO sheets can effectively avoid inter-layer stacking of the rGO sheets and provide increased surface area for neurotransmitter-electrode interaction enhancement. The CD can also increase the charge storage capacity of GO sheets. This is the first report on applying both CD and rGO for surface modification of carbon fiber microelectrode. The rGO+CD/CF microelectrode has achieved a linear DA detection concentration range of 0.1–100μM, with a detection limit of 0.02μM. The sensitivity of the microelectrode towards DA was as high as 6.5nA/μM, which is significantly higher than previously reported carbon fiber microelectrodes. The highly sensitive all-carbon based microelectrodes should find use in a number of biomedical applications, such as neurotransmitter detection, neural signal recording and cell physiology studies.

Low-impedance Tetrodes using Carbon Nanotube-Polypyrrole Composite Deposition

A tetrode is one of the neural electrodes, and it is widely used to record neural signals in the brain of a freely moving animal. The impedance of a neural electrode is an important parameter because it determines the signal-to-noise ratio of the recorded neural signals. Here, we developed a modification technique using carbon nanotube-polypyrrole composite nanostructures to decrease the impedances of tetrodes. The synthesis of the carbon nanotube and polypyrrole nanostructures was performed in two steps. In the first step, randomly dispersed carbon nanotubes and pyrrole monomers were gathered and aligned on the tetrode electrode. Next, they were electro-polymerized on the electrode surface. As the applied time (step-1 and step-2) and the offset voltage increased, the impedances of the tetrodes decreased. The modification technique is, therefore, an important and useful of lowering the impedances of tetrodes.