Corrigendum: Spatiotemporal analysis of 3D human iPSC-derived neural networks using a 3D multi-electrode array.

[This corrects the article DOI: 10.3389/fncel.2023.

Spatiotemporal analysis of 3D human iPSC-derived neural networks using a 3D multi-electrode array.

While there is a growing appreciation of three-dimensional (3D) neural tissues (i.e., hydrogel-based, organoids, and spheroids), shown to improve cellular health and network activity to mirror brain-like activity , functional assessment using current electrophysiology techniques (e.

Performance of three-dimensional printed nasopharyngeal swabs for COVID-19 testing.

Abstract: At the start of the COVID-19 pandemic, the US faced nationwide shortages of nasopharyngeal swabs due to both overwhelmed supply chains and an increase in demand. To address this shortfall, multiple 3D printed swabs were ultimately produced and sold for COVID-19 testing. In this work, we present a framework for mechanical and functional bench-testing of nasopharyngeal swabs using standard and widely available material testing equipment.

Bidirectional propagation of low frequency oscillations over the human hippocampal surface.

The hippocampus is diversely interconnected with other brain systems along its axis. Cycles of theta-frequency activity are believed to propagate from the septal to temporal pole, yet it is unclear how this one-way route supports the flexible cognitive capacities of this structure. We leveraged novel thin-film microgrid arrays conformed to the human hippocampal surface to track neural activity two-dimensionally in vivo.

A flexible 3-dimensional microelectrode array for in vitro brain models.

Three-dimensional (3D) in vitro models have become increasingly popular as systems to study cell-cell and cell-ECM interactions dependent on the spatial, mechanical, and chemical cues within the environment of the tissue, which is limited in traditional two-dimensional (2D) models. Although electrophysiological recordings of neuronal action potentials through 2D microelectrode arrays (MEAs) are a common and trusted method of evaluating neuronal function, network communication, and response to chemicals and biologicals, there are currently limited options for measuring electrophysiological activity from many locations simultaneously throughout a 3D network of neurons in vitro. Here, we have developed a thin-film, 3D flexible microelectrode array (3DMEA) that non-invasively interrogates a 3D culture of neurons and can accommodate 256 channels of recording or stimulation.

Binocular 3D otolith-ocular reflexes: responses of chinchillas to prosthetic electrical stimulation targeting the utricle and saccule.

From animal experiments by Cohen and Suzuki et al. in the 1960s to the first-in-human clinical trials now in progress, prosthetic electrical stimulation targeting semicircular canal branches of the vestibular nerve has proven effective at driving directionally appropriate vestibulo-ocular reflex eye movements, postural responses, and perception. That work was considerably facilitated by the fact that all hair cells and primary afferent neurons in each canal have the same directional sensitivity to head rotation, the three canals' ampullary nerves are geometrically distinct from one another, and electrically evoked three-dimensional (3D) canal-ocular reflex responses approximate a simple vector sum of linearly independent components representing relative excitation of each of the three canals.

Chronic Implantation of Multiple Flexible Polymer Electrode Arrays.

Simultaneous recordings from large populations of individual neurons across distributed brain regions over months to years will enable new avenues of scientific and clinical development. The use of flexible polymer electrode arrays can support long-lasting recording, but the same mechanical properties that allow for longevity of recording make multiple insertions and integration into a chronic implant a challenge. Here is a methodology by which multiple polymer electrode arrays can be targeted to a relatively spatially unconstrained set of brain areas.

Electrochemical Roughening of Thin-Film Platinum Macro and Microelectrodes.

This protocol demonstrates a method for electrochemical roughening of thin-film platinum electrodes without preferential dissolution at grain boundaries of the metal. Using this method, a crack free, thin-film macroelectrode surface with up to 40 times increase in active surface area was obtained. The roughening is easy to do in a standard electrochemical characterization laboratory and incudes the application of voltage pulses followed by extended application of a reductive voltage in a perchloric acid solution.

A microfabricated, 3D-sharpened silicon shuttle for insertion of flexible electrode arrays through dura mater into brain.

Objective: Electrode arrays for chronic implantation in the brain are a critical technology in both neuroscience and medicine. Recently, flexible, thin-film polymer electrode arrays have shown promise in facilitating stable, single-unit recordings spanning months in rats. While array flexibility enhances integration with neural tissue, it also requires removal of the dura mater, the tough membrane surrounding the brain, and temporary bracing to penetrate the brain parenchyma.

High-Density, Long-Lasting, and Multi-region Electrophysiological Recordings Using Polymer Electrode Arrays.

The brain is a massive neuronal network, organized into anatomically distributed sub-circuits, with functionally relevant activity occurring at timescales ranging from milliseconds to years. Current methods to monitor neural activity, however, lack the necessary conjunction of anatomical spatial coverage, temporal resolution, and long-term stability to measure this distributed activity. Here we introduce a large-scale, multi-site, extracellular recording platform that integrates polymer electrodes with a modular stacking headstage design supporting up to 1,024 recording channels in freely behaving rats.

A Fully Automated Approach to Spike Sorting.

Understanding the detailed dynamics of neuronal networks will require the simultaneous measurement of spike trains from hundreds of neurons (or more). Currently, approaches to extracting spike times and labels from raw data are time consuming, lack standardization, and involve manual intervention, making it difficult to maintain data provenance and assess the quality of scientific results. Here, we describe an automated clustering approach and associated software package that addresses these problems and provides novel cluster quality metrics.

Second spatial derivative analysis of cortical surface potentials recorded in cat primary auditory cortex using thin film surface arrays: Comparisons with multi-unit data.

Background: Current source density analysis of recordings from penetrating electrode arrays has traditionally been used to examine the layer- specific cortical activation and plastic changes associated with changed afferent input. We report on a related analysis, the second spatial derivative (SSD) of surface local field potentials (LFPs) recorded using custom designed thin-film polyimide substrate arrays.

Results: SSD analysis of tone- evoked LFPs generated from the auditory cortex under the recording array demonstrated a stereotypical single local minimum, often flanked by maxima on both the caudal and rostral sides.

Towards a large-scale recording system: demonstration of polymer-based penetrating array for chronic neural recording.

The brain is a massively interconnected network of specialized circuits. Even primary sensory areas, once thought to support relatively simple, feed-forward processing, are now known to be parts of complex feedback circuits. All brain functions depend on millisecond timescale interactions across these brain networks.

Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use.

Diffusion-bonded electrodes for chronic neural stimulation.

We report a novel method to fabricate chronic neural interfaces with the intent to combine the reliability and lifetime of bulk metal electrodes, with the miniaturization and mechanical flexibility of thin-film polymer microelectrode arrays. 10 μm thick platinum discs were laser cut from a foil into the shape of individual electrodes, and coated with gold on the backside. The discs were bonded to a microelectrode array with gold bond pads via gold-gold inter-diffusion using a flipchip bonder.

Insertion of flexible neural probes using rigid stiffeners attached with biodissolvable adhesive.

Microelectrode arrays for neural interface devices that are made of biocompatible thin-film polymer are expected to have extended functional lifetime because the flexible material may minimize adverse tissue response caused by micromotion. However, their flexibility prevents them from being accurately inserted into neural tissue. This article demonstrates a method to temporarily attach a flexible microelectrode probe to a rigid stiffener using biodissolvable polyethylene glycol (PEG) to facilitate precise, surgical insertion of the probe.

Microfabricated polymer-based neural interface for electrical stimulation/recording, drug delivery, and chemical sensing--development.

We present here a microfabricated, multi-functional neural interface with the ability to selectively apply electrical and chemical stimuli, while simultaneously monitoring both electrical and chemical activity in the brain. Such a comprehensive approach is required to understand and treat neuropsychiatric disorders, such as major depressive disorder (MDD), and to understand the mechanisms underlying treatments, such as pharmaceutical therapies and deep brain stimulation (DBS). The polymer-based, multi-functional neural interface is capable of electrical stimulation and recording, targeted drug delivery, and electrochemical sensing.

Improved chronic neural stimulation using high surface area platinum electrodes.

We report a novel nano-cluster platinum (NCPt) film that exhibits enhanced performance as an electrode material for neural stimulation applications. Nano-cluster films were deposited using a custom physical vapor deposition process and patterned on a flexible polyimide microelectrode array using semiconductor processing technology. Electrode performance was characterized in vitro using electrochemical impedance spectroscopy and compared with sputtered thinfilm platinum (TFPt) electrodes.

Polymer neural interface with dual-sided electrodes for neural stimulation and recording.

We present here a demonstration of a dual-sided, 4-layer metal, polyimide-based electrode array suitable for neural stimulation and recording. The fabrication process outlined here utilizes simple polymer and metal deposition and etching steps, with no potentially harmful backside etches or long exposures to extremely toxic chemicals. These polyimide-based electrode arrays have been tested to ensure they are fully biocompatible and suitable for long-term implantation; their flexibility minimizes the injury and glial scarring that can occur at the implantation site.

Optimization of multi-layer metal neural probe design.

We present here a microfabrication process for multi-layer metal, multi-site, polymer-based neural probes. The process has been used to generate 1-, 2-, and 4-layer trace metal neural probes with highly uniform and reproducible electrode characteristics. Typically, increasing the number of metal layers is assumed to both reduce the width of the neural probes and minimize the injury and glial scarring caused at the implantation site.

Removable silicon insertion stiffeners for neural probes using polyethylene glycol as a biodissolvable adhesive.

Flexible polymer probes are expected to enable extended interaction with neural tissue by minimizing damage from micromotion and reducing inflammatory tissue response. However, their flexibility prevents them from being easily inserted into the tissue. This paper describes an approach for temporarily attaching a silicon stiffener with biodissolvable polyethylene glycol (PEG) so that the stiffener can be released from the probe and extracted shortly after probe placement.

Caged neuron MEA: a system for long-term investigation of cultured neural network connectivity.

Traditional techniques for investigating cultured neural networks, such as the patch clamp and multi-electrode array, are limited by: (1) the number of identified cells which can be simultaneously electrically contacted, (2) the length of time for which cells can be studied, and (3) the lack of one-to-one neuron-to-electrode specificity. Here, we present a new device - the caged neuron multi-electrode array - which overcomes these limitations. This micro-machined device consists of an array of neurocages which mechanically trap a neuron near an extracellular electrode.

Parylene neurocages for electrical stimulation on silicon and glass substrates.

We present a refined method and design for building parylene neurocages for in vitro studies of live neural networks. Parylene neurocages are biocompatible and very robust, making them ideally suited for studying the synaptic connections between individual neurons to gain insight into learning and memory. The neurocage fabrication process incorporates electrodes into the neurocages to allow for stimulation and recording of action potentials.

Development of biocompatible parylene neurocages.

We present a refined method and design for building parylene neurocages for in vitro studies of live neural networks. Parylene neurocages are biocompatible and very robust, making them ideally suited for studying the synaptic connections between individual neurons to gain insight into learning and memory. The neurocage fabrication process is significantly less complex than earlier versions.